Endocrine Disruption

Front Neurol. 2026 Aug 14;17:1867856. doi: 10.3389/fneur.2026.1867856. eCollection 2026.

ABSTRACT

Neurodevelopmental and neurodegenerative disorders are related disorders lying on a spectrum of neural dysfunction with overlapping molecular and cellular mechanisms. Early-life diseases like autism spectrum disorder and attention-deficit/hyperactivity disorder are the result of disturbed neurodevelopment, while late-onset diseases such as Alzheimer's disease and Parkinson's disease are defined by progressive neuronal loss and loss of function. Emerging evidence shows that environmental exposures are important, modifiable factors that affect brain health throughout the lifespan. Factors such as air pollution, heavy metals, pesticides, and endocrine-disrupting chemicals act in combination with genetic susceptibility to disrupt neurogenesis, synaptic plasticity, and neuro-immune signaling. These exposures cause persistent epigenetic modifications, oxidative stress, mitochondrial dysfunction, and chronic neuro-inflammation, linking early developmental insults to neurodegenerative processes later in life. The concepts of the exposome and the developmental origins of health and disease provide additional support for the cumulative, lifelong impact of environmental interactions. Mechanistically, the recurrent process of neuronal damage is caused by impaired proteostasis, microglial stimulation, and blood-brain barrier dysfunction. Furthermore, the gut-brain axis is a hyperactive system in which immune responses and microbial metabolites trigger neurobiological responses to external stimuli. This review integrates multidisciplinary evidence to elucidate the mechanism and emphasizes environmental risk mitigation and translational strategies to reduce disease burden and promote lifelong brain resilience.

PMID:42666234 | PMC:PMC13521875 | DOI:10.3389/fneur.2026.1867856

Birth Defects Res. 2026 Sep;118(9):e70112. doi: 10.1002/bdr2.70112.

ABSTRACT

BACKGROUND: Childhood stunting (height-for-age z-score < -2 SD) remains a global developmental health burden. Traditional interventions centered on nutrition and infection have reached a bottleneck. Emerging evidence identifies chronic low-dose dietary environmental toxins as an independent, modifiable risk factor for early-life growth restriction.

METHODS: This review synthesizes cohort studies, meta-analyses, and in vivo toxicological models published over the past decade to characterize exposures to mycotoxins, toxic heavy metals, and food-borne endocrine disruptors that are closely associated with stunting.

RESULTS: Multi-layered mechanisms are elucidated, including environmental enteric dysfunction (EED), intestinal barrier disruption, persistent subclinical inflammation, GH-IGF-1 axis disturbance, gut microbiota dysbiosis, oxidative stress, and epigenetic alterations, which collectively impair linear growth. Critical surveillance gaps are identified, and integrated environment-nutrition-infection intervention strategies aligned with public health practice are proposed.

CONCLUSIONS: Dietary environmental toxins cause irreversible developmental deficits by damaging intestinal function and disrupting endocrine regulation. Strengthening developmental toxicology-oriented monitoring and source control will support precise prevention of early childhood stunting within the critical first 1000-day window.

PMID:42666064 | PMC:PMC13525387 | DOI:10.1002/bdr2.70112

J Environ Sci Health C Toxicol Carcinog. 2026 Aug 29:1-21. doi: 10.1080/26896583.2026.2722385. Online ahead of print.

ABSTRACT

This systematic review synthesized evidence on the health effects of microplastic exposure, with emphasis on organ-specific toxicity, molecular mechanisms, and implications for chronic disease. Following PRISMA 2020 guidelines, we searched PubMed, Scopus and Web of Science for peer-reviewed studies examining health outcomes associated with microplastic exposure relevant to bottled water consumption. Eligible studies included human observational studies, controlled animal experiments, and mechanistic in vitro investigations. Of 128 identified records, 15 studies met inclusion criteria: 3 human observational studies, 5 in vivo experiments, 4 in vitro investigations, and 3 mixed-design studies. Geographically, studies originated from China (40%), United States (20%), and other regions (40%). Polystyrene (10 studies), polyethylene, and polyethylene terephthalate (4 studies each) were most frequently investigated. Human biomonitoring confirmed microplastic presence in blood (3.15 ± 1.25 particles/mL), placental tissue (226-273 µg/g), and testicular samples (328 µg/g). Reproductive toxicity was the most consistently reported adverse outcome (5 studies), followed by hepatic, gastrointestinal, cardiovascular, renal, developmental, and neurological effects. Across studies, oxidative stress (reported in 12 studies), inflammatory activation (10 studies), endocrine disruption (4 studies), and mitochondrial dysfunction (4 studies) emerged as principal mechanistic pathways. Chronic exposure to microplastics from bottled water may contribute to multisystem toxicity through oxido-inflammatory mechanisms.

PMID:42667298 | DOI:10.1080/26896583.2026.2722385

J Environ Sci Health C Toxicol Carcinog. 2026 Aug 29:1-21. doi: 10.1080/26896583.2026.2722385. Online ahead of print.

ABSTRACT

This systematic review synthesized evidence on the health effects of microplastic exposure, with emphasis on organ-specific toxicity, molecular mechanisms, and implications for chronic disease. Following PRISMA 2020 guidelines, we searched PubMed, Scopus and Web of Science for peer-reviewed studies examining health outcomes associated with microplastic exposure relevant to bottled water consumption. Eligible studies included human observational studies, controlled animal experiments, and mechanistic in vitro investigations. Of 128 identified records, 15 studies met inclusion criteria: 3 human observational studies, 5 in vivo experiments, 4 in vitro investigations, and 3 mixed-design studies. Geographically, studies originated from China (40%), United States (20%), and other regions (40%). Polystyrene (10 studies), polyethylene, and polyethylene terephthalate (4 studies each) were most frequently investigated. Human biomonitoring confirmed microplastic presence in blood (3.15 ± 1.25 particles/mL), placental tissue (226-273 µg/g), and testicular samples (328 µg/g). Reproductive toxicity was the most consistently reported adverse outcome (5 studies), followed by hepatic, gastrointestinal, cardiovascular, renal, developmental, and neurological effects. Across studies, oxidative stress (reported in 12 studies), inflammatory activation (10 studies), endocrine disruption (4 studies), and mitochondrial dysfunction (4 studies) emerged as principal mechanistic pathways. Chronic exposure to microplastics from bottled water may contribute to multisystem toxicity through oxido-inflammatory mechanisms.

PMID:42667298 | DOI:10.1080/26896583.2026.2722385

Ecotoxicol Environ Saf. 2026 Aug 29;323:120737. doi: 10.1016/j.ecoenv.2026.120737. Online ahead of print.

ABSTRACT

Nonylphenol (NP) is an alkylphenol environmental contaminant with endocrine-disrupting activity and potential hepatotoxicity. However, the molecular responses associated with different NP exposure durations remain insufficiently characterized. In this study, male Kunming mice were exposed to NP through drinking water at 500 μg/L for 10 days (NP-S) or 90 days (NP-L) (n = 8/group), and hepatic toxicological alterations were evaluated using biochemical, histopathological, transcriptomic, metabolomic, and integrative analyses. Network toxicology analysis was first applied as a hypothesis-generating approach to identify candidate NP-associated hepatotoxicity targets. Most candidate targets had corresponding mouse orthologs. Compared with control mice, short-term NP exposure induced substantial transcriptional and metabolic alterations without significant changes in serum aminotransferases, oxidative stress markers, or liver histopathology. In contrast, long-term NP exposure was associated with increased ALT and AST activities, reduced SOD and GSH-Px activities, increased MDA levels, elevated IL-6 and IL-1β levels, and histopathological liver injury. Multi-omics analysis revealed that NP exposure affected pathways related to xenobiotic metabolism, glutathione metabolism, retinol metabolism, lipid remodeling, arachidonic acid metabolism, and inflammatory signaling. WGCNA identified exposure-associated co-expression modules, including an NP-L-associated module correlated with liver injury-related phenotypes. Targeted transcriptomic analysis further indicated coordinated alterations in estrogen receptor/nuclear receptor-related genes, CYP-mediated phase I metabolism, and GST/UGT-mediated phase II detoxification. Integrated transcriptome-metabolome analysis suggested coordinated remodeling of xenobiotic metabolism, oxidative stress, lipid metabolism, and inflammatory responses. Overall, under the present single-dose mouse exposure design, short- and long-term NP exposure were associated with distinct hepatic molecular and toxicological profiles. These findings suggest that early molecular reprogramming may precede overt hepatic injury, whereas prolonged exposure is associated with broader metabolic disturbance and more evident liver toxicity.

PMID:42667705 | DOI:10.1016/j.ecoenv.2026.120737

Environ Pollut. 2026 Aug 29:129026. doi: 10.1016/j.envpol.2026.129026. Online ahead of print.

ABSTRACT

Bisphenol A (BPA), an endocrine-disrupting chemical, is widely used in plastics and resins. It migrates into food and drinking water from food contact material and is also released into environmental media such as air and dust. Consequently, human exposure occurs not only via dietary intake but also through dermal contact and inhalation. We conducted an aggregated exposure assessment by integrating dietary and non-dietary exposure sources. Dietary exposure was estimated based on BPA concentration data from our nationwide survey and food consumption data from the China Food Consumption Surveys. Dietary exposure for exclusively breastfed infants was assessed based on scenario assumptions and data from the literature. Non-dietary exposure incorporated sources from environmental media (air, dust) and consumer products such as toys, skincare products, and thermal paper, mainly using data retrieved from the literature. In 14 age-gender groups, the mean and 95th percentile (P95) dietary exposure levels ranged from 145.39 to 332.47 ng/kg BW and 300.00 to 706.61 ng/kg BW, respectively; the mean and P95 aggregated exposure levels ranged from 157.98 to 432.04 ng/kg BW and 332.04 to 1661.79 ng/kg BW, respectively. Both the dietary and aggregated exposure levels were lower than the temporary tolerable daily intake (4 μg/kg BW) previously established, suggesting a low health risk of dietary BPA exposure and a low level of aggregated BPA exposure in the population of China. Therefore, based on current exposure levels, BPA is not a priority concern for public health in China.

PMID:42668130 | DOI:10.1016/j.envpol.2026.129026

J Steroid Biochem Mol Biol. 2026 Aug 28:107107. doi: 10.1016/j.jsbmb.2026.107107. Online ahead of print.

ABSTRACT

Estrone (E1), a ubiquitous environmental estrogen, poses a potential threat to the reproductive health of aquatic organisms. To evaluate the inducing effect of E1 exposure on gonadal feminization in male Siniperca chuatsi, male fish were exposed to 0, 0.01, 0.1, and 1μg/L E1 for 60 days. The effects of E1 exposure on serum sex hormones, gonadal histological sections, vasa in situ hybridization, cell apoptosis, and gene expression in S. chuatsi were systematically examined. The results showed that 0.1μg/L E1 treatment significantly inhibited testicular germ cell development, while 1μg/L E1 treatment induced gonad histological feminization in 80% of male fish, with early vitellogenic oocytes appeared. Additionally, E1 exposure caused significant changes in serum sex hormones: 11-ketotestosterone levels significantly decreased, while immunoreactive estradiol levels significantly increased. Vasa gene in situ hybridization showed positive signals and TUNEL cell apoptosis revealed no obvious apoptotic signals in E1-induced histologically feminized gonads. Further molecular analysis revealed that sex regulation and development-related genes were involved in the E1-mediated gonadal feminization process: the expression of key male sex determination genes (dmrt1, amh, gsdf, sox9) and steroidogenic support genes (star, fshr) was significantly down-regulated, while expression of key female differentiation genes (bmp15, foxl2, cyp19a1a, hsd17b1) and germ cell development genes (sox19a, dazl, vasa, ccne2, sox3) was significantly up-regulated. Collectively, these findings demonstrate that E1 exposure induces histological testicular feminization in male S. chuatsi in a dose-dependent manner, concomitant with transcriptional downregulation of male differentiation genes and upregulation of female differentiation genes.

PMID:42665132 | DOI:10.1016/j.jsbmb.2026.107107

Food Chem Toxicol. 2026 Aug 28:116349. doi: 10.1016/j.fct.2026.116349. Online ahead of print.

ABSTRACT

Methylparaben (MP) is a widely used preservative with potential endocrine-disrupting activity, but its role in colorectal cancer (CRC) remains unclear. This study integrated in vitro and in vivo experiments with transcriptomics, network toxicology, and molecular simulations to investigate MP's effects on CRC progression. MP enhanced CRC cell proliferation, migration, and epithelial-mesenchymal transition while suppressing apoptosis in vitro. In CT26 tumor-bearing mice, dietary MP accelerated tumor growth and induced a pro-inflammatory microenvironment. Transcriptomic and network toxicology analyses implicated nuclear receptor signaling and inflammatory pathways. Among eight core targets identified, CD209 exhibited the most stable MP binding and was functionally validated in vivo: CD209a blockade significantly attenuated MP-driven tumor growth, reduced proliferation, and restored apoptosis. These findings demonstrate that MP promotes CRC through coordinated nuclear receptor and inflammatory signaling, with CD209 as a critical mediator, providing mechanistic insights for environmental risk assessment of chronic MP exposure.

PMID:42665206 | DOI:10.1016/j.fct.2026.116349

Mol Divers. 2026 Aug 28. doi: 10.1007/s11030-026-11712-1. Online ahead of print.

ABSTRACT

Breast cancer (BC) represents a major public-health burden, and epidemiological evidence suggests a potential association with exposure to methyl 4-hydroxybenzoate (MEP), a widely-used cosmetic preservative and estrogen-mimicking endocrine-disrupting chemical. Nevertheless, the potential mechanisms underlying MEP-associated BC oncogenesis and progression remain poorly understood. BC-related targets were curated from CTD, GeneCards, and OMIM, whereas MEP-related targets were interrogated from ChEMBL, PharmMapper, and SEA using stringent filters. The intersecting targets informed subsequent protein-protein interaction network construction and molecular docking studies. Subsequently, consensus molecular subtypes of BC were derived by applying ten clustering algorithms to multi-omics data, which were subsequently employed in three machine learning algorithms to develop a consensus MEP-related signature (CMEPRS) for BC patients. Five core putative toxicological targets (HSP90AA1, CTNNB1, TP53, MYC, and EGFR) with critical regulatory roles in MEP-associated molecular alterations were identified. Based on these findings, we generated MEP-toxicity-related classifiers and the CMEPRS prognostic model, which may facilitate patient stratification and support personalized clinical management for BC patients. The high-CMEPRS patients displayed prominent infiltration of macrophages, myeloid-derived suppressor cells, and cancer-associated fibroblasts. Apart from lapatinib, the high-CMEPRS patients showed higher predicted sensitivity to most conventional chemotherapeutic drugs. This computational study provides preliminary insights into molecular alterations linked to MEP exposure and offers a feasible analytical framework for patient stratification and therapeutic-target exploration in breast cancer.

PMID:42665765 | DOI:10.1007/s11030-026-11712-1

Curr Biol. 2026 Aug 28:S0960-9822(26)00933-4. doi: 10.1016/j.cub.2026.07.034. Online ahead of print.

ABSTRACT

Reproductive behaviors are critical to the sustainability of wild fish populations and are threatened by the presence of potent endocrine-disrupting chemicals.^1,2,3 Laboratory studies have routinely shown that key behaviors (e.g., nesting and aggression) of male fish are reduced following exposure to hormone mimics,^4,5,6,7 yet the applicability of these findings to nature and consequences for wild populations are unknown. Here, we quantified, in situ, the reproductive behavior of male fathead minnows (Pimephales promelas) before, during, and after (spanning 12 years in total) a 3-year period in which the synthetic estrogen, ethinylestradiol (EE2, ∼5 ng/L) was added to an experimental lake, while also recording fish in nearby unmanipulated reference lakes.^8,9 In contrast to expectations, nesting males showed heightened aggression during the exposure period that was triggered by the unexpected presence of more conspecifics at nest sites. Consequently, paternal care became more fragmented, males spent less time at the nest, and they had fewer eggs in their nests. These altered breeding dynamics, including marked reductions in male secondary sexual characteristics, contributed to a population collapse during EE2 amendments. Our findings underscore that social interactions in natural systems provide a challenging but necessary arena in which to pursue ecotoxicological studies if we are to understand whether risk assessments meaningfully protect wild populations.

PMID:42664962 | DOI:10.1016/j.cub.2026.07.034

Environ Int. 2026 Aug 25;215:110477. doi: 10.1016/j.envint.2026.110477. Online ahead of print.

ABSTRACT

BACKGROUND: Benzophenones (BPs), widely used UV filters and endocrine disruptors globally known for their estrogenic effects, are raising growing concerns about chronic reproductive toxicity in males due to their increasing environmental concentrations. This study aims to reveal the effects and mechanisms of male reproductive injury induced by environmentally relevant concentrations of BPs exposure.

METHODS: The study employed NHANES analysis, animal experiments, cell experiments, network toxicology, and molecular docking, and used transcriptome sequencing along with various biochemical and molecular experimental methods to measure downstream indicators.

RESULTS: Analysis of the NHANES database indicates that BP-3 exposure showed dose-dependent associations with reduced total testosterone (TT)/estradiol (E2)/sex hormone-binding globulin (SHBG) and elevated testosterone deficiency (TD) risk. Effects attenuated but held direction after multi-pollutant adjustment. The results of animal experiments indicate that chronic exposure to BPs (PND1-PND240) impaired fertility and offspring development, reduced body weight, anogenital distance, and testis coefficient, and altered histopathology, sperm quantity, and quality. Differentially expressed genes were predominantly enriched in energy metabolism and integrity of actin cytoskeleton, and disulfidptosis-related metabolic/redox indicators were dysregulated in the testis. Notably, even short-term exposure to BP-3 disturbs the levels of disulfidptosis-associated metabolic drivers (PND1-PND56). In GC-2 cells, BP-3 reduced cell viability and antioxidant capacity, induced morphological alterations, elevated ROS level, and upregulated disulfidptosis markers. The involvement of disulfidptosis was confirmed by the addition of the antagonist TCEP and agonist KL-11743. Notably, estrogen receptor (ER) directly regulates disulfidptosis. Zeaxanthin dipalmitate (ZD) alleviates BPs-induced male reproductive injury by modulating disulfidptosis. Co-culture assays further confirmed BP-3 disrupts testicular metabolic coupling and triggers disulfidptosis.

CONCLUSION: BPs exposure induces male reproductive dysfunction via ER-mediated disulfidptosis. ZD can alleviate this dysfunction.

PMID:42664869 | DOI:10.1016/j.envint.2026.110477

Front Endocrinol (Lausanne). 2026 Aug 13;17:1820034. doi: 10.3389/fendo.2026.1820034. eCollection 2026.

ABSTRACT

Acromegaly is a rare endocrine disorder characterized by chronic growth hormone (GH) hypersecretion, usually due to a pituitary neuroendocrine tumor, leading to persistently elevated insulin-like growth factor 1 (IGF-1) levels. Although improved biochemical control reduces complications, cancer-related mortality remains a growing concern. Patients with acromegaly exhibit an increased prevalence of colorectal neoplasia, likely driven by sustained GH/IGF-1-mediated epithelial proliferation, reduced apoptosis, and activation of pro-tumorigenic signaling pathways. Concurrently, gut microbiota has emerged as a key modulator of intestinal homeostasis and carcinogenesis. Dysbiosis contributes to colorectal cancer development through chronic inflammation, production of genotoxins, disruption of epithelial barrier, and altered microbial metabolite profiles, including reduced short-chain fatty acids (SCFAs). Increasing evidence supports a bidirectional relationship between the gut microbiota and the GH/IGF-1 axis: microbial composition and SCFAs production can influence systemic and local IGF-1 levels, while GH and IGF-1 modulate microbial diversity, intestinal barrier function, and immune responses. Recent studies suggest that acromegalic patients display distinct oral and fecal microbial signatures, characterized by reduced alpha diversity, altered Firmicutes/Bacteroidetes ratio, and increased abundance of taxa potentially associated with colorectal carcinogenesis. Although causality has not been established, these alterations may interact with hormonal excess, insulin resistance, and systemic inflammation to create a permissive microenvironment for neoplastic transformation. This review provides an integrated clinical and pathophysiological synthesis of current evidence linking acromegaly, gut microbiota alterations, and colorectal cancer risk. Understanding this complex interplay may refine colorectal cancer risk stratification and open avenues for microbiota-targeted preventive or therapeutic strategies alongside endocrine disease control.

PMID:42662354 | PMC:PMC13519515 | DOI:10.3389/fendo.2026.1820034

Int J Gen Med. 2026 Aug 23;19:623192. doi: 10.2147/IJGM.S623192. eCollection 2026.

ABSTRACT

BACKGROUND: The global burden of kidney stones is increasing, while di(2-ethylhexyl) phthalate (DEHP), a widespread plasticizer and endocrine-disrupting pollutant, has been implicated as a potential environmental risk factor. This study investigated the mechanisms by which DEHP may aggravate calcium oxalate kidney stones through network toxicology, computational analyses, and experimental validation.

METHODS: DEHP- and kidney stone-related targets were retrieved from six databases. Shared targets were analyzed using protein-protein interaction networks and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Molecular docking and 100-ns molecular dynamics simulations were performed to evaluate interactions between DEHP and hub proteins. A glyoxylic acid-induced mouse model and calcium oxalate monohydrate (COM)-challenged HK-2 cells were used to assess the effects of DEHP on crystal deposition, renal injury, apoptosis, and autophagy.

RESULTS: A total of 457 shared targets were identified, with CTNNB1, SRC, HSP90AA1, EP300, EGFR, and TP53 emerging as hub genes. Computational analyses suggested stable interactions between DEHP and these proteins and highlighted cell fate-related pathways, including PI3K-Akt signaling, autophagy, and apoptosis. In vivo, DEHP increased blood urea nitrogen and serum creatinine levels, aggravated tubular injury, and enhanced calcium oxalate crystal deposition. Consistent effects were observed in COM-treated HK-2 cells, accompanied by dysregulation of apoptosis- and autophagy-related markers.

CONCLUSION: DEHP aggravates calcium oxalate crystal-induced renal injury and promotes kidney stones, potentially by disrupting apoptosis-autophagy homeostasis in renal tubular epithelial cells. These findings provide mechanistic evidence linking DEHP exposure to kidney stone pathogenesis.

PMID:42662485 | PMC:PMC13520968 | DOI:10.2147/IJGM.S623192

Obes Pillars. 2026 Aug 14;19:100321. doi: 10.1016/j.obpill.2026.100321. eCollection 2026 Sep.

ABSTRACT

BACKGROUND: Obesity prevalence among females in the United States continues to rise across the lifespan, imposing a substantial burden on individuals and the health care system through an increasing number of preventable, excess weight-attributable disabling diseases and mortality. A clearer understanding of the impact of obesity and treatment interventions on outcomes for reproduction, cardiometabolic risk, musculoskeletal health, and mental health at various life stages is critical to optimizing management strategies for women with obesity.

METHODS: This narrative clinical review synthesizes published literature and expert perspectives regarding obesity-related risk factors, health outcomes, and treatment considerations related to obesity in women, including the impact of obesity medications across the lifespan.

RESULTS: Adiposity influences reproductive, cardiometabolic, musculoskeletal, and mental health outcomes across the female lifespan. During adolescence, early pubertal onset and metabolic dysfunction are common. In reproductive years, infertility, polyendocrine metabolic ovarian syndrome, and pregnancy complications are prominent. Perimenopause is associated with vasomotor symptoms, sleep disruption, and increased cardiovascular risk. In older age, risks for cancer, functional decline, and frailty increase. Pharmacologic therapies, including incretin-based agents, demonstrate efficacy in weight reduction and cardiometabolic improvement, although life stage-specific safety and outcome data remain limited.

CONCLUSION: Obesity management in women requires individualized, life stage-specific approaches integrating lifestyle interventions and pharmacotherapy. Additional research is needed to clarify long-term outcomes and optimize treatment strategies across the lifespan.

PMID:42662578 | PMC:PMC13521148 | DOI:10.1016/j.obpill.2026.100321

Horm Behav. 2026 Aug 28;185:105983. doi: 10.1016/j.yhbeh.2026.105983. Online ahead of print.

ABSTRACT

Thyroid hormones regulate embryonic and fetal neurodevelopment, with the maternal thyroid gland exclusively producing these hormones for the first half of gestation and then a combination of maternal and fetal production occurring during the second half of gestation. Hypothyroidism during pregnancy is common in humans, particularly due to the additional demand put on the thyroid gland as pregnancy proceeds. Epidemiological studies have linked maternal hypothyroidism to an increased risk of attention-deficit/hyperactivity disorder and autism spectrum disorder diagnosis in these children, as well as cognitive deficits and delays. Rodent models have been extensively used to model developmental hypothyroidism and study the long-term effects on offspring. Increases in activity, reductions in anxiety, cognitive impairments, and social alterations have been observed. In this review, I discuss the current understanding of the organizational impacts of hypothyroidism on activity, affective behaviors, cognition, and social behaviors in humans and animal models, paying special attention to critical periods that may underlie these effects. I also review potential interactions between thyroid hormones and steroid hormones known to be important for organization of the brain and behavior during perinatal and adolescent development. Understanding the effects of developmental hypothyroidism is critical, as early developmental exposure to many endocrine-disrupting chemicals may alter behavior through reducing thyroid hormone signaling, and the final section of the paper reviews these interactions. Understanding the organizational effects of thyroid hormones is important for decisions related to screening and interventions during pregnancy.

PMID:42664597 | DOI:10.1016/j.yhbeh.2026.105983

Food Chem. 2026 Aug 26;527:150907. doi: 10.1016/j.foodchem.2026.150907. Online ahead of print.

ABSTRACT

Total Diet Studies (TDSs) provide data on the occurrence of substances in commonly consumed foods for dietary exposure assessment. We present data from the BfR MEAL Study, the first full-scale German TDS, for the determination of plasticizers and additives in 226 pooled food samples. A multi-technique approach with matrix-dependent sample preparation, which was comprehensively validated in seven representative food matrices, was applied to the samples of various types of food matrices. This approach features high precision, recovery, and sensitivity, enabling reliable determination of 60 target analytes in all types of food collected in this study. In all samples, at least one of the analytes was detected, and in the majority of samples, at least one of the analytes could be quantified. The content of the ortho-phthalate plasticizers connected to reproductive toxicity and endocrine disrupting properties in the samples was low in most cases. A median of weighed overall content of hazardous phthalates (DEHP, DIBP, DNBP, BBP, DINP) of 15.3 μg DEHP equivalents/kg food suggests that overall exposure would be well below the TDI of 50 μg DEHP equivalents/kg bw/day. Detection frequency and content of some alternative plasticizers and additives were higher (e.g., up to 23,000 and 1300 μg/kg food for DINCH and DEHA). However, the median concentrations of these analytes were much lower: 99 and 56 μg/kg food.

PMID:42664845 | DOI:10.1016/j.foodchem.2026.150907

Front Immunol. 2026 Aug 12;17:1838242. doi: 10.3389/fimmu.2026.1838242. eCollection 2026.

ABSTRACT

The plasticizer butyl benzyl phthalate (BBP), a ubiquitous endocrine disruptor, is commonly used in PVC products and can leach into the environment, leading to human exposure. BBP has been detected in the placenta, amniotic fluid, and breast milk, indicating potential exposure during gestation and lactation. BBP is an endocrine disruptor compound (EDC) with estrogenic and anti-androgenic activity, which, at high or acute doses, may interfere with the development of hormone-dependent systems, including components of the neuro-immune-endocrine network (NIE) and sexual dimorphism. This study aimed to investigate the effects of perinatal BBP exposure on various components of the NIE network in adult male and female rats. Pregnant rats were administered drinking water with or without BBP (50 μg/L) from gestational day 5 until weaning. Offspring were assessed at 9 weeks of age by examining sex hormone levels in serum, immune cell populations in the spleen, neurotransmitters in the hippocampus, and cytokines in serum, hippocampus, and spleen. Results showed that BBP exposure led to lower weaning weights in both sexes, with persistent effects in males. Splenic T and T-helper lymphocyte populations increased in both sexes. In the hippocampus, females exhibited elevated proinflammatory cytokines, while males showed decreased serotonin levels, indicating sex-specific alterations in hormone, cytokine, and neurotransmitter levels in adult offspring.

PMID:42656255 | PMC:PMC13506368 | DOI:10.3389/fimmu.2026.1838242

Front Endocrinol (Lausanne). 2026 Aug 12;17:1829662. doi: 10.3389/fendo.2026.1829662. eCollection 2026.

ABSTRACT

BACKGROUND: Neonicotinoids (NEOs) are widely used pesticides with potential endocrine-disrupting properties, yet their distribution in human reproductive matrices and associations with male reproductive hormones remain unclear.

METHODS: We analyzed 146 paired semen and urine samples to characterize the distribution of 14 NEOs and their metabolites (m-NEOs) and to examine associations with male reproductive hormones. Concentrations were compared across matrices, and associations with follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), prolactin (PRL), estradiol (E₂), and the T/LH ratio were evaluated using exposome-wide association (EWAS), deletion-substitution-addition (DSA), and mixture models.

RESULTS: Detection frequencies ranged from 43.2% to 100% in urine and 19.9% to 99.3% in semen, with Desnitro-dinotefuran (DN) and Desmethyl-acetamiprid (DM-ACE) predominant in urine and DN and Acetamiprid (ACE) enriched in semen. Partitioning analysis revealed three distinct compound clusters: (1) DN, ACE, and Imidacloprid-urea (IMI-urea) enriched in semen; (2) Dinotefuran-urea (UF), Imidacloprid (IMI), Imidaclothiz (IMIT), and 5-Hydroxy-imidacloprid (5-OH-IMI); and (3) DM-ACE, Desnitro-imidacloprid (DN-IMI), Desnitro-imidacloprid-olefin (DN-IMI-olefin), and Clothianidin (CLO) predominantly excreted in urine. In EWAS and DSA, several nominal associations with hormones were observed. Nominal associations were observed between seminal CLO and FSH, DN and E₂, and urinary UF and LH, Thiacloprid (THCP) exposure showed nominal positive associations with PRL and E₂. However, none remained significant after correction for multiple testing. Mixture models indicated no overall significant associations. Sensitivity analyses supported the robustness of key compound-hormone associations.

CONCLUSION: NEOs and m-NEOs show distinct partitioning patterns between urine and semen, suggesting differential tissue distribution. Although several nominal associations with reproductive hormones were identified, none remained statistically significant after multiple-testing correction, indicating that these findings should be considered hypothesis-generating rather than conclusive. Further studies with larger populations and repeated measurements are needed to validate these associations and clarify the reproductive implications of NEO exposure in men.

PMID:42656286 | PMC:PMC13506491 | DOI:10.3389/fendo.2026.1829662

Int J Womens Health. 2026 Aug 21;18:621813. doi: 10.2147/IJWH.S621813. eCollection 2026.

ABSTRACT

INTRODUCTION: High-Intensity Sweeteners (HISs) are widely consumed as calorie-free sugar substitutes, particularly among girls and women of reproductive age. Despite their regulatory approval, growing evidence suggests potential endocrine-disrupting properties that may negatively impact women's reproductive health.

OBJECTIVE: This narrative review synthesizes human and animal evidence on the Potential Pathological Effects of AS on puberty onset and menstrual health, while elucidating the underlying biological mechanisms.

METHODS: A structured search of references in PubMed, Scopus, Web of Science, and Embase up to 2025 was conducted, prioritizing studies from 2015 onwards. Inclusion criteria required quantitative measurements of AS exposure and reproductive endpoints in non-pregnant, non-lactating women, or relevant animal models. Seventeen studies (12 animals, 5 humans) were thematically synthesized.

RESULTS: Chronic exposure to AS specifically aspartame, sucralose, saccharin, and acesulfame-K-disrupts female reproductive physiology through composition-dependent and developmentally timed mechanisms. These mechanisms include (1) suppression of the hypothalamic-pituitary-gonadal (HPG) axis through downregulation of Kiss1; (2) ovarian mitochondrial dysfunction, oxidative stress, and follicular atresia; and (3) reduced estrogen production by the gut microbiota through disruption of the estrobulum. Importantly, these effects often occur independently of body weight or metabolic changes. Human data have linked maternal and prepubescent AS consumption to premature thelarche, menstrual irregularities, and altered rate of puberty, particularly in carriers of TAS1R2/TAS1R3 polymorphisms. It is noteworthy that not all sweeteners pose the same risk: advantame and glycyrrhizin show neutral or protective profiles.

CONCLUSION: Artificial sweeteners may not be harmless, especially above the acceptable daily intake (ADI), and they could act as bioactive endocrine disruptors. However, given that much of the current evidence derives from animal studies and limited observational human data, further well-designed human studies are needed to confirm these associations and clarify their clinical significance.

PMID:42657207 | PMC:PMC13508044 | DOI:10.2147/IJWH.S621813

Biomed Res Int. 2026;2026(1):e5121993. doi: 10.1155/bmri/5121993.

ABSTRACT

BACKGROUND: Aflatoxin B1 (AFB1) is one of the most potent naturally occurring mycotoxins and has been implicated in reproductive toxicity. The present study is aimed at evaluating the time-dependent effects of experimental AFB1 exposure on ovarian follicular dynamics, reproductive hormone profiles, and intrinsic apoptosis-related markers in female rats.

METHODOLOGY: Twenty-four mature female Wistar rats were assigned to control and AFB1-exposed groups (N = 6 per time point). AFB1 was administered intraperitoneally at 20 mg/kg body weight for 7, 14, and 21 days. Ovarian tissue and serum samples were collected at the end of each designated exposure period. Follicular population and atresia were evaluated histologically; serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen, and progesterone were measured by ELISA, and the expression patterns of Bcl-2, Bax, p53, and caspase-3 were assessed using RT-PCR and immunohistochemistry.

RESULTS: AFB1 exposure was associated with a time-dependent reduction in total follicular population and a marked increase in follicular atresia. Serum FSH, LH, estrogen, and progesterone concentrations were significantly decreased in AFB1-exposed animals compared with controls. At the molecular level, AFB1 decreased Bcl-2 expression while increasing Bax, p53, and caspase-3 expression in ovarian tissue, with prominent immunoreactivity in follicular cells.

CONCLUSION: These findings indicate that experimental AFB1 exposure is associated with impaired follicular development, endocrine disruption, and activation of intrinsic apoptosis-related signaling in rat ovaries. The observed coordinated changes suggest a biologically plausible interaction between hormonal imbalance and apoptosis-associated pathways in AFB1-induced follicular atresia, although functional validation is required to confirm direct causal mechanisms.

PMID:42657948 | PMC:PMC13520782 | DOI:10.1155/bmri/5121993

FASEB J. 2026 Sep 15;40(17):e72224. doi: 10.1096/fj.202600392R.

ABSTRACT

Histidine methylation is an evolutionarily conserved but poorly understood post-translational modification. METTL18 is known to catalyze histidine Nτ-methylation in vitro, yet its physiological functions in mammals remain unclear. Here we show that mouse METTL18 possesses conserved histidine Nτ-methyltransferase activity and that its genetic deletion results in widespread effects on developmental, metabolic, and endocrine function. Mettl18 knockout (KO) embryos exhibit impaired growth with disruption of the transferrin-transferrin receptor (Trf-Tfrc) axis, suggesting insufficient fetal iron handling. After birth, Mettl18 KO mice remain underweight and show reduced liver and white adipose tissue mass. Moreover, Mettl18 KO mice exhibit decreased plasma and liver triglycerides, elevated adiponectin and improved glucose tolerance, indicative of a coordinated shift toward an energy-conserving metabolic Trf-Tfrc state. Notably, METTL18 deficiency impairs IGF-1-mediated signaling and suppresses the TSH-T4 axis, two major endocrine pathways critical for postnatal growth. Taken together, our results indicate that METTL18 functions as a conserved histidine methyltransferase that contributes to fetal development, endocrine regulation, and systemic metabolism, thereby influencing organismal growth in mammals.

PMID:42658657 | PMC:PMC13521299 | DOI:10.1096/fj.202600392R

Chem Biol Interact. 2026 Aug 27:112321. doi: 10.1016/j.cbi.2026.112321. Online ahead of print.

ABSTRACT

BACKGROUND: Bisphenol A (BPA) is a common environmental endocrine disruptor linked to type 2 diabetes mellitus (T2DM) and colorectal cancer (CRC), but the exact mechanism connecting BPA exposure to their comorbidity is unclear.

METHODS: This study integrated network toxicology, single-cell transcriptomic data, molecular simulation, in vitro cell experiments, and patient-derived explant (PDE) models to systematically explore the potential molecular basis underlying the correlation between BPA exposure and T2DM-CRC comorbidity.

RESULTS: CXCL8 was identified as the sole overlapping gene shared among the 30 BPA-T2DM-CRC common targets, the PPI-derived hub genes, and the DEGs identified in GSE115313. It was upregulated in T2DM-CRC tissues, associated with obesity and T2DM, and showed strong diagnostic performance in CRC (AUC=0.895). Immune analysis indicated an increased proportion of Tregs in CRC samples from patients with T2DM, while CXCL8 expression correlated positively with M1 macrophage and activated mast cell infiltration. Single-cell transcriptomic data analysis of GSE188711 showed that CXCL8 expression varied along the inferred pseudotime trajectory and appeared enriched in the annotated B-cell population. Molecular simulations showed moderate binding between BPA and CXCL8 (binding energy: -5.7 kcal/mol). BPA treatment boosted CRC cell proliferation, migration, and invasion, while CXCL8 knockdown reduced these activities. The malignant effects of BPA were significantly reduced when CXCL8 was knocked down. Mechanistically, TEAD4 was identified as a potential upstream transcriptional regulator of CXCL8, while increased CXCL8 expression was accompanied by enhanced p38 MAPK pathway activation.

CONCLUSIONS: BPA-induced CXCL8 upregulation is associated with CRC malignant progression and enhanced p38 MAPK signaling. TEAD4 may function as an upstream transcriptional regulator of CXCL8, although its direct regulation by BPA remains unclear. Given the clinical correlation between CXCL8 upregulation and T2DM status, this pathway may represent a potential mechanistic link contributing to the frequently observed T2DM-CRC comorbidity.

PMID:42660439 | DOI:10.1016/j.cbi.2026.112321

Medicina (Kaunas). 2026 Aug 17;62(8):1577. doi: 10.3390/medicina62081577.

ABSTRACT

Background and Objectives: Endometriosis is associated with chronic inflammation, immune dysregulation, oestrogen-dependent growth, oxidative stress, altered steroid hormone metabolism, compromised epithelial barrier integrity, and the production of bioactive microbial metabolites. These interconnected alterations have been proposed to create, in principle, a permissive local microenvironment for malignant transformation. This narrative review examines whether endometriosis-associated dysregulation of the gut and reproductive tract microbiota may act as a hypothetical biological modulator linking these multi-axis changes to endometrial carcinogenesis, with attention to immunological, endocrine, metabolic, microbial-metabolite, oxidative, and barrier-related pathways. Material and Methods: We narratively integrated current evidence on gut and reproductive tract microbiota alterations relevant to endometrial homeostasis, with emphasis on the estrobolome, low-biomass uterine microbial communities, inflammatory and immune signaling, microbial metabolites, and pathways implicated in carcinogenesis. Results: Available data suggest that dysbiosis may influence endometrial carcinogenesis through interconnected endocrine, inflammatory, metabolic, and immune mechanisms. Attention has been given to loss of Lactobacillus dominance, enrichment of anaerobic and pro-inflammatory taxa, altered estrogen recirculation, progesterone resistance, Toll-like receptor activation, NF-κB/STAT3 signaling, COX-2/PGE2 activity, PI3K/AKT/mTOR pathway activation, oxidative stress, macrophage polarization, and impaired natural killer cell surveillance. These alterations may contribute to a permissive microenvironment characterized by persistent inflammation, defective immune control, and disrupted endometrial homeostasis. However, the current literature remains limited by small and heterogeneous cohorts, predominantly cross-sectional designs, contamination risk, and marked methodological variability, particularly in low-biomass uterine samples. Conclusions: Current evidence supports the view that microbiome dysregulation is a context-dependent biological modulator that intersects with endocrine, inflammatory, metabolic, immune, oxidative, and barrier-related pathways relevant to endometrial carcinogenesis. Microbiome dysbiosis should be regarded as a hypothetical contributory factor rather than as an established causal driver. Its near-term translational relevance appears greater for biomarker development and risk stratification than for immediate microbiome-directed therapy. Longitudinal, standardized, and functionally integrated studies are needed to clarify whether microbiome-associated signatures can be translated into clinically meaningful prevention and management strategies in endometrial cancer.

PMID:42654474 | PMC:PMC13515978 | DOI:10.3390/medicina62081577

Medicina (Kaunas). 2026 Jul 25;62(8):1445. doi: 10.3390/medicina62081445.

ABSTRACT

Obesity is a multifactorial condition that profoundly affects female reproductive health through endocrine, metabolic, and inflammatory mechanisms that disrupt the hypothalamic-pituitary-gonadal (HPG) axis. Women with obesity frequently develop menstrual irregularities, anovulation, amenorrhea, infertility, polycystic ovary syndrome (PCOS), impaired endometrial receptivity, and adverse pregnancy outcomes. Central obesity and insulin resistance contribute to hyperinsulinemia, reduced sex hormone-binding globulin (SHBG) levels, hyperandrogenism, altered gonadotropin secretion, and impaired folliculogenesis, while adipokines such as leptin and chronic inflammation further impair ovarian steroidogenesis and ovulatory function. Obesity-related oxidative stress and lipotoxicity also negatively affect oocyte quality, embryo development, implantation, and assisted reproductive technology outcomes, increasing the risk of gestational diabetes, preeclampsia, miscarriage, and preterm birth. This review evaluates the therapeutic potential of pharmacological weight-loss therapies in obesity-associated female reproductive dysfunction. A comprehensive literature review was conducted using various databases, focusing on anti-obesity pharmacotherapy on obesity, infertility and fertility in reproductive-aged women. Evidence suggests that several FDA-approved and off-label anti-obesity agents, including orlistat, liraglutide, semaglutide, phentermine/topiramate, bupropion/naltrexone, metformin, exenatide, and tirzepatide, may improve reproductive outcomes primarily indirectly through weight reduction and metabolic improvement. GLP-1 receptor agonists, particularly liraglutide, semaglutide, and exenatide, appear especially promising, demonstrating beneficial effects on insulin sensitivity, menstrual regularity, ovulation, androgen levels, and pregnancy rates in women with PCOS. Tirzepatide, a dual GLP-1/GIP receptor agonist, has shown potent weight-loss and metabolic effects with potential indirect fertility benefits. Metformin improves insulin sensitivity and is widely used in PCOS to regulate androgen levels and restore ovulation, although its effects on pregnancy and live birth rates remain controversial. However, evidence for several agents remains limited, and concerns persist regarding reproductive safety during pregnancy. Overall, anti-obesity pharmacotherapy may represent an important adjunctive strategy for improving reproductive and metabolic health in women with obesity, although larger randomized clinical trials are still required.

PMID:42654342 | PMC:PMC13515260 | DOI:10.3390/medicina62081445

Biology (Basel). 2026 Aug 7;15(16):1337. doi: 10.3390/biology15161337.

ABSTRACT

Microbiota has emerged as a potential regulator of female reproductive health through immunological, metabolic, and endocrine networks. Growing evidence suggests that the composition and stability of the vaginal, uterine, and gut microbiota are associated with fertility outcomes. Disruptions in reproductive tract homeostasis have been linked to infertility, implantation failure, pregnancy loss, and diminished success in assisted reproductive technologies. Beyond local interactions, maternal gut microbiota may influence systemic immunity and metabolic pathways related to vaginal and endometrial microbiota. While these findings highlight the microbiome-based signatures' potential as predictive and prognostic biomarkers, their clinical applicability remains unconfirmed. Evidence is limited by small cohort sizes, methodological and analytical heterogeneity, and lack of standardization, limiting clinical translation. This narrative review summarizes the current knowledge regarding the microbiome's role in female reproductive health, highlighting its potential impact on pathophysiology, diagnostics, and therapeutic strategies. While this approach allows for a broad conceptual overview, we explicitly note that it is not systematic. As a result, this review is limited by the absence of a standardized search protocol, which may introduce selection bias. Finally, we review advances in microbial engineering and synthetic biology, highlighting engineered living biotherapeutics as promising strategies to improve microbiome-based reproductive medicine.

PMID:42651642 | PMC:PMC13509434 | DOI:10.3390/biology15161337

Biomedicines. 2026 Aug 4;14(8):1755. doi: 10.3390/biomedicines14081755.

ABSTRACT

Background/Objectives: Chronic exposure to endocrine-disrupting chemicals has been increasingly recognized as a potential contributor to cancer progression. Monobutyl phthalate (MBP), a major metabolite of dibutyl phthalate, is widely detected in human biological samples, yet its long-term impact on anaplastic thyroid cancer (ATC) has not been systematically investigated. Methods: CAL-62 cells were continuously exposed to an environmentally relevant concentration of MBP (10 nM) over 3 months to establish a chronic exposure model that mimics long-term environmental exposure. Transcriptomic profiling was integrated with network toxicology to identify key molecular pathways and hub genes, followed by molecular docking and Western blot validation. Results: Chronic MBP exposure significantly enhanced cell viability, proliferation, colony formation, and tumorsphere formation, indicating promotion of malignant phenotypes. Transcriptomic profiling revealed extensive molecular remodeling characterized by activation of inflammation-associated pathways, including cytokine-cytokine receptor interaction, IL-17, TNF, and JAK-STAT signaling, accompanied by suppression of p53- and mTOR-related pathways. Integrated analysis identified 57 overlapping KEGG pathways, with IL6 and CSF2 emerging as central hub genes. Molecular docking demonstrated favorable binding affinities between MBP and representative target proteins, including IL6, TP53, CASP3, BCL2, and PPARG. Western blot analysis further confirmed increased IL6 and BCL2 expression together with decreased TP53, CASP3, and PPARG expression following chronic MBP exposure. Conclusions: Chronic environmentally relevant MBP exposure promotes ATC malignant progression through coordinated inflammation-associated molecular network remodeling accompanied by suppression of apoptosis-related signaling. Integrating network toxicology with transcriptomic profiling provides an effective systems-level strategy for identifying biologically relevant molecular networks underlying chronic environmental toxicant exposure.

PMID:42652139 | PMC:PMC13509629 | DOI:10.3390/biomedicines14081755

Biomedicines. 2026 Aug 1;14(8):1739. doi: 10.3390/biomedicines14081739.

ABSTRACT

Metabolic syndrome (MetS) is a complex metabolic disorder that includes central fat accumulation and insulin resistance, abnormal lipid levels, high blood pressure, and ongoing mild inflammation as its main symptoms. The global rise in metabolic syndrome parallels the increasing prevalence of male infertility, suggesting a potential association between metabolic health and reproductive function. Male fertility suffers from obesity, which represents a major element of metabolic syndrome because it disrupts hormonal balance, raises scrotal temperatures, and causes oxidative damage and HPG axis malfunction. Excess body fat functions as an endocrine system that induces the body to produce pro-inflammatory cytokines, which include tumor necrosis factor-α and interleukin-6, and various other inflammatory substances that result in ongoing body-wide inflammation. The state of inflammation leads to damaged spermatogenesis, which results in lower testosterone production and impaired semen quality that includes changes in sperm concentration, motility, morphology, and DNA integrity. The combination of insulin resistance and metabolic disturbances that occur in MetS leads to oxidative stress and mitochondrial dysfunction, which harms male reproductive abilities in testicular tissue. Recent research shows that adipokines and endocrine disruptors, together with epigenetic modifications, function as mediators that establish the connection between metabolic syndrome and male infertility. The development of targeted therapeutic strategies and lifestyle interventions requires researchers to study how obesity and chronic inflammation interact with each other to create reproductive dysfunction. This review defines the pathophysiological mechanisms that connect metabolic syndrome to male infertility by focusing on how obesity-related inflammation affects male reproductive health.

PMID:42652121 | PMC:PMC13509663 | DOI:10.3390/biomedicines14081739

Life (Basel). 2026 Aug 21;16(8):1379. doi: 10.3390/life16081379.

ABSTRACT

Objectives: The present study evaluated the association between plasma concentrations of selected endocrine-disrupting chemicals (EDCs)-bisphenol A (BPA), methylparaben (MeP), propylparaben (PrP), 4-nonylphenol (4-NP), 4-octylphenol (4-OP), bis(2-ethylhexyl) phthalate (DEHP), and imazalil (IMZ)-and prior coronavirus disease 2019 (COVID-19) status. Methods: Plasma EDC levels were quantified via gas chromatography-mass spectrometry in 262 voluntary blood donors (121 convalescents and 141 controls) at the Regional Centre for Transfusion Medicine in Bialystok, Poland. Results: The cohort exhibited widespread environmental exposure to all selected EDCs (BPA: 1.14 ng/mL, MeP: 1.20 ng/mL, PrP: 1.38 ng/mL, 4-NP: 1.90 ng/mL, 4-OP: 0.57 ng/mL, DEHP: 49.68 ng/mL, IMZ: 20.06 ng/mL). Convalescents had significantly higher concentrations of MeP, PrP, 4-OP, and 4-NP. Logistic regression revealed that MeP, PrP, and 4-NP were significantly associated with prior COVID-19 status, increasing infection odds by 80%, 70%, and 63%, respectively. While 4-OP was strongly associated with prior COVID-19 status (odds ratio > 300 per unit change and 1.79 per 0.1 unit change), the wide confidence interval for the unit change estimate requires cautious interpretation. Conclusions: These findings suggest a strong link between selected paraben and alkylphenol exposure and prior COVID-19 status in blood donors. Additionally, the high IMZ levels highlight the need for urgent evaluation of its safety and environmental prevalence.

PMID:42653067 | PMC:PMC13514347 | DOI:10.3390/life16081379

Int J Mol Sci. 2026 Aug 13;27(16):7218. doi: 10.3390/ijms27167218.

ABSTRACT

Bisphenols (BPs) are widespread environmental endocrine disruptors, but their potential depression-related neurotoxicity has not been systematically assessed. Here, we combined machine learning (ML), network toxicology, molecular docking, and in vivo experiments to screen 26 bisphenols for depression-related neurotoxic risk. We first integrated bisphenol A (BPA)-related targets with depression-related genes to build a chemical-gene-phenotype-disease network and an adverse outcome pathway (AOP) framework. We then used nine ML algorithms to rank the predicted risk of the 26 bisphenols. Molecular docking showed that the predicted high-risk compounds had strong binding affinity for estrogen receptor 1 (ESR1). The AOP analysis further suggested the involvement of the ESR1-cAMP response element-binding protein 1 (CREB1)-glutamate ionotropic receptor N-methyl-D-aspartate type subunit 2B (GRIN2B) pathway. In vivo experiments showed that BPA exposure caused neuronal damage in the cornu ammonis 3 (CA3) region of the rat hippocampus and significantly reduced the messenger RNA (mRNA) expression of the corresponding genes Esr1, Creb1, and Grin2b in hippocampal tissue. Overall, this study screened and prioritized the model-predicted depression-related neurotoxic risk of 26 bisphenols, supports a role for the ESR1-CREB1-GRIN2B pathway in BPA-induced neurotoxicity, and provides mechanistic evidence for bisphenol risk assessment.

PMID:42653223 | PMC:PMC13512944 | DOI:10.3390/ijms27167218

Int J Mol Sci. 2026 Aug 15;27(16):7298. doi: 10.3390/ijms27167298.

ABSTRACT

Rare earth elements (REEs) are increasingly recognized as modulators of male reproductive health. This review presents the first comprehensive and critical analysis of the detrimental and potentially beneficial effects of REEs on male vertebrate reproductive function. In vivo and in vitro studies show that elements, particularly Gadolinium, Lanthanum, and Yttrium, share a toxicological profile characterized by oxidative stress, inflammation, mitochondrial dysfunction, endocrine disruption, and impairment of the blood-testis barrier. These mechanisms converge on both somatic and germ cell populations, ultimately compromising spermatogenesis and hormonal balance. Limited epidemiological data in humans are consistent with experimental findings, indicating inverse associations between seminal REE levels and sperm quality. CeO₂ nanoparticles represent an exception, showing dose-dependent duality: although some murine studies describe toxic effects, a broader and more consistent body of evidence indicates their protective action by restoring testicular homeostasis in diabetic models, in rats exposed to pesticides, pharmacological agents or irradiation, and in in vitro-treated spermatozoa. Preliminary data on Yttrium (YO) and Gadolinium (GdVO₄) nanoparticles similarly point to protective effects under pathological conditions, whereas Neodymium and Samarium show reproductive toxicity, including hormonal disruption and impaired sperm quality. Overall, REEs cannot be considered a homogeneous class: some pose reproductive hazards, others show potential biomedical utility. A systematic, mechanistic research framework is needed to resolve these dualities. It should contextualise reproductive risks in relation to the growing environmental and occupational exposure to REEs, while simultaneously exploring the biomedical potential of those elements that exhibit protective profiles.

PMID:42653303 | PMC:PMC13513206 | DOI:10.3390/ijms27167298

Biomolecules. 2026 Jul 29;16(8):1109. doi: 10.3390/biom16081109.

ABSTRACT

Phthalate esters (PAEs), which are widely used as plasticizers in various products, are recognized as endocrine-disrupting chemicals (EDCs) that can affect female reproductive health. Numerous studies linked PAE exposure to several health hazards, including disruption of folliculogenesis, steroidogenesis, implantation, and pregnancy maintenance, contributing to complications such as miscarriage, preeclampsia, and preterm birth. In response to growing concerns regarding their toxicity, alternative plasticizers (APs) have been introduced, with particular attention given to the commonly used compounds, including di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH), tris(2-ethylhexyl) trimellitate (TOTM), di(2-ethylhexyl) adipate (DEHA), and acetyl tributyl citrate (ATBC). While these alternatives are often presented as safer, recent studies have suggested that these compounds can also disrupt hormonal pathways and fertility regulation mechanisms. Both PAEs and APs have been shown to interact with key nuclear receptor systems, especially with peroxisome proliferator-activated receptors (PPARs) and steroid hormone receptors. These receptors are essential regulators of ovarian function, placental development, and pregnancy maintenance. Disruption of these signaling pathways, particularly in the placenta and fetal membranes, may contribute to altered inflammatory responses, impaired endocrine regulation, and increased risk of adverse pregnancy outcomes. This review provides a state-of-the-art synthesis of the current literature on PAEs and APs, focusing on exposure patterns, associations with female reproductive health and pregnancy outcomes, and the identification of dysregulated biological pathways. This review emphasizes the urgent need to limit plasticizer exposure, especially among women of reproductive age, in order to preserve reproductive health and prevent associated complications.

PMID:42650777 | PMC:PMC13510836 | DOI:10.3390/biom16081109

Children (Basel). 2026 Aug 12;13(8):1068. doi: 10.3390/children13081068.

ABSTRACT

Background: Over the past decades, the global onset of menarche has progressively advanced, driven by complex interactions between metabolic, psychosocial, and environmental factors. Beyond its reproductive significance, menarche represents a critical developmental milestone that coincides with increased vulnerability to mental health difficulties. Contemporary determinants such as childhood obesity, early-life adversity, and exposure to endocrine-disrupting chemicals (EDCs) may accelerate pubertal timing while simultaneously shaping adverse psychological trajectories during adolescence. Objectives: This review aims to provide a translational and clinically oriented synthesis of modern determinants of earlier menarche and their associations with mental health outcomes in girls and adolescents, highlighting implications for early identification, prevention, and integrated clinical care. Methods: We conducted a narrative review mapping a scoping literature search conducted using PubMed/Medline, Scopus, and PsycINFO, focusing on literature from the last decade (2016-2026), with emphasis on systematic reviews, meta-analyses, and longitudinal cohort studies. Evidence was synthesized across biological, psychosocial, and environmental domains. Results: Accumulating evidence indicates that higher childhood adiposity, psychosocial stress, and EDC exposure are consistently associated with advanced pubertal timing. Earlier menarche correlates with an elevated risk of depressive symptoms, anxiety, self-harm, and body image-related distress, although effect sizes vary across populations. Emerging longitudinal data suggest that the peri-menarcheal period represents a critical window for symptom exacerbation. These associations appear to be mediated by biological mechanisms (e.g., hormonal shifts, hypothalamic-pituitary-adrenal (HPA) axis reactivity) and social processes including peer-comparison dynamics and premature sexualization. Conclusions: Earlier menarche acts as a biopsychosocial sentinel event rather than an isolated gynecological milestone. Integrating mental health screening and anticipatory guidance into pediatric and gynecological care is essential for early risk detection. A multidisciplinary, equity-oriented approach is required to address both individual vulnerability and broader environmental determinants.

PMID:42650406 | PMC:PMC13510574 | DOI:10.3390/children13081068

Antioxidants (Basel). 2026 Aug 17;15(8):1021. doi: 10.3390/antiox15081021.

ABSTRACT

Butyl benzyl phthalate (BBP), a widely used endocrine-disrupting chemical, has been associated with reproductive toxicity; however, its long-term effects during aging remain poorly understood. In the present study, we examined the effects of prolonged BBP exposure on the male reproductive system using naturally aged C57BL/6J mice. Mice received BBP at 169 μg/kg/day in drinking water for 10 or 22 months and were analyzed at 24 months of age. No significant differences in body weight, food intake, or water consumption were observed among the experimental groups. Representative gross images showed apparent distension and dark-red discoloration of the seminal vesicles in BBP-exposed aged mice. Compared with Young mice, the BBP-exposed aged groups showed higher expression of IL-1β, IL-6, TNFα, SOD1, and SOD2 and lower CAT expression in the seminal vesicle. H₂DCFDA fluorescence showed a non-significant increasing trend. Because an untreated age-matched Old group was not included in the seminal vesicle analyses, the effects of aging and BBP could not be distinguished. In contrast, the testis showed limited changes in inflammatory cytokine-, antioxidant enzyme-, and steroidogenesis-related gene expression and in H₂DCFDA fluorescence relative to the untreated Old group. Exploratory miRNA sequencing of pooled testicular RNA and comparison with a TM3 Leydig cell dataset identified miR-664-5p as a candidate showing higher relative abundance in both datasets. TargetScan analysis predicted binding sites for miR-664-5p in FOXO1 and FOXO3. In BBP-treated TM3 cells, FOXO3 protein expression was decreased, and FOXO6 expression was increased, whereas FOXO1 showed no consistent dose-dependent change. These molecular findings do not establish direct regulation of FOXO proteins by miR-664-5p or explain the seminal vesicle findings.

PMID:42650285 | PMC:PMC13509467 | DOI:10.3390/antiox15081021

Int J Mol Sci. 2026 Aug 16;27(16):7311. doi: 10.3390/ijms27167311.

ABSTRACT

Bisphenols and phthalates are ubiquitous endocrine-disrupting chemicals with potential effects on reproductive neuroendocrine regulation, particularly during sensitive developmental windows. This review summarizes current evidence on their exposure profile, mechanisms of reproductive disruption, and female- and male-specific reproductive adversities. A structured narrative review was conducted using PubMed/MEDLINE, Scopus, and Web of Science, including experimental, epidemiological, biomonitoring, systematic review, and meta-analytic studies addressing bisphenols, phthalates, fertility, hormonal regulation, gametogenesis, pregnancy outcomes, and reproductive toxicity mechanisms. Bisphenols and phthalates interfere with estrogenic and androgenic signaling, hypothalamic-pituitary-gonadal axis regulation, steroidogenesis, oxidative stress, inflammation, apoptosis, mitochondrial function, and epigenetic regulation. Reported outcomes include impaired ovarian function, altered oocyte development, hormonal imbalance, reduced semen quality, defective spermatogenesis, sperm DNA damage, infertility, and adverse developmental or pregnancy-related effects. However, human evidence remains heterogeneous and limited by observational designs, exposure misclassification, residual confounding, and insufficient mixture assessment. Current evidence supports biological plausibility for bisphenol- and phthalate-related reproductive toxicity, but causal inference remains limited. Prospective studies with repeated biomonitoring, standardized reproductive endpoints, sex- and age-specific analyses, and improved mixture modeling are needed. A precautionary reduction in avoidable exposure appears reasonable, particularly during sensitive reproductive and developmental periods.

PMID:42653315 | PMC:PMC13513600 | DOI:10.3390/ijms27167311

J Xenobiot. 2026 Jul 27;16(4):137. doi: 10.3390/jox16040137.

ABSTRACT

Aquatic animals are increasingly exposed to complex mixtures of emerging environmental toxicants, including microplastics, nanoplastics, per- and polyfluoroalkyl substances (PFAS), and endocrine-disrupting chemicals (EDCs). This raises serious concerns for reproductive health, offspring survival rates, and long-term population stability. This narrative review synthesizes the available peer-reviewed evidence on the reproductive and developmental effects of these contaminant groups in aquatic animals. Growing evidence indicates that these contaminants adversely affect reproductive processes, impair offspring development, and reduce survival and fitness across a wide range of aquatic species. Their effects are mediated through interconnected pathways involving oxidative stress, endocrine disruption, inflammation, mitochondrial dysfunction, and epigenetic alterations, ultimately leading to reproductive and developmental abnormalities. These changes may weaken wild fish populations, reduce aquaculture productivity, and compromise aquatic biodiversity. However, interpretation of the available evidence is constrained by substantial heterogeneity in species, contaminant properties and concentrations, exposure durations, and reproductive endpoints, together with the predominance of laboratory-based single-contaminant studies. This review integrates current knowledge on the reproductive and developmental impacts of emerging contaminants by connecting mechanistic toxicity pathways with population-level and ecosystem consequences. Overall, this review emphasizes that protecting aquatic reproductive health requires an integrated framework linking contaminant monitoring, mechanistic biomarkers, reproductive performance, and ecosystem-level risk assessment.

PMID:42646051 | PMC:PMC13514258 | DOI:10.3390/jox16040137

Toxics. 2026 Jul 29;14(8):673. doi: 10.3390/toxics14080673.

ABSTRACT

Bisphenols, phthalates, and other plastic-associated compounds are endocrine-disrupting chemicals (EDCs), common environmental contaminants that can disrupt hormonal homeostasis. Human exposure to such chemicals occurs mainly through food packaging, consumer goods, medical devices, and the environment, starting right from early development stages up to adulthood. These chemicals might cause damage to male reproductive systems as a result of being anti-androgens and estrogenic chemicals. However, the proper development of the male reproductive system requires well-regulated hormonal signaling pathways; hence, exposure to such compounds during the developmental stages poses a great risk. Environmental exposure to plastics during fetal development may influence the development of the testes, reduce the function of the Leydig cells, disrupt steroidogenesis, and produce epigenetic modifications, as documented through studies. This has been shown to increase the risk of developing reproductive disorders and reduce the production of testosterone. Therefore, one of the pathophysiological links between endocrine disruptor exposure and ED might be testosterone deficiency. Apart from disrupting testosterone production, the plastic-sourced EDCs could influence various physiological processes associated with erectile performance, such as those related to vasculature, inflammation, metabolism, and endocrinology. In this review, a comprehensive overview of the scientific data on the effect of plastic-based EDCs on testosterone regulation and male reproductive health has been provided. The role of developmental programming, endocrine disruption, oxidative stress, epigenetics, and vascular dysfunction has been explored in detail. Moreover, the possible involvement of micro- and nanoplastics has also been reviewed. From the data that is currently available, there seems to be a physiologically plausible association between plastic-based contaminants, testosterone dysregulation, and adverse reproductive outcomes.

PMID:42646955 | PMC:PMC13517508 | DOI:10.3390/toxics14080673

Toxics. 2026 Aug 21;14(8):734. doi: 10.3390/toxics14080734.

ABSTRACT

Cyanobacterial harmful algal blooms have increased globally, likely in part due to climate change and anthropogenic eutrophication, elevating exposure of humans and other terrestrial and aquatic animals to cyanotoxins through drinking water, food chains, and recreational activities. Microcystin-LR (MC-LR), the most prevalent microcystin congener, is well known for its hepatotoxicity, yet accumulating evidence indicates that it also exerts reproductive and developmental toxicity in mammals. This review summarizes recent experimental and epidemiological studies indicating that MC-LR disrupts reproductive function through direct cellular injury to germ and somatic cells, dysregulation of gonadal steroidogenesis, and impairment of the hypothalamic-pituitary-gonadal (HPG) axis. In males, MC-LR disrupts spermatogenesis and sperm quality, while in females it impairs oocyte competence, uterine receptivity, and placental function, leading to adverse pregnancy outcomes. Importantly, exposure during critical developmental windows can influence developmental trajectories and contribute to long-term, multi-organ dysfunction in offspring via endocrine imbalance and epigenetic reprogramming. Mechanistically, MC-LR toxicity involves convergent oxidative stress, mitochondrial dysfunction, inflammatory signaling, DNA damage, and chromatin remodeling. Collectively, these findings indicate that reproductive and developmental toxicity should be considered in assessments of the health risks associated with MC-LR and support the incorporation of reproductive endpoints into human health and ecological risk assessment frameworks.

PMID:42647017 | PMC:PMC13517335 | DOI:10.3390/toxics14080734

J Xenobiot. 2026 Jul 27;16(4):137. doi: 10.3390/jox16040137.

ABSTRACT

Aquatic animals are increasingly exposed to complex mixtures of emerging environmental toxicants, including microplastics, nanoplastics, per- and polyfluoroalkyl substances (PFAS), and endocrine-disrupting chemicals (EDCs). This raises serious concerns for reproductive health, offspring survival rates, and long-term population stability. This narrative review synthesizes the available peer-reviewed evidence on the reproductive and developmental effects of these contaminant groups in aquatic animals. Growing evidence indicates that these contaminants adversely affect reproductive processes, impair offspring development, and reduce survival and fitness across a wide range of aquatic species. Their effects are mediated through interconnected pathways involving oxidative stress, endocrine disruption, inflammation, mitochondrial dysfunction, and epigenetic alterations, ultimately leading to reproductive and developmental abnormalities. These changes may weaken wild fish populations, reduce aquaculture productivity, and compromise aquatic biodiversity. However, interpretation of the available evidence is constrained by substantial heterogeneity in species, contaminant properties and concentrations, exposure durations, and reproductive endpoints, together with the predominance of laboratory-based single-contaminant studies. This review integrates current knowledge on the reproductive and developmental impacts of emerging contaminants by connecting mechanistic toxicity pathways with population-level and ecosystem consequences. Overall, this review emphasizes that protecting aquatic reproductive health requires an integrated framework linking contaminant monitoring, mechanistic biomarkers, reproductive performance, and ecosystem-level risk assessment.

PMID:42646051 | PMC:PMC13514258 | DOI:10.3390/jox16040137

J Environ Manage. 2026 Aug 26;416:130775. doi: 10.1016/j.jenvman.2026.130775. Online ahead of print.

ABSTRACT

Bisphenol A (BPA) as a typical endocrine-disrupting chemical has attracted extensive attention due to its persistent pollution and high biotoxicity. Traditional water treatment technologies suffer from low efficiency, high cost and secondary pollution in removing trace BPA. Herein, MIL-101(Fe) was hydrophobically modified with alkyltrimethylammonium bromides (TTAB, CTAB, OTAB) to construct a bifunctional flotation collector, which integrates high adsorption capacity and excellent foam stabilization. The structure-interfacial property-performance relationship was systematically investigated. Results demonstrated that 6 mmol/L OTAB-modified MIL-101(Fe) exhibited optimized amphiphilicity, foamability and adsorption performance, with a maximum BPA adsorption capacity of 185.03 mg/g. Under optimal foam flotation conditions (dosage = 300 mg/L, pH = 4, gas flow = 500 mL/min), the BPA removal efficiency and enrichment ratio reached 93.67% and 13.11, respectively. The material displayed superior selectivity and satisfactory reusability in simulated wastewater. This work provides a promising strategy for highly efficient separation and removal of trace hydrophobic organic pollutants via MOF-based foam flotation.

PMID:42648220 | DOI:10.1016/j.jenvman.2026.130775

Environ Toxicol Pharmacol. 2026 Aug 26;127:105148. doi: 10.1016/j.etap.2026.105148. Online ahead of print.

ABSTRACT

Bisphenol A (BPA) is a pervasive endocrine-disrupting chemical with documented toxic effects in living organisms. This study evaluated the protective potential of vanillic acid (VA) against BPA-induced toxicity in Drosophila melanogaster. BPA exposure elevated lipid peroxidation (MDA), reduced antioxidant defenses (SOD and CAT activities and GSH content), increased DNA damage (Comet assay), lowered acetylcholinesterase levels, and impaired developmental parameters (pupation, climbing, crawling, lifespan, and food intake). BPA also upregulated SOD, CAT, gclc, hsp70, CncC, and Keap1 mRNA expression, indicating activation of the cellular stress response. VA co-treatment dose-dependently mitigated these effects, restoring redox balance, reducing DNA strand breaks at the highest VA dose, and rescuing developmental endpoints. These findings suggest that VA is an effective natural protective agent against BPA toxicity in vivo, an effect accompanied by modulation of CncC/Keap1 pathway gene expression.

PMID:42648388 | DOI:10.1016/j.etap.2026.105148

J Environ Sci Health A Tox Hazard Subst Environ Eng. 2026 Aug 26:1-20. doi: 10.1080/10934529.2026.2722474. Online ahead of print.

ABSTRACT

Microplastics, as carriers of environmental pollutants, may influence their biological effects through adsorption. The adsorption mechanism of polyethylene terephthalate microplastics (PET MPs) on the endocrine disrupting compound nonylphenol ethoxylate (NPE) is studied. Furthermore, the effect of the PET MPs-NPE complex on the structure and function of the carrier protein bovine serum albumin (BSA) is further explored. The adsorption process of PET MPs on NPE conforms to the pseudo-second-order kinetic model (R² = 0.9985) and Freundlich model (R² = 0.9241), and belongs to a spontaneous, endothermic, and entropy-increasing process. PET MPs function as effective NPE carriers, achieving a desorption rate of 59.29% in acidic buffer solution (pH 1.2), suggesting that ingestion may enhance NPE release risk in vivo. Multispectral analysis showed that free PET MPs and NPE were bound to Site II of BSA through hydrogen bonding and van der Waals forces, altering BSA's secondary structure. When PET MPs and NPE coexist, they exhibit a combined effect, manifested by significantly enhanced binding affinity with BSA (K_b from 5.39 × 10⁴ M^-1 to 2.71 × 10⁵ M^-1) and higher disturbance to BSA conformation than a single component. The PET MPs-NPE complex triggers pronounced conformational changes in BSA, suppresses esterase-like activity, and alters thiol content.

PMID:42644688 | DOI:10.1080/10934529.2026.2722474

Toxics. 2026 Jul 29;14(8):673. doi: 10.3390/toxics14080673.

ABSTRACT

Bisphenols, phthalates, and other plastic-associated compounds are endocrine-disrupting chemicals (EDCs), common environmental contaminants that can disrupt hormonal homeostasis. Human exposure to such chemicals occurs mainly through food packaging, consumer goods, medical devices, and the environment, starting right from early development stages up to adulthood. These chemicals might cause damage to male reproductive systems as a result of being anti-androgens and estrogenic chemicals. However, the proper development of the male reproductive system requires well-regulated hormonal signaling pathways; hence, exposure to such compounds during the developmental stages poses a great risk. Environmental exposure to plastics during fetal development may influence the development of the testes, reduce the function of the Leydig cells, disrupt steroidogenesis, and produce epigenetic modifications, as documented through studies. This has been shown to increase the risk of developing reproductive disorders and reduce the production of testosterone. Therefore, one of the pathophysiological links between endocrine disruptor exposure and ED might be testosterone deficiency. Apart from disrupting testosterone production, the plastic-sourced EDCs could influence various physiological processes associated with erectile performance, such as those related to vasculature, inflammation, metabolism, and endocrinology. In this review, a comprehensive overview of the scientific data on the effect of plastic-based EDCs on testosterone regulation and male reproductive health has been provided. The role of developmental programming, endocrine disruption, oxidative stress, epigenetics, and vascular dysfunction has been explored in detail. Moreover, the possible involvement of micro- and nanoplastics has also been reviewed. From the data that is currently available, there seems to be a physiologically plausible association between plastic-based contaminants, testosterone dysregulation, and adverse reproductive outcomes.

PMID:42646955 | PMC:PMC13517508 | DOI:10.3390/toxics14080673

J Endocrinol Invest. 2026 Aug 26. doi: 10.1007/s40618-026-03030-y. Online ahead of print.

ABSTRACT

BACKGROUND AND AIM: obesity is a major global health concern tightly linked to insulin resistance and type 2 diabetes. Environmental exposure to endocrine-disrupting chemicals (EDs), including bisphenols (BPs) and perfluoroalkyl substances (PFs), has been implicated in metabolic dysfunction, yet the impact of chronic low-dose co-exposure on human adipocyte development and insulin responsiveness remains poorly defined. Here, we evaluated bisphenol S (BPS) and perfluorooctane sulfonate (PFOS), alone or combined, in human adipose-derived stem cells undergoing adipogenic differentiation.

METHODS: Cells were chronically exposed to environmentally relevant low doses of bisphenol S (BPS) and perfluorooctane sulfonate (PFOS), alone or in combination, throughout adipogenic differentiation.

RESULTS: Lipid droplet accumulation was unchanged across conditions, indicating preserved terminal differentiation. In contrast, BPS and PFOS altered the timing and magnitude of key adipogenic transcriptional programs (CEBPA, PPARγ) and the mature adipocyte marker FABP4. PFOS and BPS+PFOS selectively increased IL1β expression in mature adipocytes, suggesting a limited pro-inflammatory shift. Functionally, all ED-treated groups showed reduced insulin-stimulated glucose uptake, associated with impaired GLUT4 translocation to the plasma membrane despite unchanged total GLUT4 levels. Notably, combined exposure produced the strongest defects in insulin signalling, reducing PI3K pathway activation and decreasing total AKT and ERK1/2 protein levels. In contrast, individually administered BPS and PFOS impaired glucose uptake without detectable PI3K alterations, suggesting the involvement of additional mechanisms.

CONCLUSION: Overall, chronic low-dose exposure to BPS and PFOS disrupts adipocyte transcriptional and signalling networks, inducing features consistent with impaired insulin responsiveness and underscoring the importance of considering ED mixtures in metabolic risk assessment.

PMID:42645757 | DOI:10.1007/s40618-026-03030-y

Curr Nutr Rep. 2026 Aug 26;15(1):70. doi: 10.1007/s13668-026-00790-0.

ABSTRACT

PURPOSE OF REVIEW: This position paper by the Italian Association of Dietetics and Clinical Nutrition (ADI) evaluates the impact of ultra-processed foods (UPFs) on metabolic health and chronic disease risk, with particular attention to the biological and behavioural mechanisms involved.

RECENT FINDINGS: High UPFs consumption has been associated with obesity, insulin resistance, cardiovascular disease, metabolic dysfunction-associated steatotic liver disease (MASLD), cancer, neuroinflammation, and immune dysregulation. Proposed mechanisms include gut microbiota alterations, increased intestinal permeability, mitochondrial dysfunction, oxidative stress, impaired metabolic flexibility, and chronic low-grade inflammation. The hyperpalatable nature of UPFs may also impair appetite regulation and promote overconsumption, especially among children and adolescents. Additional concerns involve food additives, processing-derived contaminants, and endocrine disruptors from packaging materials. Current evidence identifies UPFs as a major modifiable risk factor for non-communicable chronic diseases. Reducing UPFs exposure should therefore represent a public health priority, supported by preventive nutritional strategies, improved food classification systems, and targeted educational and regulatory interventions.

PMID:42645708 | PMC:PMC13518480 | DOI:10.1007/s13668-026-00790-0

Endocr J. 2026 Aug 26. doi: 10.1507/endocrj.EJ26-0175. Online ahead of print.

ABSTRACT

Mutations in the CACNA1H and PPP2R5D genes have been associated with functional abnormalities affecting both the endocrine and nervous systems. The CACNA1H gene encodes the T-type calcium channel CaV3.2, and pathogenic variants may alter channel activation and inactivation, resulting in increased intracellular calcium influx. Elevated intracellular calcium in adrenal zona glomerulosa cells acts as a key signal for aldosterone biosynthesis, thereby promoting excessive aldosterone secretion and contributing to the development of hypertension. The PPP2R5D gene encodes a regulatory subunit of protein phosphatase 2A (PP2A). Mutations in this gene may disrupt the regulatory function of PP2A, impairing the dephosphorylation of key neuroproteins and consequently affecting neural signal transduction and brain function. Cases of early-onset hypertension accompanied by intellectual disability associated with concurrent CACNA1H and PPP2R5D mutations remain rare. We report the case of an 18-year-old female presenting with early-onset hypertension and intellectual disability. Hypertension was first diagnosed at the age of 10 years and was accompanied by recurrent dizziness and headache. Physical examination revealed central obesity and signs of hyperandrogenism. Laboratory evaluation demonstrated elevated aldosterone levels with suppressed plasma renin activity, suggesting primary aldosteronism. Genetic analysis identified heterozygous variants in CACNA1H (c.6866C>T) and PPP2R5D (c.985A>G). Based on the clinical features and genetic findings, the patient was diagnosed with familial hyperaldosteronism type IV complicated by intellectual disability. This case highlights the importance of considering genetic forms of primary aldosteronism in young patients with early-onset hypertension and atypical clinical manifestations. Genetic testing may facilitate accurate diagnosis and guide individualized management.

PMID:42649046 | DOI:10.1507/endocrj.EJ26-0175

J Xenobiot. 2026 Jul 27;16(4):137. doi: 10.3390/jox16040137.

ABSTRACT

Aquatic animals are increasingly exposed to complex mixtures of emerging environmental toxicants, including microplastics, nanoplastics, per- and polyfluoroalkyl substances (PFAS), and endocrine-disrupting chemicals (EDCs). This raises serious concerns for reproductive health, offspring survival rates, and long-term population stability. This narrative review synthesizes the available peer-reviewed evidence on the reproductive and developmental effects of these contaminant groups in aquatic animals. Growing evidence indicates that these contaminants adversely affect reproductive processes, impair offspring development, and reduce survival and fitness across a wide range of aquatic species. Their effects are mediated through interconnected pathways involving oxidative stress, endocrine disruption, inflammation, mitochondrial dysfunction, and epigenetic alterations, ultimately leading to reproductive and developmental abnormalities. These changes may weaken wild fish populations, reduce aquaculture productivity, and compromise aquatic biodiversity. However, interpretation of the available evidence is constrained by substantial heterogeneity in species, contaminant properties and concentrations, exposure durations, and reproductive endpoints, together with the predominance of laboratory-based single-contaminant studies. This review integrates current knowledge on the reproductive and developmental impacts of emerging contaminants by connecting mechanistic toxicity pathways with population-level and ecosystem consequences. Overall, this review emphasizes that protecting aquatic reproductive health requires an integrated framework linking contaminant monitoring, mechanistic biomarkers, reproductive performance, and ecosystem-level risk assessment.

PMID:42646051 | PMC:PMC13514258 | DOI:10.3390/jox16040137

Anal Chim Acta. 2026 Oct 22;1420:345961. doi: 10.1016/j.aca.2026.345961. Epub 2026 Jul 10.

ABSTRACT

Lipidomics is a powerful approach for investigating lipid alterations in complex biological systems. However, conventional liquid chromatography coupled to mass spectrometry (LC-MS) may be limited in non-targeted studies due to the high structural diversity and wide concentration range of lipid species. In this work, an optimized comprehensive two-dimensional liquid chromatography coupled to high-resolution mass spectrometry (LC×LC-HRMS) workflow was developed for non-targeted lipidomics. The method combines reversed-phase (RP) separation in the first chromatographic dimension with hydrophilic interaction liquid chromatography (HILIC) separation in the second dimension (RP×HILIC) and incorporates active solvent modulation (ASM) as an interface between the two chromatographic dimensions to improve analytical sensitivity and solvent compatibility across both dimensions. This approach improves sensitivity, solvent compatibility and lipidome coverage compared to conventional LC-MS workflows. The proposed workflow was applied to investigate lipidomic alterations in zebrafish (Danio rerio) eleutheroembryos exposed to the endocrine-disrupting chemical bisphenol A (BPA), using 17β-estradiol (E2) as an estrogenic control. The LC×LC-HRMS approach enabled enhanced lipidome coverage, resulting in the detection of 567 lipid features, of which 134 showed significant alterations associated with endocrine-disruptor exposure. Comparative analysis revealed lipidomic changes consistent with estrogenic responses for both BPA and E2 treatments, while additional lipid alterations suggested potential obesogenic effects under E2 exposure. In summary, the proposed LC×LC-HRMS workflow with ASM provides enhanced separation performance. The obtained results demonstrate the potential of comprehensive multidimensional chromatography combined with multivariate analysis tools for in-depth lipidomics studies in complex biological samples.

PMID:42648837 | DOI:10.1016/j.aca.2026.345961

Endocrinology. 2026 Aug 26:bqag097. doi: 10.1210/endocr/bqag097. Online ahead of print.

ABSTRACT

Tributyltin (TBT) is an environmental obesogen and endocrine-disrupting chemical that promotes adipogenesis and transgenerational metabolic dysfunction in mice. Although developmental TBT exposure has been linked to male-biased adiposity, insulin dysregulation, and hepatic pathology, its effects on the immune system remain unclear. We investigated whether maternal TBT exposure is associated with persistent immune dysregulation in F1 and F3 offspring. Peripheral blood immunophenotyping data generated by the German Mouse Clinic were reanalyzed in F1 offspring of control- and TBT-exposed dams. Maternal TBT exposure was associated with increased B-cell representation, reduced T-cell representation, an altered B-cell-to-T-cell balance, a reduced CD4/CD8 ratio, and decreased NK-cell frequencies. We then analyzed splenic immune-marker expression and circulating inflammatory cytokines in an independent transgenerational cohort. In F1 males, TBT exposure was associated with reduced expression of T-cell- and myeloid-associated markers and increased expression of inflammatory cytokines. Similar changes were observed in unexposed F3 male descendants of the TBT lineage, whereas F3 females showed no significant changes in the immune markers examined. Plasma TNF and IL-6 were increased in F1 and F3 males but not females. These findings identify the immune system as a potential target of developmental obesogen exposure and support a persistent, male-biased immune phenotype characterized by altered splenic immune-marker expression and elevated inflammatory cytokines across generations.

PMID:42644284 | DOI:10.1210/endocr/bqag097

Front Immunol. 2026 Aug 11;17:1874855. doi: 10.3389/fimmu.2026.1874855. eCollection 2026.

ABSTRACT

Ferroptosis is a regulated form of cell death driven by iron-dependent lipid peroxidation, characterized by disruption of iron homeostasis, imbalance in the antioxidant system, and accumulation of lipid peroxides. Its core execution machinery is highly conserved across tissues, whereas disease-specific upstream nodes dictate pathway activation and progression in different pathological contexts. In autoimmune hepatitis (AIH), ferroptosis is governed by a "bidirectional imbalance" between enhanced pro-death signals and compromised anti-death protective mechanisms, further modulated by endocrine and metabolic factors. This imbalance collectively lowers the ferroptosis threshold in hepatocytes, amplifying their susceptibility to ferroptotic cell death. Although hepatocyte ferroptosis has been observed in experimental cholestasis models, these models do not directly represent the pathological process of primary biliary cholangitis (PBC). In PBC patients, recent studies have identified ferroptosis signals in monocyte-derived macrophages, but ferroptosis in biliary epithelial cells remains unconfirmed. In primary sclerosing cholangitis (PSC), despite elevated oxidative stress markers, the absence of core ferroptosis executioner molecules precludes any definitive link to ferroptosis. This review comprehensively summarizes the ferroptosis regulatory network and its disease-specific manifestations across autoimmune liver diseases, with a focus on AIH-specific nodes as potential precision intervention targets. We also propose a phase-based therapeutic framework and discuss safety considerations, as well as key challenges for clinical translation.

PMID:42643958 | PMC:PMC13504418 | DOI:10.3389/fimmu.2026.1874855

J Environ Sci Health A Tox Hazard Subst Environ Eng. 2026 Aug 26:1-20. doi: 10.1080/10934529.2026.2722474. Online ahead of print.

ABSTRACT

Microplastics, as carriers of environmental pollutants, may influence their biological effects through adsorption. The adsorption mechanism of polyethylene terephthalate microplastics (PET MPs) on the endocrine disrupting compound nonylphenol ethoxylate (NPE) is studied. Furthermore, the effect of the PET MPs-NPE complex on the structure and function of the carrier protein bovine serum albumin (BSA) is further explored. The adsorption process of PET MPs on NPE conforms to the pseudo-second-order kinetic model (R² = 0.9985) and Freundlich model (R² = 0.9241), and belongs to a spontaneous, endothermic, and entropy-increasing process. PET MPs function as effective NPE carriers, achieving a desorption rate of 59.29% in acidic buffer solution (pH 1.2), suggesting that ingestion may enhance NPE release risk in vivo. Multispectral analysis showed that free PET MPs and NPE were bound to Site II of BSA through hydrogen bonding and van der Waals forces, altering BSA's secondary structure. When PET MPs and NPE coexist, they exhibit a combined effect, manifested by significantly enhanced binding affinity with BSA (K_b from 5.39 × 10⁴ M^-1 to 2.71 × 10⁵ M^-1) and higher disturbance to BSA conformation than a single component. The PET MPs-NPE complex triggers pronounced conformational changes in BSA, suppresses esterase-like activity, and alters thiol content.

PMID:42644688 | DOI:10.1080/10934529.2026.2722474

Front Child Adolesc Psychiatry. 2026 Aug 11;5:1865057. doi: 10.3389/frcha.2026.1865057. eCollection 2026.

ABSTRACT

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterised by restricted and repetitive behaviours (ICD-11) and severe and persistent difficulties in social interaction and communication. A marked male predominance has consistently been reported, with ASD being three times more common among boys than girls, although the biological mechanisms underlying this sex difference remain unknown. Physical and chemical stressors occurring during critical windows of development may alter foetal and infant physiology and interfere with neurodevelopmental trajectories. Among these stressors, endocrine-disrupting chemicals (EDCs), including phthalates, have been proposed as potential environmental contributors to neurodevelopmental vulnerability. In this systematic review, we examined whether early-life exposure to phthalates may be associated with sex-specific vulnerability to ASD and autistic traits.

METHODS: The systematic review was conducted in accordance with the PRISMA guidelines and followed a PECO framework. The target population included human children of both sexes, ranging from early childhood to adolescence. Exposures of interest included prenatal and/or early-life exposure to phthalates, assessed through biological matrices during prenatal and/or postnatal periods. Eligible outcomes included ASD and autistic-like traits assessed using validated diagnostic or screening tools. The review was registered in PROSPERO (CRD420261438630).

RESULTS: A total of 18 studies were included. Phthalates exposure was assessed across a broad developmental window, ranging from the preconception period to 8 years of age. Urinary biomarkers represented the primary method for assessing chemical exposure, while a smaller proportion of studies also relied on blood samples. Sample size ranged from 77 to 3,220, and the age at assessment of autistic traits or ASD-related outcomes ranged from 18 months to 15 years. The Social Responsiveness Scale (SRS) was the most frequently used instrument for assessing autistic traits, followed by the Autism Diagnostic Observation Schedule (ADOS).

CONCLUSION: Prenatal exposure to phthalates, especially during early and mid-gestation, appears to be associated with subtle increases in autistic traits, with some evidence suggesting greater susceptibility among boys, particularly in relation to MBP, MEP, and DEHP-related metabolites. However, evidence remains limited and heterogeneous, and current findings require further confirmation.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/home, PROSPERO CRD420261438630.

PMID:42643251 | PMC:PMC13503302 | DOI:10.3389/frcha.2026.1865057

Vet Med (Praha). 2026 Jul 29;71(7):280-294. doi: 10.17221/95/2025-VETMED. eCollection 2026 Jul.

ABSTRACT

Although microplastic toxicity in fish has been extensively studied, the role of polymer additives remains insufficiently understood. This study investigated the combined effects of polystyrene (PS) microplastics and the brominated flame retardant hexabromocyclododecane (HBCD) on the health of rainbow trout (Oncorhynchus mykiss) following six weeks of dietary exposure. Fish were exposed to PS particles with varying HBCD content (0.0 mg/g - PS-HBCD_free, 0.2 mg/g - PS-HBCD_low, 1.0 mg/g - PS-HBCD_high) or to HBCD alone (HBCD_only). The combination of PS and HBCD induced the most pronounced biological responses at molecular, biochemical and histological levels. In the liver, oxidative stress and upregulation of pro-inflammatory cytokines (il8, il2), together with increased catalase expression, were observed in PS- and/or PS-HBCD-exposed groups, indicating an imbalance in antioxidant defence. Histopathology confirmed liver dystrophy and renal lesions, while elevated vitellogenin expression suggested endocrine disruption. Although HBCD accumulation was confirmed only in the HBCD_only group, the polymer-bound form caused comparable physiological alterations, supporting its contribution to combined toxicity. Overall, the study demonstrates that PS microparticles can act as vectors enhancing the bioactivity of embedded additives such as HBCD, resulting in complex multi-organ effects and emphasising the importance of assessing additive-polymer interactions when evaluating the environmental risks of microplastics.

PMID:42639346 | PMC:PMC13501264 | DOI:10.17221/95/2025-VETMED

Front Immunol. 2026 Aug 10;17:1874215. doi: 10.3389/fimmu.2026.1874215. eCollection 2026.

ABSTRACT

Ankylosing spondylitis (AS) is increasingly recognized as a systemic inflammatory disease accompanied by substantial glucolipid metabolic disturbances and an elevated risk of diabetes. Beyond articular inflammation, persistent immune activation reshapes metabolic homeostasis through interconnected mechanisms involving chronic cytokine signaling, immune-cell metabolic reprogramming, gut microbiota dysbiosis and endocrine disruption. Key mediators, including TNF-α, IL-6 and IL-17, promote insulin resistance, lipid abnormalities and endothelial dysfunction, while Th17/Treg imbalance, neutrophil activation and microbial metabolite alterations further amplify metabolic injury. These pathogenic interactions establish a self-reinforcing cycle in which inflammation and metabolic dysfunction mutually exacerbate one another. Emerging evidence also indicates that anti-inflammatory therapies, nutritional strategies and metabolic modulators may provide dual benefits by controlling disease activity while improving metabolic outcomes. This review summarizes the mechanistic links between AS and glucolipid dysregulation and highlights integrated therapeutic strategies, including pharmacological interventions, nutritional approaches, and natural products/traditional Chinese medicine, for reducing diabetes risk and improving long-term prognosis in AS.

PMID:42638887 | PMC:PMC13501146 | DOI:10.3389/fimmu.2026.1874215

Front Immunol. 2026 Aug 10;17:1923197. doi: 10.3389/fimmu.2026.1923197. eCollection 2026.

ABSTRACT

BACKGROUND: Adrenocorticotropic hormone (ACTH) is a first-line neuroendocrine-immunomodulatory therapy for infantile epileptic spasms syndrome (IESS), but noninvasive electrophysiological markers that objectively reflect treatment-related network changes remain limited. We investigated whether scalp putative ripple propagation network metrics provide markers of adrenocorticotropic hormone-related network response and early relapse risk.

METHODS: In this retrospective multicenter study, children receiving first-time ACTH therapy were included if paired pre- and post-treatment scalp electroencephalography (EEG) recordings and at least 6 months of follow-up were available. Five-minute artifact-free interictal slow-wave-sleep segments were analyzed. Putative ripple propagation networks were constructed using a time-delay-based method. The primary metrics were post-treatment total network connection strength (total NCS) and its reduction ratio, with ripple count and ripple-count reduction ratio used as rate-based comparators.

RESULTS: Sixty-one children were included; 27 achieved acute spasm freedom, and seven of these relapsed within 6 months. Baseline ripple count and network metrics did not distinguish subsequent responders from nonresponders. After adrenocorticotropic hormone therapy, acute responders showed marked suppression of putative ripple propagation network metrics, whereas nonresponders showed reduction in ripple count without comparable reductions in network metrics. Post-treatment total network connection strength and its reduction ratio differentiated acute responders from nonresponders, with areas under the curve (AUC) of 0.902 and 0.899, respectively. In exploratory analyses among acute responders, greater total network connection strength reduction was associated with sustained 6-month spasm freedom, although relapse-related estimates were limited by the small number of events.

CONCLUSION: Scalp putative ripple propagation networks provide a noninvasive electrophysiological readout of ACTH-related network modulation in infantile epileptic spasms syndrome. In contrast to ripple count alone, network connection strength captured whether treatment was accompanied by disruption of propagating high-frequency activity. These findings suggest that total NCS and its reduction ratio may serve as candidate markers of adrenocorticotropic hormone-related neuroendocrine-immunomodulatory therapy response, while their relevance to relapse risk requires prospective validation.

PMID:42638699 | PMC:PMC13500334 | DOI:10.3389/fimmu.2026.1923197

Nanoscale Adv. 2026 Jul 27. doi: 10.1039/d6na00257a. Online ahead of print.

ABSTRACT

Phthalic acid esters (PAEs) are high-volume manufacturing organic materials used in plasticisers to increase the elasticity of the core polymer. They are reported to spread into the surroundings from plastic products and are now a global environmental contaminant. Several environmental sources, particularly water, have been examined for phthalate contaminant levels. These substances are discharged directly into the environment and cannot be chemically bound. The presence of PAEs in different ecological environments is a major concern since they are endocrine disruptors and can interact with hormones, which can lead to problems with development and reproduction. Earlier studies have explored the occurrence, fate, and concentration of phthalates. This review discusses how different oxidative techniques employed for modifying carbon nanotubes (CNTs) can improve their ability to remove PAEs by changing their surface chemistry. Several oxidation approaches introduce oxygenated functional groups on the CNT surface, which increase their specific surface area, making them suitable for adsorbing contaminants like phthalate esters. The adsorption capacity was found to be controlled by the nanotubes' specific surface areas, which varied with their outer diameters. Because of the π-π interaction between the graphitic surface of the nanotubes and the benzene ring of the phthalates, as well as hydrogen bonds, charge-assisted hydrogen bonding, van der Waals forces, and electrostatic interactions between PAEs and CNTs, the adsorption capacity was much higher than that of other materials. PAEs' toxicological and environmental effects have drawn global attention. The present article reviews the use of oxidised CNTs in advanced carbon materials for removing PAEs from polluted and hazardous environments.

PMID:42639539 | PMC:PMC13502127 | DOI:10.1039/d6na00257a

Vet Med (Praha). 2026 Jul 29;71(7):280-294. doi: 10.17221/95/2025-VETMED. eCollection 2026 Jul.

ABSTRACT

Although microplastic toxicity in fish has been extensively studied, the role of polymer additives remains insufficiently understood. This study investigated the combined effects of polystyrene (PS) microplastics and the brominated flame retardant hexabromocyclododecane (HBCD) on the health of rainbow trout (Oncorhynchus mykiss) following six weeks of dietary exposure. Fish were exposed to PS particles with varying HBCD content (0.0 mg/g - PS-HBCD_free, 0.2 mg/g - PS-HBCD_low, 1.0 mg/g - PS-HBCD_high) or to HBCD alone (HBCD_only). The combination of PS and HBCD induced the most pronounced biological responses at molecular, biochemical and histological levels. In the liver, oxidative stress and upregulation of pro-inflammatory cytokines (il8, il2), together with increased catalase expression, were observed in PS- and/or PS-HBCD-exposed groups, indicating an imbalance in antioxidant defence. Histopathology confirmed liver dystrophy and renal lesions, while elevated vitellogenin expression suggested endocrine disruption. Although HBCD accumulation was confirmed only in the HBCD_only group, the polymer-bound form caused comparable physiological alterations, supporting its contribution to combined toxicity. Overall, the study demonstrates that PS microparticles can act as vectors enhancing the bioactivity of embedded additives such as HBCD, resulting in complex multi-organ effects and emphasising the importance of assessing additive-polymer interactions when evaluating the environmental risks of microplastics.

PMID:42639346 | PMC:PMC13501264 | DOI:10.17221/95/2025-VETMED

Toxicol Appl Pharmacol. 2026 Aug 25:118017. doi: 10.1016/j.taap.2026.118017. Online ahead of print.

ABSTRACT

Allergic rhinitis (AR) is a prevalent inflammatory disorder of the upper airways, and exposure to environmental endocrine-disrupting chemicals such as bisphenol A (BPA) and bisphenol F (BPF) has been implicated in its pathogenesis, yet the underlying molecular mechanisms remain poorly understood. We integrated network toxicology, bioinformatics, and machine learning approaches to identify key target genes linking BPA/BPF exposure to AR, followed by molecular docking, molecular dynamics simulations, and surface plasmon resonance (SPR) to evaluate binding affinities. In vitro experiments using human nasal epithelial cells (HNEpC) were conducted to validate the effects of BPA/BPF on cell viability, apoptosis, inflammatory cytokines, senescence-associated secretory phenotype (SASP), and the NF-κB signaling pathway, with further functional assessment via MMP9 overexpression. Four common genes (MAPT, MMP9, CHRM3, ESR2) were identified for BPA and three (MMP9, CHRM3, ESR2) for BPF. SPR confirmed direct binding of both bisphenols to MMP9 with KD values of 3.46 μM (BPA) and 9.47 μM (BPF). BPA/BPF treatment inhibited cell viability, suppressed MMP9, promoted apoptosis, upregulated IL-4, IL-6, IL-8, IL-13, CCL2, TNF-α, and IL-1β, downregulated MMP1, and suppressed the NF-κB pathway. MMP9 overexpression reversed these effects. Our findings demonstrate that BPA and BPF promote AR pathogenesis through MMP9 suppression, SASP activation, and NF-κB inhibition, identifying MMP9 as a potential therapeutic target for pollutant-exacerbated AR.

PMID:42641697 | DOI:10.1016/j.taap.2026.118017

Food Chem Toxicol. 2026 Aug 26;218:116354. doi: 10.1016/j.fct.2026.116354. Online ahead of print.

ABSTRACT

BACKGROUND: Parabens, alkyl esters of p-hydroxybenzoic acid used as antimicrobial preservatives in food, pharmaceuticals, and cosmetics, are endocrine-disrupting chemicals (EDCs). Stage-specific data on paraben transfer through breast milk and exposure estimates for Taiwanese infants are lacking.

METHODS: We quantified methylparaben (MeP), ethylparaben (EtP), n-propylparaben, and n-butylparaben by LC-MS/MS in 63 breast milk samples from 54 Taiwanese mothers within six months postpartum, classified as colostrum (≤7 days) or post-colostrum milk (>7 days). Estimated daily intake (EDI) was calculated and compared with the EFSA group acceptable daily intake (ADI) of 10 mg/kg/day for MeP + EtP.

RESULTS: EtP and MeP were detected in 100% and 81% of samples. Both were significantly higher in colostrum than in post-colostrum milk (EtP: 6.35 vs. 1.6 ng/mL, p < 0.001; MeP: 0.75 vs. 0.5 ng/mL, p = 0.028). EtP levels exceeded those reported in Korean and Chinese cohorts. EDI for MeP + EtP was 0.36 μg/kg/day in colostrum-fed neonates-∼28,000-fold below the EFSA ADI-yet body-weight-normalised EtP exposure was ∼1.5-fold higher than in older infants.

CONCLUSIONS: Estimated paraben intake via breast milk was far below the EFSA group ADI, although a modest, transient increase in body-weight-normalised EtP exposure was observed during the colostrum period.

TRIAL REGISTRATION NUMBER: Not applicable.

PMID:42641861 | DOI:10.1016/j.fct.2026.116354

J Appl Toxicol. 2026 Aug 25. doi: 10.1002/jat.70405. Online ahead of print.

ABSTRACT

Neuroactive substances have emerged as potent endocrine disruptors affecting male reproductive health through central and peripheral mechanisms. Among these, benzodiazepines, which are widely used for the management of anxiety, insomnia, epilepsy, and neuromuscular disorders, are known as GABA A (gamma-aminobutyric acid type A) receptor positive allosteric modulators. These are traditionally believed to have central nervous system effects. However, recent experimental findings suggest that benzodiazepines may have peripheral effects through testicular homeostasis and the hypothalamic-pituitary-gonadal axis. This article aims to present an overview of experimental and clinical studies focusing on the potential harmful effects of benzodiazepines on male reproductive health, particularly concerning pharmacokinetics and neuroendocrine, cellular, and hormonal mechanisms Benzodiazepines have lipophilic characteristics, which means they remain longer in tissues and membranes, allowing them to accumulate in reproductive organs, which also have a lipophilic environment. Sustained modulation of inhibitory neural signaling may disrupt gonadotropin release, decrease testosterone synthesis, and impair testicular signaling pathways, ultimately compromising spermatogenesis. Some animal and in vitro studies suggest testicular changes, reduced testosterone levels, impaired sperm motility, and increased oxidative stress in reproductive cells. These changes may arise due to chronic exposure to benzodiazepines. Although some human studies are limited, the detection of benzodiazepines in seminal fluid and the association of drug use with altered sperm parameters remain under investigation in male reproductive health. Other studies indicate that benzodiazepines may also function as neuroendocrine disruptors, primarily impairing male fertility through central and peripheral mechanisms. However, further human studies are needed to understand the risks, the reversibility of the drug's effects, and the potential generational impacts. Well-designed longitudinal research is essential to determine dose dependency, reversibility, and possible transgenerational consequences of chronic benzodiazepine exposure.

PMID:42642070 | DOI:10.1002/jat.70405

Cureus. 2026 Jul 24;18(7):e113295. doi: 10.7759/cureus.113295. eCollection 2026 Jul.

ABSTRACT

Middle interhemispheric variant (MIH) of holoprosencephaly (HPE), also known as syntelencephaly, is a rare subtype of HPE characterized by abnormal midline connection of the posterior parts of the frontal lobes and the anterior parts of the parietal lobes with variable corpus callosum abnormalities. We report the case of a five-year-old girl with syntelencephaly presenting with a cleft lip and palate, developmental delay, cerebral palsy, and intermittent diabetes insipidus. Brain magnetic resonance imaging demonstrated the characteristic features of both syntelencephaly and septo-optic dysplasia, including midline fusion of the frontal and parietal lobes, partial agenesis of the corpus callosum with hypoplastic genu and splenium, absence of the septum pellucidum, and bilateral optic nerve hypoplasia. Additional radiologic findings included bilateral subependymal gray matter heterotopia, colpocephaly, and an azygos anterior cerebral artery. A literature search was conducted on PubMed and Google Scholar, with combinations of "middle interhemispheric variant" or "syntelencephaly" and "septo-optic dysplasia," "pituitary gland dysfunction," "endocrine dysfunction," or "optic nerve hypoplasia." To the best of our knowledge, this represents the first published case of MIH-variant HPE associated with all three criteria for septo-optic dysplasia, expanding the known phenotypic spectrum of these rare malformations. The co-occurrence of syntelencephaly and septo-optic dysplasia in this patient may reflect a shared disruption of midline forebrain development during the fourth to eighth weeks of gestation, when interhemispheric cleavage and hypothalamic-pituitary-optic development overlap temporally and depend on interconnected signaling pathways, including SHH, ZIC2, and the SOX family of transcription factors. Recognition of this association may prompt clinicians to evaluate patients with MIH variant HPE for features of septo-optic dysplasia, including optic nerve abnormalities and hypothalamic-pituitary dysfunction, and highlights the need for interdisciplinary clinical management and long-term surveillance in these patients.

PMID:42634678 | PMC:PMC13499987 | DOI:10.7759/cureus.113295

Ultrason Sonochem. 2026 Aug 22;133:108018. doi: 10.1016/j.ultsonch.2026.108018. Online ahead of print.

ABSTRACT

MXene-based sonocatalysis is an emerging advanced oxidation process for removing recalcitrant dyes, endocrine-disrupting compounds, and pharmaceuticals from water, where conventional treatment may achieve very limited removal by coagulation and chlorination. This review was motivated by the need to clarify how MXene structure, water quality, and ultrasound conditions control contaminant degradation, mineralization, stability, and practical applicability. We hypothesized that MXenes enhance sonochemical oxidation by promoting pollutant adsorption, cavitation, charge separation, and reactive oxygen species generation, particularly in engineered heterostructures. Recent studies were critically analyzed with respect to MXene composition and surface chemistry, ultrasound frequency and power, water-matrix effects, degradation mechanisms, hybrid sonophotocatalytic/sono-Fenton processes, mineralization, and catalyst reusability. MXene-based systems achieved up to >99% antibiotic removal, approximately 70% acetaminophen mineralization, and 80% rhodamine B degradation in 20 min; ^•OH and O₂^•- predominantly governed oxidation, while several catalysts retained more than 80-90% removal over five cycles and exhibited limited leaching. Overall, MXenes provide a versatile platform for efficient water purification by integrating conductive, adsorptive, cavitation-nucleating, and interfacial charge-transfer functions, although real-water validation, standardized evaluation, energy-efficient reactor scale-up, and toxicity assessment remain necessary for environmental deployment.

PMID:42636582 | DOI:10.1016/j.ultsonch.2026.108018

Ecotoxicol Environ Saf. 2026 Aug 24;323:120702. doi: 10.1016/j.ecoenv.2026.120702. Online ahead of print.

ABSTRACT

Maternal exposure to the plasticizer DEHP during gestation and lactation programs lasting sex-specific alterations in offspring intestinal health. This study investigated the transgenerational effects of perinatal DEHP exposure on offspring intestinal health using a C57BL/6 mouse model. Dams were exposed to 0, 40, or 400 ppm DEHP via their diet during gestation and lactation. We analyzed the growth phenotypes, intestinal histology, gut microbiota, and colonic transcriptomics of the offspring. We found that perinatal DEHP exposure did not affect the growth of dams or offspring but induced significant intestinal structural damage. In both male and female offspring, this damage manifested as reduced colon length and decreased colonic goblet cell counts. This common insult triggered strongly divergent downstream responses. Colonic transcriptomics revealed that female offspring displayed a robust defense characterized by the significant upregulation of xenobiotic metabolism pathways (e.g., the expression of the cytochrome P450 genes Cyp3a44 and Cyp3a25). Conversely, male offspring showed a muted transcriptional response skewed toward immune modulation. The gut microbiota was reshaped in a sex-dependent manner: male offspring exhibited increased microbial diversity and a decrease in Bacteroides species, whereas females showed enrichment of the mucin-degrading Akkermansia muciniphila. Integrated functional analysis predicted a male-biased shift toward host-microbe energy metabolism and a female-biased shift toward lipid and detoxification pathways. These findings demonstrate that maternal DEHP exposure compromises intestinal barrier integrity and establishes sexually dimorphic microbiota-host metabolic axes, providing a novel mechanism for the developmental programming of long-term disease susceptibility by environmental endocrine disruptors.

PMID:42636666 | DOI:10.1016/j.ecoenv.2026.120702

Comp Biochem Physiol C Toxicol Pharmacol. 2026 Aug 24;310:110665. doi: 10.1016/j.cbpc.2026.110665. Online ahead of print.

ABSTRACT

Dibutyl phthalate (DBP), an environmental endocrine disruptor, has been shown to pose potential risks for inducing cardiotoxicity, although its precise mechanism remains incompletely understood, and effective preventive strategies are lacking. Astaxanthin (AST), known for its potent antioxidant properties and potential cardiovascular protective effects, has garnered widespread attention. This study demonstrates that environmental concentrations of DBP cause cardiac dysfunction in zebrafish and reduce viability while increasing apoptosis in human cardiomyocytes (AC16), accompanied by elevated cardiac injury markers. Mechanistically, DBP induces mitochondrial oxidative stress (including increased ROS production, impaired antioxidant systems, and mitochondrial membrane potential and function disruption), leading to activation of the PINK1/Parkin pathway and excessive mitophagy. Intervention with AST alleviates oxidative stress, enhances mitochondrial function, and normalizes the overactivated mitophagy. Both in animal and cell models, AST exhibits significant cardioprotective effects. This study is the first to reveal that AST mitigates DBP-induced cardiotoxicity by regulating mitochondrial autophagy homeostasis, providing new insights into the molecular mechanisms of environmental pollutants-induced cardiovascular injury and potential therapeutic strategies.

PMID:42637184 | DOI:10.1016/j.cbpc.2026.110665

Environ Pollut. 2026 Aug 24:129016. doi: 10.1016/j.envpol.2026.129016. Online ahead of print.

ABSTRACT

Polyhalogenated carbazoles (PHCZs) are disinfection by-products formed during drinking water treatment and represent an important class of emerging contaminants. PHCZs can enter the human body through multiple exposure routes and pose potential health risks. However, their biotransformation pathways and toxic effects in humans remain insufficiently understood, and the underlying molecular mechanisms of toxicity are still unclear. This study focused on 1,3,6,8-tetrachloro-9H-carbazole (1,3,6,8-CCZ) and constructed an activation-metabolism-toxicity pathway using multiple computational strategies. The results indicated that 1,3,6,8-CCZ was a potent activator of the aryl hydrocarbon receptor (AHR). AHR underwent a distinct conformational change upon activation, leading to a stable non-covalent interaction between TYR322 and the ligand. During AHR translocation from the cytoplasm to the nucleus, significant conformational rearrangements occurred in the Dα and Cα helices and the C-terminal region. Furthermore, P450-mediated electrophilic addition to 1,3,6,8-CCZ exhibited strong regioselectivity, which was driven by the C-O distance and the C-O-Fe angle. Epoxidation and NIH shift were the main metabolic pathways. Endocrine disruption assessment showed that 1,3,6,8-CCZ and its hydroxylated metabolites bound to five endocrine receptors with high affinity. This study provides mechanistic insights into the metabolic fate and toxicological effects of exogenous compounds in humans.

PMID:42637120 | DOI:10.1016/j.envpol.2026.129016

Environ Sci Ecotechnol. 2026 Aug 11;33:100751. doi: 10.1016/j.ese.2026.100751. eCollection 2026 Sep.

ABSTRACT

Understanding the sediment-water partitioning of emerging contaminants is essential for assessing their mobility, persistence and ecological risks in river systems. However, the mechanisms driving large differences in partitioning behaviour across contaminant classes remain poorly resolved at the basin scale. Here we show that major emerging contaminant classes follow distinct mechanistic regimes in sediment-water partitioning. Analysis of a nationwide dataset comprising 5085 paired sediment-water records across China's major river basins reveals that antibiotics are predominantly controlled by molecular descriptors, per- and polyfluoroalkyl substances are strongly modulated by ion-mediated interfacial processes, and endocrine-disrupting chemicals exhibit synergistic regulation by molecular, geochemical and basin-scale factors. Integration with molecular dynamics simulations confirms these class-specific mechanisms at the molecular interface, while a multi-branch multi-head attention framework enables accurate prediction (R ² = 0.76-0.92) and spatially explicit mapping of high-accumulation versus high-mobility zones. By identifying class-specific mechanistic regimes, this work provides both improved predictive capability and a clearer mechanistic basis for basin-scale risk assessment of emerging contaminants.

PMID:42633142 | PMC:PMC13499102 | DOI:10.1016/j.ese.2026.100751

Environ Toxicol Pharmacol. 2026 Sep;126:105149. doi: 10.1016/j.etap.2026.105149. Epub 2026 Aug 23.

ABSTRACT

Phthalate esters (PAEs) are environmental pollutants with potential neuroendocrine effects, yet systematic comparisons across congeners remain scarce. We employed electrostatic potential analysis (ESP), network toxicology, molecular docking, and molecular dynamics with MM-PBSA (Molecular Mechanics Poisson-Boltzmann Surface Area) binding free energy calculations to evaluate six PAEs. Target prediction from public databases and neuroendocrine-related gene compilation yielded 176 common genes, identifying five hubs AKT1, ESR1, MAPK3, PPARG, and TNF-α. MM-PBSA binding energies ranged from -40.23 to -8.25 kcal/mol, with DINP binding strongest to ESR1 and DEHP exhibiting the highest affinities to PPARG and TNF-α. ESP revealed congener-specific surface properties, with DEP and DIBP exhibiting strong negative potentials on carbonyl oxygens, whereas DEHP and DINP were predominantly hydrophobic. We propose a tentative in silico hierarchy with DEHP > BBP ≈ DBP > DINP > DIBP > DEP. This work provides a theoretical basis for congener specific risk assessment of PAEs.

PMID:42633855 | DOI:10.1016/j.etap.2026.105149

Environ Int. 2026 Aug 18;215:110463. doi: 10.1016/j.envint.2026.110463. Online ahead of print.

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants that can disrupt human hepatic metabolism both directly and through alterations of the gut microbiota. However, the contribution of microbiota-mediated mechanisms to PFAS-induced hepatic dysfunction remains poorly understood. Here, we investigated how PFAS-modified gut microbial metabolites affect human hepatocyte metabolism using an in vitro colon fermentation model, supported by an in vivo mouse and in vitro human hepatocyte exposure studies. PFAS exposure altered the fecal metabolome in human colonic fermentations, particularly affecting pathways related to fatty acid, amino acid, vitamin, and mitochondrial metabolism. Fecal metabolomics from PFOA-exposed mice showed overlapping pathway-level alterations, including effects on fatty acid, bile acid, and steroid hormone metabolism, supporting the biological relevance of the in vitro findings. Exposure of HepaRG hepatocytes to control fermentation extracts markedly altered lipid profiles, confirming that gut-derived metabolites actively regulate hepatic metabolism. Notably, PFAS-exposed fermentation extracts induced distinct hepatocyte metabolic changes compared with PFAS-spiked control extracts, indicating effects driven by PFAS-modified microbial metabolites rather than direct PFAS carry-over. These changes included decreased acyl-carnitines and increased L-carnitine, consistent with altered fatty acid transport and mitochondrial β-oxidation. PFAS-modified extracts also altered bile acids, steroid metabolites, inosine, and sialic acid derivatives, suggesting broader alteration of bile acid signaling, endocrine-related metabolism, purine metabolism, glycoprotein turnover, and lipid-glucose homeostasis. These findings from our pilot study demonstrate that PFAS exposure reshapes gut microbial metabolite profiles with downstream consequences for hepatocyte metabolism. Our findings provide new mechanistic insight into how PFAS may contribute to metabolic disorders.

PMID:42632263 | DOI:10.1016/j.envint.2026.110463

Environ Sci Technol. 2026 Aug 17. doi: 10.1021/acs.est.6c07158. Online ahead of print.

ABSTRACT

Thyroid dysfunction affects hundreds of millions of people worldwide, yet the environmental contributors remain poorly characterized. Dibromoacetic acid (DBA), an unregulated brominated disinfection byproduct, is frequently detected in drinking water and is widely present in human populations. Despite its widespread human exposure, its potential to disrupt thyroid function and induce hypothyroidism has remained largely unexplored. To address this knowledge gap, we adopted an integrative strategy combining network toxicology, transcriptomics, and in vivo and in vitro experimental validation. Phenotypic results showed that in DBA-exposed SD rats, plasma thyroid hormone (TH) levels decreased, and thyroid histomorphology and ultrastructure were impaired. Mechanistically, DBA dysregulated thyroid miRNA expression, particularly upregulating miR-365-5p/miR-448-5p to downregulate SOCS1. Subsequently, SOCS1 depletion coupled with oxidative stress hyperactivated the Jak1/Stat1 signaling cascade, which, in turn, positively regulated YY1 to transcriptionally repress TPO in thyrocytes, ultimately suppressing TH synthesis. Moreover, DBA disrupted TH metabolism, transport, selenium trafficking, and receptor expression, further exacerbating the hypothyroidism. Taken together, our results identify DBA as an unrecognized thyroid-disrupting chemical beyond a simple unregulated drinking-water DBP. This integrative paradigm bridges computational prediction and mechanistic validation, establishing a reliable workflow to assess endocrine disruption triggered by poorly characterized DBPs and emerging environmental contaminants.

PMID:42632401 | DOI:10.1021/acs.est.6c07158

Comp Biochem Physiol C Toxicol Pharmacol. 2026 Aug 22;310:110662. doi: 10.1016/j.cbpc.2026.110662. Online ahead of print.

ABSTRACT

The widespread transmission of mosquito-borne diseases such as dengue, chikungunya, Zika, and yellow fever by Aedes albopictus necessitates environmentally sustainable vector control solutions. This study developed and characterized a citral-based nanoemulsion using Tween 80 via low-energy emulsification, aiming to enhance larvicidal efficacy and environmental safety. Larvicidal bioassays against third instar A. albopictus revealed significantly higher potency for citral nanoemulsion (LC₅₀: 18.886 mg/L; LC₉₀: 78.209 mg/L) compared to unformulated citral (LC₅₀: 25.777 mg/L; LC₉₀: 99.481 mg/L). Morphological study and SEM analysis demonstrated severe structural damage in nanoemulsion-treated larvae, including cuticle collapse, spiracle deformation, and anal gill disfigurement. Biochemical assays indicated elevated catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA) levels, suggesting oxidative stress induction. Molecular docking revealed moderate to high binding affinities of citral to CAT (-6.3 kcal/mol), SOD (-4.5 kcal/mol), acetylcholine receptor (AChR; -6.0 kcal/mol), and juvenile hormone-binding protein (JHBP; -7.0 kcal/mol), involving hydrogen bonding and hydrophobic interactions. These interactions imply multi-target disruption of antioxidant defence, neural signalling, and endocrine regulation, contributing to larval mortality. Environmental safety evaluation using Chironomus larvae showed low acute toxicity (<10% immobilization at 52.136 mg/L), indicating selective action toward target species. Collectively, the findings highlight citral nanoemulsion as a potent, biodegradable and target-specific larvicide with minimal non-target effects, aligning with sustainable mosquito control strategies. Future work should focus on field validation, adult mosquito susceptibility, and chronic ecological safety to facilitate large-scale application.

PMID:42632437 | DOI:10.1016/j.cbpc.2026.110662

Environ Toxicol Pharmacol. 2026 Aug 22;127:105146. doi: 10.1016/j.etap.2026.105146. Online ahead of print.

ABSTRACT

Parabens (PBs) are widely used preservatives in consumer products and suspected endocrine disruptors associated with adverse pregnancy outcomes. However, a structured framework for quantifying these risks is currently lacking. Employing the Targeted Risk Assessment of Environmental Chemicals (TRAEC) scheme, this study synthesized evidence from 16 epidemiological, 11 in vivo, and 5 in vitro studies, alongside our experimental data. PBs posed a moderate overall risk (score: 6.07), displaying compound-specific profiles. Regarding placental toxicity, methylparaben (MePB) scored highest (6.83), outranking ethylparaben (EtPB: 5.94), propylparaben (PrPB: 5.05), and butylparaben (BuPB: 3.17), whereas MePB (6.67) and BuPB (6.60) dominated birth outcome risks. Literature associated PBs with shortened gestation, restricted fetal growth, thyroid disruption, and metabolic alterations. Mechanistically, our in vitro human trophoblast models demonstrated that MePB and PrPB suppressed cellular proliferation, migration, and tube formation, driving placental insufficiency. These insights underscore the critical need to mitigate maternal PBs exposure to protect fetal-placental health.

PMID:42632608 | DOI:10.1016/j.etap.2026.105146

Food Res Int. 2026 Oct 31;242(Pt 2):119878. doi: 10.1016/j.foodres.2026.119878. Epub 2026 Jun 27.

ABSTRACT

Bisphenol A (BPA) and its analogs, bisphenol S (BPS) and bisphenol F (BPF), are endocrine-disrupting chemicals commonly migrating from epoxy linings in canned beverages, posing health risks such as reproductive disorders and metabolic issues. This study investigated BPA, BPS, and BPF migration from canned soft drinks sold in Turkiye, considering storage conditions (4 °C, 25 °C, 40 °C for 3-90 days) and pH effects, with human health risk assessment. The sample comprised eight products from local and international brands. Samples were stored under simulated conditions and extracted using an innovative magnetic solid-phase extraction (MSPE) with Fe-Al MMH@TiO2-CTAB sorbent (50 mg/20 mL sample, 45 s vortex, 1 mL acetonitrile desorption). Analysis was performed via HPLC-PDA. Method validation yielded LOD/LOQ of 0.02-0.05/0.06-0.15 μg/L, R² > 0.9908, intra-/inter-day %RSD 1.1-7.1%, and recoveries 80.2-118.9%. Migration levels (μg/L) increased with temperature and time, negatively correlating with pH (r = -0.28). BPA averaged 0.581 (max 2.20 in cola at 40 °C/90 days), BPS 0.026, BPF 0.052. Cola and fruit-flavored groups showed highest migration due to low pH (<3). Pearson correlations confirmed strong positive effects of duration (r = 0.77-0.81) and moderate for temperature (r = 0.34-0.43). Risk assessment revealed EDI 0.000056-0.00254 μg/kg/day, HQ 0.278-12.70, HI 5.33-14.44 (exceeding 1 in acidic groups), but LCR <10^{-10} (negligible cancer risk). Findings align with recent literature, emphasizing pH-driven migration in acidic beverages and the need for BPA-free linings. This study provides critical data for regulatory guidelines in emerging markets like Turkiye, where soft drink consumption exceeds 3.5 billion liters annually.

PMID:42632720 | DOI:10.1016/j.foodres.2026.119878

Front Med (Lausanne). 2026 Aug 7;13:1916744. doi: 10.3389/fmed.2026.1916744. eCollection 2026.

ABSTRACT

BACKGROUND: Endometriosis is an estrogen-dependent inflammatory disorder associated with pelvic pain, infertility, repeated treatment, and impaired quality of life. Thyroid dysfunction and thyroid autoimmunity are also common in reproductive-aged women and may affect menstrual cyclicity, ovarian function, implantation, pregnancy maintenance, and assisted reproduction. Observational studies suggest an association between thyroid-related phenotypes and endometriosis, but its directionality, reproductive relevance, and biological basis remain uncertain.

MAIN BODY: This narrative review synthesizes epidemiological, mechanistic, reproductive, environmental, genetic, and causal-inference evidence on the thyroid-endometriosis interface. It distinguishes biochemical thyroid function traits, thyroid dysfunction, thyroid autoimmunity, and diagnosis-based thyroid disease as separate but related constructs. Current evidence suggests that thyroid autoimmunity may be more relevant to endometriosis than isolated thyroid hormone abnormalities. Cohort, register-based, case-control, and infertility-population studies have reported associations with subsequent thyroid morbidity, thyroid autoantibody positivity, and assisted reproduction outcomes, although findings remain heterogeneous across populations, study designs, and phenotype definitions. Mechanistic evidence is best interpreted at three levels: established endometriosis biology, indirect thyroid-related reproductive plausibility, and shared upstream susceptibility involving endocrine-disrupting chemicals and genetic or epigenetic vulnerability. Direct thyroid-to-lesion evidence remains limited. Most available evidence is observational. A recent bidirectional Mendelian randomization study reported several phenotype-specific associations, but the estimates require independent replication and do not establish a uniform thyroid-to-endometriosis causal relationship.

CONCLUSION: The thyroid-endometriosis association is better viewed as a phenotype-specific reproductive immune-endocrine interface than as a simple thyroid hormone-driven causal pathway. Current evidence does not justify universal thyroid screening solely because endometriosis is present. Thyroid evaluation should instead follow established endocrine, reproductive, pregnancy-related, or autoimmune indications, including infertility, recurrent pregnancy loss, menstrual disturbance, planned assisted reproduction, symptoms of thyroid dysfunction, previous abnormal thyroid tests, or coexisting autoimmune disease. Future studies should combine standardized phenotyping, prospective follow-up, mechanistic biomarkers, and causal-inference methods to determine whether thyroid-related pathways are clinically useful markers, modifiable contributors, or parallel manifestations of systemic dysregulation in endometriosis.

PMID:42630383 | PMC:PMC13493568 | DOI:10.3389/fmed.2026.1916744

Environ Int. 2026 Aug 18;215:110463. doi: 10.1016/j.envint.2026.110463. Online ahead of print.

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants that can disrupt human hepatic metabolism both directly and through alterations of the gut microbiota. However, the contribution of microbiota-mediated mechanisms to PFAS-induced hepatic dysfunction remains poorly understood. Here, we investigated how PFAS-modified gut microbial metabolites affect human hepatocyte metabolism using an in vitro colon fermentation model, supported by an in vivo mouse and in vitro human hepatocyte exposure studies. PFAS exposure altered the fecal metabolome in human colonic fermentations, particularly affecting pathways related to fatty acid, amino acid, vitamin, and mitochondrial metabolism. Fecal metabolomics from PFOA-exposed mice showed overlapping pathway-level alterations, including effects on fatty acid, bile acid, and steroid hormone metabolism, supporting the biological relevance of the in vitro findings. Exposure of HepaRG hepatocytes to control fermentation extracts markedly altered lipid profiles, confirming that gut-derived metabolites actively regulate hepatic metabolism. Notably, PFAS-exposed fermentation extracts induced distinct hepatocyte metabolic changes compared with PFAS-spiked control extracts, indicating effects driven by PFAS-modified microbial metabolites rather than direct PFAS carry-over. These changes included decreased acyl-carnitines and increased L-carnitine, consistent with altered fatty acid transport and mitochondrial β-oxidation. PFAS-modified extracts also altered bile acids, steroid metabolites, inosine, and sialic acid derivatives, suggesting broader alteration of bile acid signaling, endocrine-related metabolism, purine metabolism, glycoprotein turnover, and lipid-glucose homeostasis. These findings from our pilot study demonstrate that PFAS exposure reshapes gut microbial metabolite profiles with downstream consequences for hepatocyte metabolism. Our findings provide new mechanistic insight into how PFAS may contribute to metabolic disorders.

PMID:42632263 | DOI:10.1016/j.envint.2026.110463

Fish Physiol Biochem. 2026 Aug 21;52(5):157. doi: 10.1007/s10695-026-01781-2.

ABSTRACT

Pharmaceutical contaminants are increasingly recognized as critical pollutants in aquatic ecosystems, with antiepileptic drugs such as carbamazepine (CBZ) frequently detected at environmentally relevant concentrations. This study evaluated the reproductive and endocrine-disrupting effects of CBZ in male and female Gambusia affinis. Fish were exposed to environmentally relevant (13 ng L^-1) and sublethal concentrations (2.4 and 4.8 mg L^-1) for 60 days. Reproductive indices, including gonadosomatic index, sperm quality parameters, fecundity, oocyte diameter, and histopathology, were assessed alongside hormonal variations (FSH, LH, testosterone, estradiol, cortisol), vitellogenin levels, and the concentrations of steroidogenic enzymes (3β-HSD, 17β-HSD, and aromatase). Results demonstrated that sublethal concentrations of CBZ significantly reduced sperm count, motility, and viability in males, while also decreasing fecundity and oocyte development in females. Hormonal disruption was evident, with decreased levels of FSH, LH, and testosterone in males and estradiol in females, alongside elevated cortisol. CBZ exposure increased aromatase and vitellogenin in males while reducing both in females, indicating feminization in males and impaired ovarian function in females. Histopathological alterations corroborated these findings, showing gonadal degeneration under chronic exposure. These results confirm that CBZ, even at low concentrations, poses a substantial risk to fish reproduction and endocrine homeostasis. The study highlights the necessity of monitoring pharmaceutical residues in freshwater ecosystems and their implications for fish population dynamics and ecological sustainability.

PMID:42627461 | DOI:10.1007/s10695-026-01781-2

Int J Mol Med. 2026 Oct;58(4):288. doi: 10.3892/ijmm.2026.5959. Epub 2026 Aug 21.

ABSTRACT

Osteoporosis is a systemic skeletal disease characterized by progressive bone loss and an increased risk of fracture, and it represents a major public health challenge worldwide. Osteoporosis has multiple pathogenic determinants, including age, endocrine disorders and medication. Current therapeutic approaches primarily aim to promote osteogenesis directly or inhibit osteoclast activity; however, these strategies may limit therapeutic efficacy and increase the risk of adverse effects. The present review provided an integrated perspective on the pathogenesis of osteoporosis from the standpoint of glucose metabolism. Glucose oxidation generates ATP and metabolic intermediates that are key to bone homeostasis. During early differentiation, mesenchymal stem cells rely predominantly on glycolysis during commitment toward pre‑osteoblasts, whereas maturation into functional osteoblasts depends more notably on oxidative phosphorylation. The fusion and differentiation of osteoclasts require robust mitochondrial oxidation. Lactate derived from anaerobic metabolism has a dual role in bone metabolism. High‑risk populations for osteoporosis include postmenopausal women, patients with type 2 diabetes mellitus and individuals with obesity. Estrogen exerts anti‑inflammatory and antioxidant effects through receptor activation. Excessive production of advanced glycation end‑products disrupts the bone matrix, whereas hyperlipidemia promotes inflammatory factor‑induced bone resorption. These pathological changes disrupt the insulin receptor substrate/PI3K/AKT signaling pathway, compromise glucose transporter‑mediated cellular glucose uptake and thus, contribute to relative insulin resistance and insufficiency compared with physiological states. In conclusion, the present review demonstrated that abnormal glucose metabolism is a key pathogenic mechanism in osteoporosis and that targeting insulin signaling may represent a fundamental strategy for correcting glucose metabolic abnormalities across diverse etiologies.

PMID:42627054 | PMC:PMC13502487 | DOI:10.3892/ijmm.2026.5959

Tissue Cell. 2026 Aug 17;104(Pt 2):103865. doi: 10.1016/j.tice.2026.103865. Online ahead of print.

ABSTRACT

The current study aimed to analyze the histological and endocrine changes caused by long-term administration of Boldenone (an anabolic steroid) on the ovaries and vagina of adult female albino rats, as well as the role of propolis. Forty adult female rats were divided into five groups: the Boldenone group received alternative injections (5 mg/kg b.wt/i.m.) once a week/8weeks; the Propolis group was given oral doses (100 mg/kg b.w. /daily) /8weeks, dissolved in distilled water; two control groups received vehicles; and the fifth group was co-treated with Boldenone and Propolis. After eight weeks, samples were collected for assessment, including hormonal assay, antioxidant biomarkers, Histomorphology, immunohistochemical reactivity, and histomorphometry. Boldenone significantly decreased the gonadosomatic index, serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol, as well as tissue total antioxidant capacity (TAC) and superoxide dismutase (SOD). Testosterone levels showed no difference, while Malondialdehyde (MDA) levels and rat final body weight increased significantly. The treatment also resulted in significantly reduced ovarian cortical diameter, vaginal wall thickness, number of primordial and developing follicles, an increase in the number of atretic follicles, and the interstitial gland area. Propolis mitigated the Boldenone-induced alterations, though it didn't significantly affect testosterone levels or vaginal mucosal thickness. Overall, Boldenone disrupted the endocrine hypothalamic-pituitary-ovarian axis and impaired female rat fertility, ovarian reserve, and caused vaginal atrophy. Cotreatment with propolis demonstrated strong, powerful protective antioxidant effects.

PMID:42628193 | DOI:10.1016/j.tice.2026.103865

Ecotoxicol Environ Saf. 2026 Aug 21;323:120689. doi: 10.1016/j.ecoenv.2026.120689. Online ahead of print.

ABSTRACT

Di-(2-ethylhexyl) adipate (DEHA), initially regarded as a safer alternative to Di-(2-ethylhexyl) phthalate (DEHP) phthalate plasticizer, is widely used in food packaging and consumer products. Despite its high detection levels in food and established human exposure, the health impacts of DEHA at environmentally relevant doses remain poorly understood. The main aim of this study was to investigate whether sub-chronic dietary exposure to DEHA disrupts metabolism homeostasis in female mice, and to clarify the underlying mechanism through combined in vivo and in vitro models. In this study, 27 four‑week‑old female C57BL/6 J mice with similar initial body weight were randomly assigned to four groups (control (n = 6), vehicle (n = 6), low‑dose DEHA (n = 7), and high‑dose DEHA (n = 8)), where the DEHA concentrations in the mice's diet were 0.087 and 18.2 mg/kg, respectively, for 15 weeks of sub-chronic exposure. DEHA significantly increased body weight, fat mass, fasting blood glucose, serum cholesterol and induced hepatic steatosis, without affecting food intake or energy expenditure. Untargeted metabolomics analysis identified a significant elevation of lipid metabolites in the liver tissues of DEHA-exposed mice. Further mechanistic studies demonstrated that DEHA upregulated the peroxisome proliferator-activated receptor gamma (PPARγ) signaling pathways and the expression of genes associated with endoplasmic reticulum (ER) stress. In both mouse alpha mouse liver 12 (AML12) and human liver-7702 (L02) hepatocytes, DEHA directly induced dose-dependent lipid accumulation. Pharmacological inhibition of ER stress with specific inhibitor 4-phenylbutyric acid (4-PBA) attenuated DEHA-induced lipid accumulation and lipogenic gene expression. These findings demonstrate that environmental-level DEHA exposure promoted obesity and hepatic steatosis in female mice by disturbing the PPARγ signaling pathway and upregulating ER stress-related genes, highlighting a significant and previously underappreciated health risk of DEHA in females and calling for a reassessment of its safety as an endocrine-disrupting chemical.

PMID:42628178 | DOI:10.1016/j.ecoenv.2026.120689

Talanta. 2026 Aug 20;312(Pt B):130488. doi: 10.1016/j.talanta.2026.130488. Online ahead of print.

ABSTRACT

Bisphenol A (BPA) and its structural alternatives are contaminants of concern due to their endocrine-disrupting properties and widespread human exposure. The progressive replacement of BPA by alternative bisphenols has increased the need for sensitive analytical methods capable of monitoring both regulated and emerging analogues in biological matrices. In this study, a fast analytical approach based on ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and ion mobility-high-resolution mass spectrometry (IM-HRMS) was developed for the determination and suspect screening identification of bisphenols in human urine. Following enzymatic deconjugation and solid-phase extraction, BPA and eight priority bisphenols were quantified by UHPLC-MS/MS. Method validation demonstrated excellent linearity (r² = 0.9976-0.9999), limits of quantification of 0.1 ng/mL, relative recoveries between 89.1 and 135.0%, and intermediate precision generally below 10.0%. Application of the method to urine samples from 25 healthy volunteers revealed widespread exposure to BPA, bisphenol S (BPS), and bisphenol F (BPF). To extend chemical coverage, the same extracts were analyzed by IM-HRMS-based suspect screening, leading to the identification of additional bisphenols, including bisphenol G (BPG) and bisphenol M (BPM). The integration of IM provided collision cross section (CCS) values and enabled the discrimination of structurally related and isobaric compounds, improving annotation confidence. Furthermore, new experimental CCS reference values were established for bisphenol E (BPE), BPG, and BPM, expanding the currently available database for bisphenol characterization. The proposed approach provides a comprehensive strategy for monitoring human exposure to both of known and emerging bisphenols and supports future biomonitoring and risk assessment studies.

PMID:42628448 | DOI:10.1016/j.talanta.2026.130488

J Steroid Biochem Mol Biol. 2026 Aug 21;265:107104. doi: 10.1016/j.jsbmb.2026.107104. Online ahead of print.

ABSTRACT

Polycystic ovary syndrome (PCOS) is a common endocrine disorder influenced by genetic and environmental factors, yet the molecular mechanisms linking endocrine-disrupting chemicals (EDCs) to ovarian dysfunction remain unclear. Here, we establish a letrozole-induced PCOS-like rat model and integrate bulk RNA-seq, single-cell RNA-seq of human granulosa cells (GCs), and functional validation to identify CBX2 as a critical epigenetic regulator connecting EDC exposure to PCOS pathogenesis. Transcriptomic profiling revealed dysregulated cell cycle progression, disrupted cholesterol homeostasis, and chronic inflammation in PCOS ovaries. Of these, cholesterol biosynthesis genes (e.g., Ebp, Dhcr7) were broadly suppressed, while efflux (Abca1) and metabolism-related (Cyp27a1) genes showed opposing alterations. Cross-species analysis identified CBX2 as consistently upregulated in both rat and human PCOS GCs, where it strongly correlated with accelerated cell proliferation and impaired cholesterol homeostasis. Mechanistically, exposure to EDCs (BPA and DDT) significantly induced CBX2 expression in human GCs. ChIP-seq analysis demonstrated that CBX2 directly binds to and represses genes from cholesterol-homeostasis-associated transcriptional networks-including CSRNP1, DDIT3, and FOSL1-through H3K27me3-mediated epigenetic silencing. Functional validation showed that CBX2 knockdown suppressed GCs proliferation, reduced lipid droplet accumulation while restoring normal cell cycle distribution. Single-cell RNA-seq confirmed elevated CBX2 activity specifically in PCOS GCs, particularly during G2/M phase, where it exhibited the strongest negative correlation with cholesterol homeostasis signatures (rs = -0.23). These findings reveal a novel EDC-CBX2-H3K27me3 epigenetic axis that decouples GC proliferation from metabolic support functions, establishing CBX2 as both a molecular biomarker and potential therapeutic target for environment-associated PCOS.

PMID:42628813 | DOI:10.1016/j.jsbmb.2026.107104

Front Endocrinol (Lausanne). 2026 Aug 6;17:1838976. doi: 10.3389/fendo.2026.1838976. eCollection 2026.

ABSTRACT

INTRODUCTION: Anogenital distance (AGD) and penile length (PL) are considered as surrogate biomarkers of fetal androgen action and are used to study the impact of prenatal exposure to endocrine disrupting chemicals. Data for newborn sex-specific references of both AGD and PL are currently scarce for the Italian population. This study aimed to provide normative data in a large group of Italian newborns and to assess any associations with anthropometric parameters.

METHODS: Data were collected at birth in mother-infant dyads from April 2021 to September 2022. Four hundred and sixty-two/675 neonates at term of uncomplicated pregnancies were enrolled from three different Italian Hospitals. Newborns were divided in 5 subgroups according to weeks of gestational age(GA):1(37-37 + 6d w),2(38-38 + 6d w),3(39-39 + 6d w),4(40- 40 + 6d w),5(> 41w) and in 4 sub-groups according to birth weight (BW): A(2501-3000 g), B(3001-3500 g), C(3501-4000 g), D (>4001 g). Trained staff measured AGD and PL in newborns with an analogical caliper using the TIDES method. Anogenital distances (AGDs) considered were: ano-scrotal (AGD_AS) and ano-penile (AGD_AP) in males, ano-fourchette (AGD_AF) and ano-clitoral (AGD_AC)in females. Correlations among AGDs and anthropometric measures were evaluated by Pearson correlation analysis. P<0.05 was significant. Data were expressed as mean± standard deviation.

RESULTS: Overall, in males AGDs were longer than in females. Considering the 5 subgroups for GA, AGD_AP was significantly longer than AGD_AC in neonates born at and after 40 weeks(p<0.05) whereas AGD_AS was significantly longer than AGD_AF in neonates born at and after 39 weeks(p<0.05). AGD_AS increased with increasing GA. Considering AGDs according to BW, AGD_AP was significantly longer than AGD_AC in newborns with a BW between 3001 and 4000 g(p<0.05), whereas AGD_AS was significantly longer than AGD_AF in newborns with a BW between 2501 g and 4000 g(p<0.05). Mean PL of male newborns (N = 208) was 24.4 ± 6.83 mm and increased with GA. In the correlation analysis a positive significant correlation was found between AGD_AS and PL (r=0.576, p<0.001).

CONCLUSION: This study provided measurements and reference values for AGD and PL, based also on GA and BW, in a large group of newborns, supplying a valid well-reproducible instrument for clinical practice and the basis for further studies.

PMID:42625712 | PMC:PMC13489917 | DOI:10.3389/fendo.2026.1838976

Chem Biol Interact. 2026 Aug 21:112311. doi: 10.1016/j.cbi.2026.112311. Online ahead of print.

ABSTRACT

Triclosan (TCS) is a broad-spectrum antimicrobial agent that has raised public health concerns due to its continuous environmental release and human exposure. Previous studies suggest that TCS may disrupt endocrine function. Nonetheless, the toxicological effects on the female reproductive system, notably on ovarian granulosa cells, and the underlying pathways remain poorly understood. This study was designed to examine the toxic effects of TCS on human granulosa cells and the related mechanisms. To this end, human granulosa cell lines (KGN and SVOG) were treated in vitro with varying doses of TCS. The results demonstrated that TCS exposure led to marked cytotoxicity and DNA damage in a dose-dependent manner. Transcriptomic profiling showed that TCS markedly affected pathways associated with mitochondrial respiratory chain function and DNA repair mechanisms within granulosa cells. Subsequent mechanistic studies revealed that TCS led to mitochondrial dysfunction, as evidenced by reduced activity of mitochondrial respiratory chain complex I and a marked increase in mitochondrial ROS levels. Application of the mitochondria-targeted antioxidant MitoTEMPOL significantly alleviated the ROS accumulation and DNA damage induced by TCS. Specifically, we found that TCS exposure suppressed the synthesis of glutathione (GSH), a key component of the endogenous antioxidant defense system. The decline in GSH synthesis was further confirmed to be an upstream initiating factor for TCS-induced mitochondrial ROS production and DNA damage in granulosa cells, as evidenced by glutathione monoethyl ester (GSH-MEE) pretreatment. These findings reveal a previously unrecognized molecular mechanism by which TCS impairs ovarian reserve function, thereby providing important theoretical insights for assessing the reproductive toxicity risk of TCS and suggesting that antioxidants targeting GSH and mitochondria may represent a potential intervention strategy.

PMID:42628895 | DOI:10.1016/j.cbi.2026.112311

Adv Ther. 2026 Aug 22. doi: 10.1007/s12325-026-03758-2. Online ahead of print.

ABSTRACT

Menopause is associated with unfavorable metabolic changes that may contribute to the development of metabolic dysfunction-associated steatotic liver disease (MASLD), chronic kidney disease (CKD), and increased cardiometabolic risk. Within the evolving cardiovascular-kidney-metabolic (CKM) framework, MASLD is increasingly recognized as a key driver rather than an outcome of metabolic dysfunction. The liver and kidneys closely interact to regulate metabolism, detoxification, ketogenesis, and endocrine signaling, which together influence whole-body metabolic homeostasis. Menopause and the menopausal transition may modify these interactions through alterations in body fat distribution, insulin sensitivity, inflammatory signaling, and hepatic and renal physiology, thereby contributing to disruption of the increasingly recognized liver-kidney-metabolic (LKM) axis. Advanced MASLD, owing to liver fibrosis, may further accelerate CKD through systemic insulin resistance, subclinical inflammation, gut dysbiosis, and accumulated nephrotoxic metabolites. Menopausal hormone therapy (MHT) may partially mitigate these alterations; however, its effects on the LKM axis are variable and context-dependent according to timing, formulation, route of administration, and baseline metabolic phenotype. Current evidence does not support the use of MHT for the prevention or treatment of MASLD or CKD, and treatment should be guided by established indications. Understanding menopause as a systems-level modifier of LKM health may therefore support more personalized preventive and therapeutic strategies targeting CKM health in peri- and postmenopausal women through a holistic and integrated approach.

PMID:42629533 | DOI:10.1007/s12325-026-03758-2

Insect Biochem Mol Biol. 2026 Aug 21;195:104663. doi: 10.1016/j.ibmb.2026.104663. Online ahead of print.

ABSTRACT

Aedes aegypti is a major vector of arboviruses that pose major threats to global public health. In female mosquitoes, the fat body governs nutritional metabolism and vitellogenesis after a blood meal, with its functional state directly determining fecundity. Although endocrine and nutritional signals regulating mosquito reproduction have been widely studied, the role of non-coding RNAs (ncRNAs) and competing endogenous RNA (ceRNA) networks in fat body metabolic homeostasis remains poorly understood. To address this, we performed whole-transcriptome sequencing of fat bodies from sugar-fed and blood-fed females and identified 30 circRNAs, 142 miRNAs, 874 lncRNAs, and 4362 differentially expressed mRNAs, with significant enrichment in nutrient metabolism, energy homeostasis, and mTOR/MAPK signaling. Based on these data, we constructed ceRNA networks centered on blood-responsive miRNAs. Focusing on the downregulated, high-abundance aae-miR-283, we generated a transgenic overexpression line and found that elevated aae-miR-283 markedly impaired ovarian development, oviposition, and egg hatching. Mechanistically, dual-luciferase reporter assays confirmed that aae-miR-283 directly binds to the 3'UTR of ApoLp-Ⅱ/Ⅰ, supporting ApoLp-Ⅱ/Ⅰ as a direct target of aae-miR-283. The lncRNA MSTRG.88121.1 also showed binding to aae-miR-283 in the dual-luciferase reporter assay, suggesting that it may participate in an aae-miR-283-associated regulatory network. Functional studies revealed that both aae-miR-283 overexpression and ApoLp-Ⅱ/Ⅰ knockdown disrupted lipid homeostasis, increasing triacylglycerol accumulation in the fat body while depleting ovarian lipid stores, supporting a role for aae-miR-283-ApoLp-Ⅱ/Ⅰ regulation in lipid transport from the fat body to the ovaries. Our findings reveal a novel aae-miR-283-centered regulatory mechanism controlling reproductive energy allocation in Ae. aegypti and provide potential molecular targets for metabolic intervention-based vector control strategies.

PMID:42628881 | DOI:10.1016/j.ibmb.2026.104663

Ecotoxicology. 2026 Aug 20;35(7):155. doi: 10.1007/s10646-026-03140-6.

ABSTRACT

Environmental changes caused by anthropogenic activities are accompanied by a multitude of chemical compounds and stressors, which exert significant pressure on native anuran communities. Many of these substances are endocrine disruptors, which interfere with the organism's physiology, particularly the immune and reproductive systems. We used 49 male Leptodactylus fuscus collected in agricultural areas (soybean and sugarcane) and urban environments in the states of Goiás and São Paulo (Brazil) and compared them with each other and with minimally affected specimens from an environmental conservation unit (Emas National Park - Goiás). In the anthropized areas, there was an increase in the number of lymphocytes and neutrophils. The spleen of specimens collected in the different anthropized environments showed a decrease in white pulp, an increase in red pulp, an increase in mast cells, and a change in melanin pigmentation. In animals exposed to greater environmental disturbance, there was a tendency for an increase in the area occupied by spermatogonia, spermatocytes, spermatids, and spermatozoa. These results indicate that landscape anthropization is associated with multi-systemic physiological modifications, highlighting the role of tissue biomarkers in monitoring wild populations of L. fuscus under environmental stress.

PMID:42622724 | PMC:PMC13493454 | DOI:10.1007/s10646-026-03140-6

Toxicol Appl Pharmacol. 2026 Aug 20:118015. doi: 10.1016/j.taap.2026.118015. Online ahead of print.

ABSTRACT

The pesticide p,p'-DDT (DDT) and its analogs (p,p'-DDD, o,p'-DDD, and p,p'-DDE) inhibit the binding of dihydrotestosterone (DHT) to the androgen receptor (AR) and estradiol (E2) to the estrogen receptor (ERα) ligand-binding domains (LBDs), as previously reported. In this study, we introduce assays to measure the release of receptor-bound steroids. These compounds induced the release of DHT from the AR LBD and E2 from the ERα LBD. These findings suggest that DDT and its analogs may interact with a surface site on the LBD, thereby allosterically disrupting steroid binding. One potential site is binding function 3 (BF3). To explore this possibility, ligand docking studies were performed. The results revealed a correlation between interaction energy at the BF3 site and compound potency in the steroid release assay. Specific AR residues-Asn833, Phe673, and Pro723-appear to play key roles in ligand interaction with the BF3 site. In ERα, Met315, Val478, Lys481, and Pro365 are likely important for compound binding. Two residue pairs (Asn833 and Pro723 in AR and Val478 and Pro365 in ERα) occupy topologically equivalent positions within the BF3 sites, suggesting a conserved interaction mode across receptors. Based on these results we speculate that DDT and its analogs may act as endocrine-disrupting chemicals by modulating receptor activity through an allosteric mechanism involving the BF3 site.

PMID:42624378 | DOI:10.1016/j.taap.2026.118015

Toxicol Sci. 2026 Aug 20:kfag111. doi: 10.1093/toxsci/kfag111. Online ahead of print.

ABSTRACT

Adipose tissue plays a critical role in metabolic and endocrine function because it is essential for maintaining systemic energy homeostasis and other related physiological functions. Mammals have four types of adipose tissue: white adipose tissue (WAT), brown adipose tissue (BAT), beige or brite adipose tissue (BeAT), and pink adipose tissue (PAT). These adipose tissues release endocrine factors that modulate diverse processes such as energy storage and expenditure, appetite control, glucose homeostasis, insulin sensitivity, inflammation, lipid metabolism, tissue repair, thermogenesis, and milk production. Proper adipose tissue function relies on hormone receptors and signaling pathways that make the adipose tissues susceptible to disruption by endocrine-disrupting chemicals such as phthalates. Here, we review relevant research on the associations between phthalate exposures and abnormalities in WAT and BAT functions, including phthalate-induced changes in morphology, physiology, and gene expression effects. This review covers in vitro studies, in vivo studies in mammals, and studies in humans. We also discuss important gaps in the literature. Overall, the evidence indicates that phthalates adversely affect WAT and BAT functions. Further studies are needed to better elucidate the mechanisms through which phthalates act in the adipose tissues and to determine the effects of phthalates on human adipose tissues.

PMID:42623126 | DOI:10.1093/toxsci/kfag111

Metabolomics. 2026 Aug 20;22(5):139. doi: 10.1007/s11306-026-02513-6.

ABSTRACT

INTRODUCTION: Bisphenol A (BPA) is a widely distributed endocrine-disrupting chemical with documented metabolic effects in experimental models. Although hepatic transcriptional alterations following BPA exposure have been reported, the extent to which these changes translate into functional metabolic remodeling remains unclear.

OBJECTIVES: This study aimed to characterize global hepatic metabolomic alterations following chronic exposure to BPA at the lowest observed adverse effect level (LOAEL) in mice and to determine whether the affected metabolic networks overlap with pathways implicated in non-alcoholic fatty liver disease (NAFLD) progression and early events associated with hepatocarcinogenic susceptibility.

METHODS: Untargeted liquid chromatography-mass spectrometry (LC-MS)-based metabolomics was performed on liver samples from BPA-exposed (n = 8) and control (n = 6) mice. Differential metabolite analysis and pathway enrichment analysis were conducted to identify significantly altered metabolites and metabolic pathways.

RESULTS: BPA exposure induced marked hepatic metabolic remodeling involving polyunsaturated fatty acids, arachidonic acid-derived eicosanoids, lysophospholipids, retinoid metabolism, and phase II detoxification pathways. Dysregulation of omega-3 and omega-6 fatty acids and altered prostaglandin and thromboxane derivatives indicated disruption of inflammatory lipid mediator balance. Changes in retinol- and retinoic acid-related metabolites suggested impaired differentiation-associated signaling, while increased sulfated and glucuronidated metabolites reflected enhanced xenobiotic metabolism. Pathway enrichment analysis highlighted biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, and retinol metabolism as significantly affected pathways.

CONCLUSION: Chronic BPA exposure at a LOAEL dose induces coordinated hepatic metabolic reprogramming characterized by pro-inflammatory lipid remodeling, disruption of retinoid signaling, and activation of detoxification mechanisms. These alterations may represent metabolic features associated with pathways relevant to NAFLD progression and hepatocarcinogenic susceptibility.

PMID:42622901 | PMC:PMC13493429 | DOI:10.1007/s11306-026-02513-6

Environ Int. 2026 Aug 17;215:110467. doi: 10.1016/j.envint.2026.110467. Online ahead of print.

ABSTRACT

Several plastic-associated chemicals (PACs), such as bisphenols and phthalates, are endocrine disruptors. There is little research concerning PAC presence on vulvar skin or in underwear fabric, which remains in prolonged daily contact with thinly keratinised regions of the vulva. We measured PAC concentrations in commercially purchased women's underwear and detected several PACs in 100% of samples; polyamide fabric had higher concentrations of dimethyl phthalate (DMP), diethyl phthalate (DEP), and bisphenol S (BPS) compared to cotton. Di(2-ethylhexyl) phthalate (DEHP) was the dominant PAC in both fabric types. We collected skin swabs from the thighs and the outer vulva of adult women volunteers and investigated PAC distribution frequencies and concentrations. Bisphenol A (BPA) and DMP were not detected while BPS, DEP, DEHP, and di-n-decyl phthalate (DnDP) were detected in ∼ 50% to 100% of samples. There was a significant positive correlation between PAC lipophilicities and molecular weights with concentrations in skin-swabs. Estimated daily exposure (ng/kg bw/day) calculated for individual PACs did not exceed established limits for human exposure. BPA and DEHP decreased epidermal thickness in 3D keratinocyte-fibroblast organotypic raft co-cultures. This is the first report on PACs on vulvar skin and suggests that further robust studies to clarify vulvar dermal PAC absorption and links to vulvar dermatoses are warranted.

PMID:42623786 | DOI:10.1016/j.envint.2026.110467

Int Dent J. 2026 Aug 20;76(5):109791. doi: 10.1016/j.identj.2026.109791. Online ahead of print.

ABSTRACT

OBJECTIVES: Periodontitis is a chronic inflammatory disease contributing to systemic metabolic imbalances. Adipose tissue functions as an endocrine organ, releasing adipokines that influence insulin resistance and energy homeostasis. These mediators, such as visfatin, leptin, or adiponectin, may be modulated by periodontal inflammation. This review aims to synthesize current evidence on salivary adipokine levels in periodontitis and to assess the impact of nonsurgical periodontal treatment (NSPT) on these biomarkers.

METHODS: A systematic review was conducted across PubMed, Cochrane Library, and Web of Science (April 2025), following PRISMA guidelines. Studies were included if they assessed salivary levels of adipokines (visfatin, adiponectin, leptin, vaspin, adipsin, resistin) before and after NSPT in periodontitis patients. Risk of bias was assessed using the Cochrane Risk of Bias tool, version 2 (RoB2), for randomized controlled trials, and the Newcastle-Ottawa scale for nonrandomized studies.

RESULTS: Fifteen studies were included. Visfatin consistently significantly decreased after NSPT, suggesting a potential mechanistic link between periodontal inflammation and systemic metabolic pathways. Results for leptin, resistin, and adiponectin were less clear.

CONCLUSION: Salivary visfatin levels consistently decreased following NSPT across all nine studies reporting this outcome. However, this signal is based on very low-certainty evidence. These findings are therefore hypothesis-generating and should not be interpreted as establishing a causal relationship between periodontal inflammation and systemic metabolic dysregulation. Further methodologically rigorous studies are warranted to determine whether changes in salivary visfatin reflect a clinically meaningful systemic effect or represent a local inflammatory phenomenon.

CLINICAL RELEVANCE: Salivary adipokine variations in periodontitis - even without metabolic disorders - suggest that periodontal inflammation could potentially disrupt systemic metabolic balance. This highlights that periodontitis is not only a local disease and that controlling inflammation may help prevent systemic metabolic repercussions.

PMID:42624033 | DOI:10.1016/j.identj.2026.109791

Environ Pollut. 2026 Aug 20:128999. doi: 10.1016/j.envpol.2026.128999. Online ahead of print.

ABSTRACT

Nanoplastics (NPs) are increasingly recognised as ubiquitous environmental pollutants, and evidence continues to mount that humans are exposed to NPs primarily through food and drinking water. Whilst their presence in biological systems is well documented, their role in metabolic dysfunction remains unclear. Metabolic disorders such as obesity, insulin resistance and non-alcoholic fatty liver disease are characterised by chronic inflammation, impaired energy metabolism and endocrine disruption; under these conditions, the metabolic system itself is subjected to a state of persistent stress. Existing evidence suggests that NPs may directly induce metabolic disorders. However, their impact on metabolism appears to depend heavily on host susceptibility. We therefore propose, as a working hypothesis, the 'metabolic vulnerability amplification model', which posits that NPs do not act merely as independent metabolic toxins, but may amplify pre-existing metabolic stress. In this review, we integrated evidence at the molecular, cellular and organ levels, focusing on mitochondrial dysfunction, chronic inflammation and endocrine disruption, to examine metabolic abnormalities caused by NPs at a systems level. Furthermore, we summarise emerging mitigation strategies, highlight key knowledge gaps relating to chronic low-dose exposure and in vivo dose profiling, and outline priorities for future research. Overall, this study suggests that, under specific conditions of exposure and host susceptibility, NPs may compromise metabolic resilience.

PMID:42624238 | DOI:10.1016/j.envpol.2026.128999

Front Public Health. 2026 Aug 5;14:1909278. doi: 10.3389/fpubh.2026.1909278. eCollection 2026.

ABSTRACT

Food packaging and other food contact materials are increasingly recognized as sources of dietary chemical exposure. Among the compounds that may migrate from packaging into foods, several classes are relevant to breast cancer nutrition because they can act as endocrine-disrupting chemicals, including bisphenols, phthalates, per- and polyfluoroalkyl substances, and selected non-intentionally added substances generated during food-contact material manufacture or use. These exposures do not replace established nutritional determinants of breast cancer outcomes, such as dietary quality, body weight, physical activity, and metabolic health. Rather, they represent an overlooked dimension of the food environment that may intersect with estrogen signaling, adipose inflammation, oxidative stress, epigenetic regulation, and treatment-related survivorship needs. Evidence linking packaging-derived endocrine disruptors to breast cancer remains heterogeneous and is strongest for mechanistic plausibility and exposure biology, while epidemiologic associations vary across compounds, timing of exposure, biomarkers, and tumor subtypes. This Mini Review synthesizes current evidence on food packaging-derived endocrine disruptors in relation to breast cancer nutrition, with emphasis on dietary exposure pathways, estrogen-related mechanisms, and practical survivorship implications. We propose that nutrition guidance for breast cancer survivors should include low-burden strategies to reduce avoidable food-contact chemical exposure, without promoting restrictive or anxiety-inducing dietary behavior. Future research should integrate dietary assessment, packaging-use patterns, biomonitoring, endocrine-metabolic biomarkers, and breast cancer outcomes to clarify modifiable exposure windows and prevention opportunities.

PMID:42621883 | PMC:PMC13487656 | DOI:10.3389/fpubh.2026.1909278

Environ Toxicol. 2026 Aug 20. doi: 10.1002/tox.70185. Online ahead of print.

ABSTRACT

Pharmaceutical pollution of freshwater ecosystems is an emerging environmental and public-health issue in India. The high drug consumption in the country, along with the presence of concentrated manufacturing hubs, inadequate wastewater treatment, and weak monitoring systems, is leading to rising pollutant release. This review summarizes the existing evidence on pharmaceutical contaminants in Indian freshwaters with the focus on classes of pollutants, sources of contamination, environmental fate, toxicological pathways, ecological risks and remediation strategies. Antibiotics, non-steroidal anti-inflammatory drugs, stimulants and anticonvulsants are identified in the review as priority contaminant groups owing to their frequent detection, high use volume, environmental persistence and ecotoxicological relevance. These residues can enter freshwater systems through discharges from pharmaceutical manufacturing, hospital effluents, domestic wastewater, livestock runoff and agricultural pathways. Their persistence is due to their physicochemical properties, adsorption to sediment, incomplete biodegradation and limited removal in conventional wastewater treatment plants. Toxicological evidence points to risks of selection for antibiotic resistance, endocrine disruption, neurotoxicity, oxidative stress, reproductive impairment, genotoxicity and bioaccumulation in aquatic food webs. The review also covers microbial degradation, phytoremediation, constructed wetlands and advanced oxidation processes as remediation options and points out that the choice of technology should be context specific for industrial, municipal and natural water systems. This review offers a novel India-centric synthesis that links pharmaceutical production, consumption, environmental occurrence, ecological effects and remediation feasibility into an integrated framework for monitoring, policy reform and future research.

PMID:42622407 | DOI:10.1002/tox.70185

Biol Trace Elem Res. 2026 Aug 19. doi: 10.1007/s12011-026-05304-1. Online ahead of print.

ABSTRACT

BACKGROUND: Exposure to toxic metals has become a major environmental and public health concern due to its adverse effects on reproductive health. Recent evidence indicates that, beyond their direct toxicity, toxic metals can disrupt the homeostasis of essential trace elements that are critical for maintaining normal reproductive function. This review aims to examine the role of toxic metal-induced trace element imbalance in reproductive dysfunction and to elucidate the underlying mechanisms linking metal exposure to impaired fertility.

METHODS: Relevant experimental, epidemiological, and clinical studies investigating the effects of lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As), and chromium (Cr) on reproductive health were comprehensively evaluated. We conducted a structured narrative literature search of PubMed, Scopus, Web of Science, and Google Scholar for relevant publications published between 2000 and March 2025. The study included original research articles, systematic reviews and meta-analyses investigating toxic metal induced reproductive dysfunction and trace elements dysregulation in the body.

RESULTS: Current evidence demonstrates that toxic metals interfere with the absorption, transport, distribution, and biological functions of essential trace elements by competing for transporters, binding proteins, and intracellular targets. Cd, Pb, Hg, As, and Cr are considered as the most frequently studied environmental toxic metals in association with reproductive impairment. Combinedly these metals disturb the homeostasis of important trace elements and interfere with reproductive functions by several convergent pathways such as induction of oxidative stress and dysfunction of mitochondrial, endocrine impairment, inflammation, induction of apoptosis and DNA damage, epigenetic modulation, and etc.In males, toxic metal exposure is associated with impaired testicular development, altered steroidogenesis, reduced sperm quality, decreased sperm motility, and compromised fertility. In females, it contributes to ovarian dysfunction, menstrual irregularities, implantation failure, pregnancy complications, and adverse fetal outcomes. Among the affected trace elements, zinc and selenium play particularly important protective roles through their involvement in antioxidant defense, genomic stability, mitochondrial function, and endocrine regulation.

CONCLUSIONS: Trace element Dyshomeostasis represents a central mechanism linking toxic metal exposure to reproductive impairment. Present evidence indicates the similarity of mechanism of reproductive physiology modulation by cadmium, lead, mercury, arsenic and chromium involving oxidative stress, interfering hormonal axis, impairing mitochondria functions, inflammation, apoptosis and changing trace element metabolism. Detailed knowledge about this common process needs to enable efficient prevention strategies and effective treatments.

PMID:42616295 | DOI:10.1007/s12011-026-05304-1

Environ Sci Pollut Res Int. 2026 Aug 19. doi: 10.1007/s11356-026-38145-5. Online ahead of print.

ABSTRACT

Microplastic fibers (MPF) are released into the environment through washing synthetic fabrics. Other sources of microplastic (MP) particles include the decomposition of large-scale plastic waste, agricultural practices, plastic litter, and the use of personal care products. These persistent pollutants accumulate in both terrestrial and aquatic environments, posing a serious threat to the environment and human health. The bioaccumulation of fibers from contaminated food, water, and air can lead to chronic health problems, highlighting the importance of understanding their potential health impacts. Therefore, this review measured the potential risks of exposure to MPFs and MP particles for both humans and animals and assessed their effects on the digestive system and potential cancer risk. The review results indicated that MPFs and MP particles damage vital organs such as the stomach, liver, spleen, and pancreas, interfering with digestion and inhibiting nutrient absorption. MPs act as non-mutagenic co-carcinogens by increasing cell division, interfering with endocrine function and down-regulating DNA repair. MPFs promote carcinogenic processes through mechanisms such as oxidative stress, DNA damage and chronic inflammation while also facilitating the transport of toxic substances. By disrupting the digestive process, aiding the carriage of toxins and promoting carcinogenic processes, MPFs and MP particles impose serious health risks on both humans and animals. These findings emphasize the urgent need for efficient mitigation strategies to reduce their environmental presence and associated health impacts.

PMID:42616260 | DOI:10.1007/s11356-026-38145-5

Biometals. 2026 Aug 19. doi: 10.1007/s10534-026-00868-w. Online ahead of print.

ABSTRACT

Advancements in human activities lead to the widespread release of heavy metals into the environment. Zinc, iron, and nickel are heavy metals (HMs) that are teratogenic, carcinogenic, mutagenic, and endocrine disruptors when present at elevated concentrations. A greenhouse study was conducted in a hydroponic setup to investigate the phytoremediation potential of Chrysopogon zizanioides for the removal of zinc, iron, and nickel from aqueous media. The Vetiver grass was exposed to different concentrations of HMs for 15 days, and the samples were collected on the 3rd, 6th, 9th, 12th, and 15th days. The HM accumulation along with the biochemical variation was analysed to assess the plant stress and tolerance. The Vetiver grass shows an average absorption percentage of 52.91% for iron, 38.47% for nickel, and 45.16% for zinc. The biochemical analysis reveals increased phenol and proline content along with decreased carbohydrate, cellulose, and chlorophyll content. The Metal-ion binding site prediction (MIB) docking provides valuable insight into metal-ion-protein interactions. Analysing these interactions through docking contributes to metal homeostasis, transport, and detoxification of heavy metals, offering potential application in phytoremediation. As per the detailed Scopus survey, this is a ground-breaking work documenting metal-plant protein docking during phytoremediation that contributes to advancing sustainable environment strategies. This study advocates for the natural purification of water devoid of chemical interference. Subsequent genetic and agronomic advancements will undoubtedly augment the efficiency of Vetiver grass, particularly in the presence of elevated concentrations.

PMID:42616297 | DOI:10.1007/s10534-026-00868-w

Ecotoxicol Environ Saf. 2026 Aug 19;323:120680. doi: 10.1016/j.ecoenv.2026.120680. Online ahead of print.

ABSTRACT

Bisphenol A (BPA) is a ubiquitous environmental endocrine disruptor; its association with pancreatic cancer and its potential mechanisms of action remain unclear. This study established a comprehensive framework integrating population epidemiology, computational toxicology, machine learning, molecular dynamics simulations, and experimental validation to conduct a systematic investigation. Analysis of NHANES 2003-2016 data (N = 11,894 adults) revealed that high urinary BPA exposure (quartile 4 vs. quartiles 1-3) was significantly associated with increased cancer mortality (OR = 1.43, 95% CI: 1.04-1.96, P = 0.027; PAF = 9.51%). Intersection analysis of 597 BPA target genes and 3933 pancreatic cancer-associated genes identified 246 overlapping candidates, from which 14 core genes were prioritized through machine learning screening across 15 algorithms and 175 combinations. A diagnostic nomogram constructed based on these 14 genes achieved AUCs of 0.984 and 0.997 in the GSE15471 and TCGA-PAAD + GTEx datasets, respectively. Molecular dynamics simulations (200 ns × 3 replicates) combined with MM/GBSA binding free energy calculations indicated that the binding affinity of AHR for BPA (-57.55 ± 7.20 kcal/mol) was approximately twice that of GPRC5A (-28.87 ± 12.96) and comparable to that of known AHR ligands. Functionally, BPA exhibited a cell-type-dependent biphasic effect, inhibiting normal pancreatic ductal epithelial cell (hTERT-HPNE) viability while enhancing colony formation in AsPC-1 and MiaPaCa-2 pancreatic cancer cells, with AHR knockdown attenuating this proliferative advantage. Collectively, these findings provide population-level, computational, biophysical, and functional evidence supporting an association between BPA and pancreatic cancer, with AHR identified as a potential key molecular mediator.

PMID:42617515 | DOI:10.1016/j.ecoenv.2026.120680

Psychoneuroendocrinology. 2026 Aug 15;193:107997. doi: 10.1016/j.psyneuen.2026.107997. Online ahead of print.

ABSTRACT

OBJECTIVE: Cushing's disease (CD) is characterized by chronic exposure to excess cortisol and disruption of circadian cortisol rhythms. Given cortisol's role in affective regulation and circadian synchronization, eating disturbances-particularly those linked to mood and sleep-may represent an underexplored aspect of CD. We investigated night eating symptoms and chronotype in CD and examined their clinical, psychological, sleep-related, and endocrine correlates.

METHODS: Ninety-eight participants were included (22 active CD, 33 remission, 43 healthy controls). Night eating symptoms were assessed using the Night Eating Questionnaire (NEQ) and chronotype with the Morningness-Eveningness Questionnaire. Psychological distress and sleep were measured using Hospital Anxiety and Depression Scale, Pittsburgh Sleep Quality Index, and Insomnia Severity Index. Endocrine measures included 24-hour urinary free cortisol, late-night salivary cortisol, and 1-mg dexamethasone suppression test. Hierarchical regression models identified independent predictors of NEQ scores.

RESULTS: Patients with active CD exhibited greater night eating severity than controls (p = .005), with 16.4% meeting criteria for night eating syndrome. Chronotype did not differ across groups (p = .917). Night eating severity was not associated with cortisol biomarkers. The active disease-night eating association diminished after adjusting for psychological distress. Psychological distress and sleep disturbance independently predicted night eating, accounting for ∼59% of variance.

CONCLUSION: Night eating symptoms are elevated in active CD but appear more closely linked to psychological distress and sleep disruption than to concurrent cortisol levels. Similar chronotype across groups suggests sleep problems may occur without a shift in circadian preference. Screening for night eating may inform multidisciplinary care in CD.

PMID:42617568 | DOI:10.1016/j.psyneuen.2026.107997

Bioresour Technol. 2026 Aug 19;462:135674. doi: 10.1016/j.biortech.2026.135674. Online ahead of print.

ABSTRACT

Bisphenol A (BPA) is a widespread endocrine-disrupting contaminant in wastewater, and microbial biodegradation is a promising approach for its removal. However, BPA-degrading bacteria with clarified degradation products, reduced estrogenic activity after degradation, and demonstrated performance in real wastewater remain limited. In this study, a BPA-degrading bacterium, Sphingopyxis granuli XYQ201, was isolated from municipal wastewater and shown to utilize BPA as the sole carbon source. Strain XYQ201 completely removed 50 mg/L BPA within 38 h under laboratory conditions. Four major degradation products were identified by comparison with authentic standards, including 4-[2-hydroxy-2-(4-hydroxyphenyl)propyl]phenol, 4-[1-hydroxy-2-(4-hydroxyphenyl) propan-2-yl]phenol, 2,3-bis(4-hydroxyphenyl)propane-1,2-diol, and a previously unreported metabolite, 2,2-bis(4-hydroxyphenyl)propane-1,3-diol. Toxicological evaluation using a recombinant yeast bioreporter assay showed that the major hydroxylated metabolites had markedly lower estrogenic activity than BPA, indicating attenuation of estrogenic activity during BPA transformation. Genome analysis, quantitative PCR, and heterologous expression demonstrated that a plasmid-borne bisdAB-encoded two-component cytochrome P450 system is sufficient to initiate BPA hydroxylation and generates the mono-hydroxylated products. Public genomic and metagenomic analyses showed that putative bisdA/bisdB-like genes are phylogenetically diverse and occur in multiple natural and engineered environments. In BPA-spiked wastewater, inoculation with XYQ201 substantially enhanced BPA removal under a high-load condition. These results indicate that strain XYQ201 mediates BPA transformation through a P450-initiated hydroxylation pathway with reduced estrogenic activity of the major metabolites, and may serve as a candidate strain for bioaugmentation of BPA-contaminated wastewater.

PMID:42617814 | DOI:10.1016/j.biortech.2026.135674

Toxicol Lett. 2026 Aug 19;424:113183. doi: 10.1016/j.toxlet.2026.113183. Online ahead of print.

ABSTRACT

Bisphenol A (BPA), a widespread environmental endocrine disruptor, is associated with neurodevelopmental disorders and induces oxidative neurotoxicity. Ferroptosis, an iron-dependent cell death driven by lipid peroxidation, has been implicated in toxicant‑induced neuronal injury. However, whether BPA triggers neuronal ferroptosis through autophagy remains unclear. Using HT‑22 hippocampal neuronal cells as an in vitro model, we investigated the role of autophagy‑dependent ferroptosis in BPA neurotoxicity. BPA exposure caused oxidative damage and mitochondrial ultrastructural abnormalities. It also induced ferroptosis‑related changes, including increased malondialdehyde (MDA), prostaglandin endoperoxide synthase 2 (PTGS2) protein expression, and reactive oxygen species (ROS), as well as decreased glutathione (GSH), glutathione peroxidase 4 (GPX4), and solute carrier family 7 member 11 (SLC7A11). These effects were reversed by the ferroptosis inhibitors ferrostatin-1 (Fer-1) and deferoxamine (DFO). Pharmacological inhibition of autophagy with chloroquine (CQ) also reversed BPA-induced GPX4/SLC7A11 downregulation and PTGS2 upregulation. Notably, BPA decreased the expressions of nuclear receptor coactivator 4 (NCOA4) and ferritin heavy chain 1 (FTH1), which was blocked by CQ. Knockdown of NCOA4 attenuated BPA-induced FTH1 and GPX4 loss, and PTGS2 elevation, indicating that NCOA4-mediated ferritinophagy is required for BPA-induced ferroptosis. Mechanistically, BPA activated AMPK/ULK1 axis while inhibiting mTOR; silencing of AMPK or ULK1 partially abrogated BPA-induced autophagy and ferroptosis. Collectively, these findings demonstrate that BPA activates the AMPK/mTOR/ULK1 signaling pathway to promote NCOA4‑mediated ferritinophagy, leading to ferroptosis in HT‑22 cells. This study provides a novel insight into the molecular mechanisms underlying BPA-associated neurotoxicity.

PMID:42617960 | DOI:10.1016/j.toxlet.2026.113183