Endocrine Disruption

Anal Chim Acta. 2026 Feb 1;1385:344995. doi: 10.1016/j.aca.2025.344995. Epub 2025 Dec 9.

ABSTRACT

BACKGROUND: Endocrine disrupting compounds (EDCs) are linked to chronic conditions such as hormonal cancers, metabolic disorders, and reproductive dysfunction. They can enter drinking water through inadequate wastewater treatment and poor waste disposal, contaminating surface and groundwater. Bottled water adds risk due to leaching of packaging chemicals, especially from plastics. Since even low-level exposure may harm health, systematic monitoring is crucial. This requires advanced analytical methods able to detect and quantify multiple EDC classes at trace concentrations in bottled drinking water.

RESULTS: This study developed and validated a comprehensive multi-residue method to quantify 25 EDCs across eight chemical classes - hormones, microbial agents, mycotoxins, pesticides, pharmaceuticals, phenols, phthalates, and sunscreen agents - and to screen 983 additional suspected EDCs in drinking water. The method, based on solid-phase extraction coupled with ultrahigh performance liquid chromatography-high resolution mass spectrometry, was optimized using factorial design to ensure accuracy and reliability. Validation with still water demonstrated excellent linearity (R² ≥ 0.99), low detection limits (0.5-5.0 ng L^-1), and compliance with international criteria for recovery, precision, and measurement uncertainty. Cross-validation on sparkling water further confirmed robustness, with only 17β-estradiol showing slightly elevated recovery at the lowest concentration. Stability tests showed analytes remained intact for 72 h under dark conditions. Application to 37 Belgian bottled waters revealed 17 EDCs, with bisphenol B and acetaminophen most abundant. More compounds occurred in plastic than glass bottles, while mineral water showed higher α-zearalanol than spring water. Notably, premium plastic bottled water contained increased phthalate levels.

SIGNIFICANCE: This study presents a robust method for multi-class EDC analysis in bottled drinking water, offering high sensitivity and broad coverage, including EU watch list substances. Using an extensive suspect screening database from international inventories, it is the first Belgian study to map diverse EDCs in popular bottled water brands. The findings provide crucial data for public health risk assessment and inform regulatory and commercial decisions, emphasizing packaging, source type, and retail price as key factors.

PMID:41526113 | DOI:10.1016/j.aca.2025.344995

Pathology. 2025 Nov 20:S0031-3025(25)00341-1. doi: 10.1016/j.pathol.2025.10.005. Online ahead of print.

ABSTRACT

Anaemia and bone disease commonly co-exist, particularly in chronic conditions such as haemoglobinopathies and chronic kidney disease. The effects on bone are mediated by multiple factors, including marrow expansion, iron overload, endocrine dysfunction, and disruptions in mineral metabolism. These changes compromise bone strength, increasing the risk of osteoporosis and fractures. Although therapeutic advances such as iron infusion and chelation therapy have significantly improved the management of anaemia and patient outcomes, their effects on bone health are often under-recognised with osteoporosis detection occurring after a fracture. Furthermore, with denosumab being a popular anti-resorptive choice amongst clinicians, an emerging and under-appreciated complication is the increasing number of case reports describing hypophosphataemia associated with concurrent anti-resorptive and parenteral iron. This review discusses the bi-directional relationship between anaemia and bone metabolism. By focusing on the central role of fibroblast growth factor-23 (FGF-23), as a link between anaemia, phosphate regulation, and bone metabolism, this review draws attention to under-recognised skeletal risks. Importantly, it offers practical recommendations for monitoring, bridging mechanistic insights with clinical practice where current guidelines remain limited.

PMID:41526204 | DOI:10.1016/j.pathol.2025.10.005

Environ Geochem Health. 2026 Jan 13;48(2):98. doi: 10.1007/s10653-025-02971-2.

ABSTRACT

Microplastics (MPs) ubiquitously contaminate ecosystems and serve as efficient vectors for heavy metals (HMs), amplifying their environmental mobility and bioavailability. Although the individual toxicological impacts of MPs and HMs are well-documented, their combined effects, driven by complex adsorption dynamics and synergistic toxicity, remain poorly understood. This review systematically synthesizes recent advances in MP-HM interactions, with a focus on adsorption mechanisms such as electrostatic attraction, biofilm facilitation, and co-precipitation. Key factors governing adsorption efficiency, including polymer crystallinity, environmental aging, biofilm formation, and water chemistry, are critically examined. Furthermore, we elucidate the compounded toxicity of MP-HM complexes across aquatic and terrestrial organisms, manifesting as oxidative stress, multi-organ damage, and endocrine disruption, with bioaccumulation risks that propagate through food chains to humans. By identifying critical knowledge gaps, particularly regarding long-term ecotoxicological outcomes and transgenerational effects, this review provides a mechanistic framework to guide future research and evidence-based policy for mitigating composite pollution in a rapidly changing environment.

PMID:41526583 | DOI:10.1007/s10653-025-02971-2

BMC Endocr Disord. 2026 Jan 12. doi: 10.1186/s12902-026-02166-5. Online ahead of print.

ABSTRACT

BACKGROUND: Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder influenced by genetic, hormonal, and environmental factors. In the environmental context, phthalate esters, specifically Mono-2-ethylhexyl phthalate (MEHP) and Di-2-ethylhexyl phthalate (DEHP), have emerged as potential endocrine disruptors, demanding a mysterious role in PCOS.

OBJECTIVE: The study aimed to compare demographic, biochemical parameters, and levels of phthalate esters, specifically MEHP and DEHP, in women with and without PCOS. The association between these phthalate esters and different biochemical markers was also of interest for investigation.

METHODS: The study included 160 participants, 90 in the PCOS group and 70 in the control group. Demographic and biochemical parameters were measured and compared for both groups. The levels of MEHP and DEHP in serum were determined using High-Performance Liquid Chromatography (HPLC).

RESULTS: The PCOS group had a significantly higher average age and Body Mass Index (BMI) compared to the control group (p < 0.0001). Testosterone and luteinizing hormone (LH) levels were significantly elevated in the PCOS group (p < 0.05). In contrast, estradiol, follicle-stimulating hormone (FSH), prolactin, LH/FSH ratio, dehydroepiandrosterone sulfate, and thyroid-stimulating hormone (TSH) levels showed no significant difference. Notably, MEHP and DEHP levels were significantly higher in the PCOS group compared to the control group (47.33 ± 27.67 vs. 31.09 ± 18.74, p < 0.0001 and 31.03 ± 25.76 vs. 22.98 ± 19.65, p = 0.03 respectively). DEHP levels in the PCOS group demonstrated significant positive correlations with LH levels, LH/FSH ratio, and estradiol levels. In contrast, MEHP levels showed no significant correlations with the evaluated biochemical parameters. Neither MEHP nor DEHP displayed significant correlations with any examined parameters in the control group.

CONCLUSION: This study underscores the elevated levels of MEHP and DEHP in women with PCOS, highlighting the potential influence of these environmental toxins in PCOS pathogenesis.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:41526914 | DOI:10.1186/s12902-026-02166-5

Environ Geochem Health. 2026 Jan 13;48(2):98. doi: 10.1007/s10653-025-02971-2.

ABSTRACT

Microplastics (MPs) ubiquitously contaminate ecosystems and serve as efficient vectors for heavy metals (HMs), amplifying their environmental mobility and bioavailability. Although the individual toxicological impacts of MPs and HMs are well-documented, their combined effects, driven by complex adsorption dynamics and synergistic toxicity, remain poorly understood. This review systematically synthesizes recent advances in MP-HM interactions, with a focus on adsorption mechanisms such as electrostatic attraction, biofilm facilitation, and co-precipitation. Key factors governing adsorption efficiency, including polymer crystallinity, environmental aging, biofilm formation, and water chemistry, are critically examined. Furthermore, we elucidate the compounded toxicity of MP-HM complexes across aquatic and terrestrial organisms, manifesting as oxidative stress, multi-organ damage, and endocrine disruption, with bioaccumulation risks that propagate through food chains to humans. By identifying critical knowledge gaps, particularly regarding long-term ecotoxicological outcomes and transgenerational effects, this review provides a mechanistic framework to guide future research and evidence-based policy for mitigating composite pollution in a rapidly changing environment.

PMID:41526583 | DOI:10.1007/s10653-025-02971-2

Food Sci Biotechnol. 2025 Nov 4;35(1):285-296. doi: 10.1007/s10068-025-02019-2. eCollection 2026 Jan.

ABSTRACT

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in reproductive-aged women, characterized by disrupted ovarian function due to multiple factors. Angelica gigas Nakai (AG), known for its multi-compound and multi-target properties, was investigated as a potential therapy using an integrated approach combining network pharmacology and experimental validation. Active compounds of AG were matched with PCOS-related genes, and 45 overlapping targets were identified. Network analysis highlighted INS, LEP, and IGF1 as key nodes. KEGG enrichment indicated involvement of the AMPK signaling pathway. In vivo, estradiol valerate-induced PCOS rats treated with AG (1 mg/kg) displayed restored estrous cycles, normalized ovarian weight, reduced serum testosterone, and improved follicular maturation. Consistently, AG upregulated AMPK expression while downregulating INS, IGF1, Leptin, and PPAR-γ. These findings suggest that AG may serve as a promising therapeutic candidate for PCOS.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-025-02019-2.

PMID:41523694 | PMC:PMC12789357 | DOI:10.1007/s10068-025-02019-2

Nutr Rev. 2026 Jan 12:nuaf272. doi: 10.1093/nutrit/nuaf272. Online ahead of print.

ABSTRACT

CONTEXT: Bisphenol A (BPA) is a chemical found in polycarbonate plastics that can disrupt the endocrine system of humans and animals. Because human exposure to BPA is ubiquitous, due to its high-volume production and use, research into methods of mitigating its toxicity is considered imperative.

OBJECTIVE: The objective of this study thus was to summarize current knowledge of the effects of probiotics on BPA toxicity and of methods of restoring the overall health of organisms exposed to it.

DATA SOURCES: An electronic search of the literature was undertaken using the PubMed, The Cochrane Library, Scopus, and Web of Science databases to identify all relevant articles. Gray literature was also screened. The search process ended on March 31, 2025.

DATA EXTRACTION: The following data were extracted from each intervention study: type of animal model, number of animals, BPA exposure, daily dose and type of probiotic supplementation, placebo, and other treatment intervention. The following details for experimental animals was also recorded: health status, mean age, main outcomes (changes in BPA toxicity; BPA content in stool, blood, saliva, or urine; decreased oxidative stress and endocrine disruption; changes in metabolic parameters such as insulin, lipid profile, and liver parameters).

DATA ANALYSIS: A total of 404 studies were identified using the databases. Five in vivo and 7 in vitro articles met the inclusion criteria and were included in the final analysis. Probiotic bacteria, especially Lactobacillus plantarum, Bacillus subtilis, L. acidophilus, Lactococcus lactis, and Lactobacillus reuteri have potential applications in the bioremediation of BPA.

CONCLUSION: This review provides information on whether probiotics may play a role in effectively relieving the outcomes of BPA exposure; therefore, the aim was achieved. The findings provide valuable insights for the development of intervention strategies and could have practical applications in food formulation and probiotic supplementation.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration No. CRD42023470061.

PMID:41524726 | DOI:10.1093/nutrit/nuaf272

Growth Horm IGF Res. 2026 Jan 7;83:101679. doi: 10.1016/j.ghir.2026.101679. Online ahead of print.

ABSTRACT

The growth plate (physis) is a highly specialized cartilaginous organ that drives longitudinal bone growth and ultimately determines adult stature. Its zonal architecture, including the resting, proliferative, hypertrophic, and calcification zones, integrates stem-like progenitor activity, clonal chondrocyte expansion, matrix remodeling, vascular invasion, and replacement by bone. Here, we review how the structural organization of the growth plate emerges from the interplay among extracellular matrix composition, sulfation pathways, and canonical paracrine signaling pathways, including Ihh-PTHrP, BMP, Wnt, and FGF. We highlight advances in our understanding of chondrocyte fate, including lineage-tracing studies demonstrating that resting-zone PTHrP⁺ cells function as skeletal stem cells and that hypertrophic chondrocytes can transdifferentiate into osteoblasts or dedifferentiate into progenitors rather than undergoing obligatory apoptosis. We also summarize how endocrine axes, including the GH/IGF-1, thyroid hormone, sex steroids, glucocorticoids, and vitamin D, coordinate the tempo of growth, the dynamics of growth plate senescence, and the timing of epiphyseal fusion, with emphasis on species differences between rodents and humans. Finally, we use monogenic skeletal dysplasias, endocrine disorders, and acquired conditions such as rickets and slipped capital femoral epiphysis as "experiments of nature" that illuminate how specific molecular perturbations disrupt growth plate physiology. Together, these converging lines of evidence reframe the growth plate as a dynamic stem-cell and progenitor niche whose fate is plastic, highly regulated, and increasingly targetable for therapy in disorders of linear growth.

PMID:41520458 | DOI:10.1016/j.ghir.2026.101679

Ecotoxicol Environ Saf. 2026 Jan 10;309:119698. doi: 10.1016/j.ecoenv.2026.119698. Online ahead of print.

ABSTRACT

Based on toxicological evidence, human exposure to phthalates (PHs) and diisononylcyclohexane-1,2-dicarboxylate (DINCH) may contribute to adverse health effects, especially during vulnerable developmental stages. To support the exposure assessment for this group of endocrine disruptors, we developed and validated a method for the analysis of 14 PH and 3 DINCH metabolites in human urine and maternal milk, applied the method in a pilot study, and identified crucial obstacles in the path of establishing maternal milk as a routine matrix in human biomonitoring. Urine and milk samples were extracted with solid-phase extraction (SPE) and QuEChERS salts, respectively, and analysed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The method accuracy was confirmed for urine samples via a certified standard reference material and the G-EQUAS intercomparison programme. We identified a need for sampling protocols, reference materials, and external method verification schemes in order to establish maternal milk as a routine matrix. Finally, the method was tested for its applicability in a pilot biomonitoring study on 30 paired urine and milk samples from lactating mothers, with medians ranging from <LLOQ - 15 µg/L in urine and <LLOQ - 16 µg/L in maternal milk and generally higher detection rates in urine. Furthermore, the results indicate extensive monoester formation under cooled storage conditions, resulting in potentially high infantile exposure to phthalate monoesters for which, to date, no guidance values exist despite their demonstrated toxicity.

PMID:41520534 | DOI:10.1016/j.ecoenv.2026.119698

Reprod Biomed Online. 2025 Aug 30;52(3):105236. doi: 10.1016/j.rbmo.2025.105236. Online ahead of print.

ABSTRACT

RESEARCH QUESTION: Does maternal occupational exposure to endocrine-disrupting chemicals (EDC) during pregnancy affect reproductive hormone concentrations in adult sons?

DESIGN: Data from a cross-sectional study of 2326 Swiss conscripts collected between 2005 and 2017 were analysed. On inclusion, the conscripts' mothers completed a detailed questionnaire about their pregnancy. A job-exposure matrix was used to assess exposure to 10 categories of potential EDC. Reproductive hormones - FSH, LH, total and free testosterone, oestradiol and sex hormone-binding globulin (SHBG) - were determined in serum samples from all conscripts whose mothers were exposed to EDC during pregnancy (n = 138) and a random sample of non-exposed conscripts (n = 276). Multiple linear regression analyses were adjusted for potential confounders.

RESULTS: Prenatal exposure to phthalates or alkyl phenolic compounds was significantly associated with higher FSH concentrations (aβ = 0.26, 95% CI 0.03-0.49, and aβ = 0.22, 95% CI 0.02-0.42, respectively) and prenatal exposure to pesticides was significantly associated with higher SHBG concentrations (aβ = 0.22, 95% CI 0.05-0.38). No statistically significant associations were found between other EDC categories and reproductive hormones.

CONCLUSIONS: Maternal occupational exposure to certain types of EDC during pregnancy was associated with the concentrations of reproductive hormones in adult sons. These findings require replication in larger, prospective population studies.

PMID:41520584 | DOI:10.1016/j.rbmo.2025.105236

Nutrients. 2026 Jan 1;18(1):142. doi: 10.3390/nu18010142.

ABSTRACT

Endometriosis is a chronic, oestrogen-dependent inflammatory condition affecting approximately 10% of women of reproductive age, frequently associated with chronic pelvic pain, dysmenorrhoea and infertility, substantially impairing quality of life. While pharmacological and surgical therapies represent the standard of care, growing evidence indicates that lifestyle and dietary factors play an important complementary role in symptom management and may influence disease progression. Regular physical activity appears to attenuate systemic inflammation, improve hormonal regulation and support psychological well-being. Dietary patterns rich in anti-inflammatory components, particularly Mediterranean-diets and low-inflammatory diets, have been associated with reduced pain and improved gastrointestinal symptoms, whereas high consumption of red and processed meats may increase disease risk. Micronutrients and selected supplements, including vitamins C, E and D, magnesium, zinc, folate, omega-3 fatty acids, N-acetylcysteine, curcumin, probiotics and green tea polyphenols, show promising but variable evidence for symptom relief. Additional lifestyle factors, such as avoiding endocrine-disrupting chemicals, moderating alcohol intake, ensuring adequate sleep and managing psychological stress, may further modulate inflammatory and hormonal pathways relevant to the disorder. Overall, current evidence indicates that integrating lifestyle interventions alongside conventional treatments offers clinically relevant benefits, although larger, well-designed clinical studies are needed to clarify the magnitude of these effects and to explore further promising lifestyle-based therapeutic approaches.

PMID:41515258 | PMC:PMC12787854 | DOI:10.3390/nu18010142

Int J Mol Sci. 2025 Dec 19;27(1):39. doi: 10.3390/ijms27010039.

ABSTRACT

Endocrine-disruptive chemicals (EDCs) are human-made substances that mimic the action of endocrine hormones and can lead to adverse health effects in living organisms, including humans [...].

PMID:41515922 | PMC:PMC12786094 | DOI:10.3390/ijms27010039

Int J Mol Sci. 2025 Dec 21;27(1):90. doi: 10.3390/ijms27010090.

ABSTRACT

Carbofuran, a widely used carbamate pesticide, is an endocrine disruptor with documented reproductive toxicity, yet the mechanisms underlying its ovarian toxicity remain incompletely understood. This study employed integrated network toxicology and untargeted metabolomics to investigate these mechanisms in female C57BL/6J mice that had been chronically exposed to carbofuran (0.5 or 2.0 mg/kg for 45 days, once daily). Methods included histopathological evaluation, serum hormone ELISA, network prediction of toxicity targets, molecular docking, and metabolomics profiling. Results demonstrated that carbofuran exposure induced dose-dependent ovarian damage, including reduced follicular reserve, increased atresia, abnormal corpus luteum, and disrupted hormone levels. Network toxicology identified 38 common targets, with EGFR, GSK3B, APP, and JAK2 as core proteins, indicating potential high affinity. Metabolomics suggests significant alterations in pathways such as phenylalanine, tyrosine, tryptophan biosynthesis and arginine/proline metabolism. Our collective evidence indicates that carbofuran may induce ovarian toxicity through multifaceted mechanisms involving endocrine disruption, oxidative stress, inflammatory activation, and metabolic disturbance. This study provides novel experimental insights into the reproductive toxicity mechanisms of carbofuran, offering a theoretical basis for health risk assessment and intervention strategies.

PMID:41515972 | PMC:PMC12786280 | DOI:10.3390/ijms27010090

Int J Mol Sci. 2025 Dec 29;27(1):369. doi: 10.3390/ijms27010369.

ABSTRACT

The intestinal microbiota, a diverse community of microorganisms residing in the human gut, recently attracted considerable attention as a contributing factor to various neurological disorders, including Alzheimer's Disease (AD). Within the established framework of the gut-brain axis (GBA) concept, it is commonly suggested that dysbiosis, through microbial metabolites entering the brain, affect the cognitive functions in patients with AD. However, evidence for such a role of dysbiosis remains largely associative, and the complexity of the communication channels between the gut and the brain is not fully understood. Moreover, the new players of the GBA are emerging and the AD concept is constantly evolving. The objective of this narrative review is to synthesize the current evidence on the humoral, endocrine, immune, and neural communication mechanisms linking the gut and brain in AD and highlight newly discovered GBA messengers such as microRNAs, extracellular vesicles, T-cells, and the intestinal hormones, including emerging neuroprotective role for glucagon-like peptide-1 (GLP-1). Based on this knowledge, we aimed to develop a conceptual understanding of the GBA function in health and AD. We specify that, in AD, the GBA goes beyond a disrupted microbiome, but operates in conjunction with impaired intestinal secretion, motility, barrier permeability, and neuroinflammatory signaling. These factors are associated with the dysfunction of the hypothalamic-pituitary axis, altered somatic and autonomic neuronal gut regulation, and abnormal, due to memory problems, behavioral aspects of food intake. Identifying the individual profile of key molecular and cellular players contributing to an unbalanced GBA should optimize existing approaches or propose new approaches for the complex therapy of AD.

PMID:41516244 | PMC:PMC12785541 | DOI:10.3390/ijms27010369

Animals (Basel). 2025 Dec 29;16(1):94. doi: 10.3390/ani16010094.

ABSTRACT

Pollution in aquatic ecosystems is intensifying under the combined pressures of climate change and anthropogenic contaminants, with nanoplastics (NPs) emerging as a critical threat to fish reproduction. Although extensive research has demonstrated the physiological impacts of NPs, their direct effects on sperm quality and functionality remain poorly characterized. This review synthesizes evidence from original research articles that specifically examined NPs' impacts on fish sperm quality and related reproductive endpoints. The findings reveal that NPs consistently impair sperm motility, viability, and fertilization capacity, while inducing oxidative stress, DNA damage, mitochondrial dysfunction, and endocrine disruption. Particle size, surface chemistry, and exposure route were identified as key determinants of toxicity, with direct sperm exposure causing immediate impairments and chronic or maternal transfer exposures leading to systemic and transgenerational effects. Notably, several studies reported reduced offspring survival, altered development, and disrupted gene expression, highlighting the intergenerational risks of NPs contamination. Despite these advances, significant knowledge gaps remain, including limited research on marine wild and cultured fish species, the effects of diverse life histories on NPs toxicity, environmentally relevant exposure levels, and the combined effects of NPs with other stressors. Overall, this review underscores that fish sperm are highly sensitive to NPs pollution, with consequences that extend across generations and threaten population stability, calling for urgent mechanistic and ecologically realistic investigations.

PMID:41514781 | PMC:PMC12784842 | DOI:10.3390/ani16010094

Int J Mol Sci. 2025 Dec 30;27(1):399. doi: 10.3390/ijms27010399.

ABSTRACT

Microplastics and nanoplastics (<5 mm and <1 μm, respectively) are emerging contaminants now ubiquitous across environmental matrices and increasingly recognized for their impacts on human health. These particles commonly adsorb or contain endocrine-disrupting chemicals-such as bisphenol-A and phthalate additives-that together trigger complex biological responses. This review examines the central role of oxidative stress in mediating the toxicity of microplastics and associated endocrine disruptors across multiple organ systems. We discuss mechanisms including cellular uptake, reactive oxygen species generation, mitochondrial dysfunction, impairment of antioxidant defenses, and activation of key signaling pathways. Organ-specific effects on reproductive health, cardiovascular function, hepatic metabolism, gut barrier integrity, and neurological systems are highlighted. Current evidence strongly supports oxidative stress as a pivotal mechanism linking microplastic exposure to systemic toxicity, underscoring important implications for public health policy and clinical intervention strategies.

PMID:41516273 | PMC:PMC12785609 | DOI:10.3390/ijms27010399

J Hazard Mater. 2026 Jan 6;503:141069. doi: 10.1016/j.jhazmat.2026.141069. Online ahead of print.

ABSTRACT

The widespread use of pesticides has raised serious concerns about their combined impact on aquatic life; however, the underlying mechanisms of reproductive toxicity remain poorly defined. Adult Japanese medaka (Oryzias latipes) were exposed for 60 days to fenvalerate (FEN, 0.039 mg/L), tebuconazole (TEB, 1.0 mg/L), or their combination (FEN + TEB, 0.01 mg/L + 0.5 mg/L) to evaluate single and mixture-induced disruption of the hypothalamic-pituitary-gonadal (HPG) axis. Long-term exposure to either FEN or TEB significantly reduced fertilization, hatchability, and survival rates, with the combined exposure group exhibiting the most severe adverse effects. Gonadal histological assessment revealed severe degenerative alterations, disrupted spermatogenesis, and reduction of germ cells, follicular atresia, and loss of structural integrity. Transcriptional profiling further demonstrated broad disturbances across the HPG axis, with significant downregulation of cyp19a1, dmrt1, fshr, gnrh1, gnrh2, lhβ, and star, alongside altered transcription of erα, erβ, fshβ, vtg1, and vtg2 in a sex-dependent pattern. The observed impairment of gametogenesis is likely attributable to dysregulated transcriptional control, as molecular docking revealed stable binding of FEN and TEB to Dmrt1 and aromatase (Cyp19a1). In addition, biochemical assays confirmed that co-exposure to FEN and TEB also led to oxidative stress and immune suppression, reflected by reductions in CAT, GSH-PX, LZM, and SOD activities and elevated MDA levels. These findings provide integrated molecular and histopathological evidence that FEN and TEB synergistically disrupt endocrine signaling, trigger oxidative imbalance, and impair gonadal integrity in fish, highlighting the ecological risks associated with pesticide mixtures in aquatic environments.

PMID:41518803 | DOI:10.1016/j.jhazmat.2026.141069

Ecotoxicol Environ Saf. 2026 Jan 9;309:119713. doi: 10.1016/j.ecoenv.2026.119713. Online ahead of print.

ABSTRACT

The co-occurrence of pesticides and heavy metals in aquatic ecosystem poses a significant threat to biota, yet the interactive toxicological effects and mechanisms remain poorly understood, especially during their early developmental stages. In this study, we employed zebrafish embryos as a sensitive model to investigate the combined effects of fungicide triadimefon (TDF) and copper (Cu^{2 +}) on endocrine regulation via the hypothalamus-pituitary-thyroid (HPT) and hypothalamus-pituitary-gonadal (HPG) axes. Our results showed that both individual and combined exposures to TDF and Cu²⁺ significantly increased the mortality and malformation rates, impaired swimming ability, and exhibited dose-dependent toxicity. Compared to Cu²⁺ exposure alone, TDF exposure significantly reduced thyroxine (T4) levels in zebrafish, and the co-exposure further exacerbated this reduction. Cu²⁺ alone downregulated several HPT-related genes (e.g., TTR), whereas TDF exposure and co-exposure upregulated TTR expression. Regarding reproductive toxicity, Cu²⁺ exhibited a stronger inhibitory effect on key HPG genes (e.g., cyp19a) compared to TDF; however, co-exposure significantly enhanced these inhibitory and induced the upregulation of genes such as StAR. The results of this study provide insights into the dual disruption of thyroid and reproductive endocrine functions by TDF and Cu²⁺, improveing our understanding of the combined ecological risks posed by pesticide and heavy metal co-contamination.

PMID:41518983 | DOI:10.1016/j.ecoenv.2026.119713

J Nutr Biochem. 2026 Jan 8:110262. doi: 10.1016/j.jnutbio.2026.110262. Online ahead of print.

ABSTRACT

Zinc (Zn) deficiency disrupts redox homeostasis in the body. The pancreas is a vital digestive and endocrine organ of the body, and its normal functional operation cannot proceed without the involvement of Zn. In this study, we established in vivo mouse models, including the normal Zn group (CG, 34 mg Zn/kg), Zn-deficient group (LZn, 2 mg Zn/kg), and Zn-supplemented group (HZn, 100 mg Zn/kg), as well as an in vitro Zn-deficient model of Mouse INsulinoma 6 (MIN6) cells. We systematically investigated the effects of Zn deficiency on pancreatic oxidative stress, inflammation, and cell death. The results showed that Zn deficiency significantly decreased the activities of α-amylase and lipase in the pancreas, and led to pancreatic histological damage. Through flow cytometry and detection of antioxidant enzyme activities, it was found that Zn deficiency induces excessive accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA) in the pancreas, and inhibits antioxidant enzyme activities. Using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot, it was observed that Zn deficiency activates the TLR4/NF-κB pathway and significantly increases the expression of the NLRP3 inflammasome and inflammatory factors. Furthermore, Zn deficiency significantly upregulates the expression of apoptosis-related factors (Bax, Caspase-3, Caspase-7, Caspase-9) and necroptosis-related factors (RIPK1, RIPK3, MLKL). Treatment with the antioxidant N-acetylcysteine (NAC) reduces the level of ROS and inhibits the activation of the TLR4/NF-κB pathway, thereby alleviating Zn deficiency-induced inflammation and cell death. Taken together, Zn deficiency induces pancreatic inflammation and cell death by regulating the ROS/TLR4/NF-κB pathway.

PMID:41519441 | DOI:10.1016/j.jnutbio.2026.110262

Mutat Res Genet Toxicol Environ Mutagen. 2026 Jan;909:503913. doi: 10.1016/j.mrgentox.2025.503913. Epub 2025 Dec 17.

ABSTRACT

Bis(2-ethylhexyl) phthalate (DEHP) is a widely used synthetic compound known for its significant environmental and health hazards. It is particularly recognized for disrupting cellular functions by interfering with endocrine activity and inducing oxidative stress. Our previous research established that DEHP causes both cytotoxic and genotoxic effects in third instar larvae of Drosophila melanogaster (hsp70-lacZ) Bg⁹. The present study explores the protective role of apigenin, a naturally occurring flavonoid, against DEHP-induced toxicity in the model organism. Apigenin was mixed into the larval diet at concentrations of 20, 40, 60, and 80 µM, alongside 0.02 M DEHP, and administered for 24 h. Our findings revealed that apigenin supplementation significantly reduced gut tissue damage, lowered Hsp70 expression, and decreased both the apoptotic index and DNA damage in third instar larvae exposed to DEHP. Apigenin effectively reduced the elevated activities of caspase-3 and caspase-9 induced by Bis(2-ethylhexyl) phthalate exposure. These results highlight apigenin's potential as an effective protective agent against the toxic effects of DEHP.

PMID:41519511 | DOI:10.1016/j.mrgentox.2025.503913

Int J Mol Sci. 2025 Dec 30;27(1):399. doi: 10.3390/ijms27010399.

ABSTRACT

Microplastics and nanoplastics (<5 mm and <1 μm, respectively) are emerging contaminants now ubiquitous across environmental matrices and increasingly recognized for their impacts on human health. These particles commonly adsorb or contain endocrine-disrupting chemicals-such as bisphenol-A and phthalate additives-that together trigger complex biological responses. This review examines the central role of oxidative stress in mediating the toxicity of microplastics and associated endocrine disruptors across multiple organ systems. We discuss mechanisms including cellular uptake, reactive oxygen species generation, mitochondrial dysfunction, impairment of antioxidant defenses, and activation of key signaling pathways. Organ-specific effects on reproductive health, cardiovascular function, hepatic metabolism, gut barrier integrity, and neurological systems are highlighted. Current evidence strongly supports oxidative stress as a pivotal mechanism linking microplastic exposure to systemic toxicity, underscoring important implications for public health policy and clinical intervention strategies.

PMID:41516273 | PMC:PMC12785609 | DOI:10.3390/ijms27010399

Toxicol Lett. 2026 Jan 7;416:111826. doi: 10.1016/j.toxlet.2026.111826. Online ahead of print.

ABSTRACT

This study examined the hepatic effects of parous exposure to the rubber-derived contaminant N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and its oxidation product, N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPDQ), in C57BL/6 mice during gestation and lactation. Both compounds exhibited dose-dependent bioaccumulation in the liver of the F0 generation and lactated F1 offspring, with 6PPDQ accumulating more due to its greater stability. Lactational transmission of both compounds was observed, and the accumulation declined with age, disappearing by 8 weeks. Notably, 6PPDQ exposure resulted in reduced body weight in mature F1 female mice, which was associated with altered cholesterol metabolism and disrupted expression of the estrogen receptor gene. In these mice, molecular analysis revealed dysregulation of key cholesterol-related genes, such as HMGCR and PCSK9. In contrast, male offspring showed less pronounced effects. These results indicate that the toxicity of 6PPD and 6PPDQ can be transmitted through placental and lactational pathways, with 6PPDQ presenting a greater risk, particularly to female mice, through its impact on cholesterol metabolism and endocrine signalling. These findings offer valuable insights for assessing the environmental and health risks associated with these compounds.

PMID:41513114 | DOI:10.1016/j.toxlet.2026.111826

Cancer Epidemiol Biomarkers Prev. 2026 Jan 9;35(1):7-9. doi: 10.1158/1055-9965.EPI-25-1629.

ABSTRACT

Emerging research suggests that environmental contaminants may influence the risk of breast cancer, particularly through exposure to endocrine disruptors and carcinogens present in the air, water, and consumer products. In a recent study, Borowsky and colleagues conducted a case-case study in Florida and identified a higher likelihood of triple-negative breast cancer among women living less than 4 miles of superfund sites compared with those with other breast cancer subtypes. In addition, Borowsky and colleagues observed a higher likelihood of triple-negative breast cancer among women residing in areas with high levels of particulate matter with aerodynamic diameter <2.5 µm (PM2.5) versus other subtypes. Careful consideration when interpreting these findings is needed due to limitations in study design, including temporal misalignment in assigning exposures, conceptual disconnect between PM2.5 and toxic exposures at superfund sites, selection bias, and the absence of information on specific breast cancer subtypes as well as reproductive and hormonal factors. We suggest areas for clarification and future research. Notably, the study raises important hypotheses about the impact of environmental contaminants on the risk of distinct breast cancer subtypes. This is particularly important for populations that experience higher levels of environmental exposures because of structural and social drivers of health. See related article by Borowsky et al., p. 59.

PMID:41508843 | DOI:10.1158/1055-9965.EPI-25-1629

Aquat Toxicol. 2025 Dec 24;291:107692. doi: 10.1016/j.aquatox.2025.107692. Online ahead of print.

ABSTRACT

New pollutants impair the reproduction and development of offspring in marine fish after parental exposure. While florfenicol has been frequently detected in the environment and organisms, limited information is available on its effects on the endocrine system of marine fishes and their developmental defects in offspring. In this study, six-month-old marine medaka (Oryzias melastigma) were exposed to florfenicol at 0.1 and 89 μg/L (measured) for 28 days. A cross-mating experimental design was employed to generate offspring embryos from various cross-mates by combining and mating control and exposed O. melastigma (male or female), thereby differentiating maternal and paternal influences. The results showed that either paternal or maternal exposure to florfenicol could affect the embryonic development of offspring. Additionally, parental exposure to florfenicol resulted in lower hatching rates and increased mortality in F1 embryos, even when cultured in clean seawater. Furthermore, the embryos of each cross-breeding group displayed distinct expressions of apoptosis-related genes, indicating that florfenicol can induce varying degrees of apoptosis in embryos. Altered expressions of genes related to endocrine disruption in the gonads were also identified, and morphological changes were observed in ovarian and testicular tissue sections of adult fish. The florfenicol-treated group showed a decrease in mature oocytes in the ovaries and an increase in interstitial tissue in the tests. In general, chronic exposure to florfenicol caused energy metabolism disorders, altered the expression of endocrine disruption related genes, damaged gonadal tissues, and led to reproductive dysfunction in O. melastigma, thereby impairing the production and development of their offspring. Overall, the key findings of this study demonstrated that extended exposure of paternal or maternal exposure to florfenicol significantly induced reproductive toxicity in adult medaka, leading to developmental toxicity in their offspring.

PMID:41512407 | DOI:10.1016/j.aquatox.2025.107692

Transl Cancer Res. 2025 Dec 31;14(12):8655-8666. doi: 10.21037/tcr-2025-1785. Epub 2025 Dec 24.

ABSTRACT

BACKGROUND: Perchlorate is a persistent environmental contaminant and endocrine disruptor that inhibits iodine uptake through the sodium iodide symporter. While its thyroid toxicity is well recognized, evidence regarding its association with malignancies of endocrine-related tissues is limited. This study aimed to investigate the relationship between urinary perchlorate and the occurrence of thyroid cancer and pancreatic cancer in a nationally representative U.S. adult population.

METHODS: Data from 20,316 adults in the National Health and Nutrition Examination Survey (NHANES; 2003 to 2018) were analyzed. Urinary perchlorate was measured using ion chromatography with electrospray tandem mass spectrometry. Urinary perchlorate levels were creatinine-corrected before analysis. Weighted multivariable logistic regression was applied to assess associations with self-reported physician-diagnosed thyroid cancer and pancreatic cancer. Bayesian correlation analysis was performed for pancreatic cancer and thyroid cancer due to the small number of cases. Restricted cubic spline models were used to explore dose-response relationships.

RESULTS: The normalized urinary perchlorate level was significantly associated with both thyroid (P=0.041) and pancreatic cancer (P<0.001). This association remained significant across models when analyzed by quartiles [thyroid cancer: odds ratio (OR) =3.81, 95% confidence interval (CI): 1.26-11.5, P=0.02; pancreatic cancer: OR =13.4, 95% CI: 1.13-159, P=0.04]. Bayesian analysis provided robust evidence supporting these associations (Bayes factor: thyroid cancer =139.525; pancreatic cancer =176.853). No clear dose-response relationship was observed for either cancer type.

CONCLUSIONS: Perchlorate exposure was associated with both thyroid and pancreatic cancers. This study provides evidence supporting its potential role in endocrine-related carcinogenesis and underscores the need for further research and exposure-reduction strategies.

PMID:41510099 | PMC:PMC12776155 | DOI:10.21037/tcr-2025-1785

Aquat Toxicol. 2025 Dec 29;291:107701. doi: 10.1016/j.aquatox.2025.107701. Online ahead of print.

ABSTRACT

Bisphenol S (BPS) is a widely used synthetic compound and is known as an endocrine-disrupting chemical (EDC). The ability of BPS to bind predominantly to estrogen receptors raises significant concern, as it can interfere with different neurological functions, leading to neurobehavioural deficits. Despite extensive research documenting various adverse effects of BPS in adult fish, its neurobehavioural effects, especially in early life stages of fish, remain poorly understood. In the present study, zebrafish embryos (4-hours post fertilization, hpf) were exposed to an environmentally relevant concentration of BPS (30 μg/L), in addition to control and DMSO (0.01%; vehicle control), until 120 hpf, followed by behavioural, biochemical, and molecular assessments. BPS exposure impaired tail coiling frequency in embryos (20 hpf), and thigmotaxis and reflexive movement behaviour (120 hpf) in zebrafish larvae. At 120 hpf, larvae showed elevated reactive oxygen species (ROS), increased apoptosis, and higher malondialdehyde (MDA) levels, indicating lipid peroxidation and oxidative damage. Biochemical analysis further demonstrated that BPS significantly increased whole body serotonin (5-HT) and acetylcholine levels at 120 hpf. Moreover, gene expression analysis at 120 hpf indicated that BPS exposure resulted in the dysregulation of genes involved in dopaminergic, serotonergic and cholinergic neurotransmitter pathways, apoptosis pathway, oxidative stress response, and neuroinflammation. These findings suggest that BPS induces oxidative stress, neuroinflammation and apoptosis, leading to the disruption of neural development and signaling pathways involved in regulating behavioural responses. Overall, our study provides new insights into the behavioural effects and underlying neurotoxic mechanisms of developmental BPS exposure in larval zebrafish.

PMID:41512408 | DOI:10.1016/j.aquatox.2025.107701

J Hazard Mater. 2026 Jan 7;503:141086. doi: 10.1016/j.jhazmat.2026.141086. Online ahead of print.

ABSTRACT

The escalating global incidence of male infertility is closely linked to environmental endocrine disruptors, particularly pesticides. Glyphosate (GLY) is a widely used pesticide with endocrine-disrupting activity and has been recognized to pose substantial public health risks. However, its impact on male reproductive health and the underlying mechanisms remains poorly defined. Thus, the present study established a 24-week mouse model of chronic GLY exposure to investigate its effects on spermatogenesis systematically. Pathological analysis revealed that GLY exposure damaged seminiferous tubules and induced sperm acrosomal defects. These defects originated from GLY-induced disruption of the Golgi apparatus, which impaired the accumulation and fusion of proacrosomal vesicles on spermatid nuclei. Integrated network toxicology and transcriptomics showed that autophagy is a critical mediator of GLY-induced Golgi damage and suppression of vesicle biosynthesis. Further analysis demonstrated that GLY triggered Golgi fragmentation and reduced proacrosomal vesicles via activating Golgiphagy. Importantly, knockdown of Golgi phosphoprotein 3 (GOLPH3), a novel Golgiphagy receptor, markedly attenuated GLY-induced Golgiphagy and restored the Golgi structure. Taken together, chronic GLY exposure compromises acrosome biogenesis during spermatogenesis by activating GOLPH3-mediated Golgiphagy, thereby impairing sperm quality. These findings provide a feasible therapeutic strategy to counteract the reproductive health threats posed by GLY and analogous environmental pollutants.

PMID:41512752 | DOI:10.1016/j.jhazmat.2026.141086

Environ Res. 2026 Jan 7:123730. doi: 10.1016/j.envres.2026.123730. Online ahead of print.

ABSTRACT

Few studies have explored the association of prenatal exposure to typical endocrine disrupting chemicals such as nonylphenol (NP) and bisphenols with the odds of precocious puberty (PP) in girls. To evaluate the associations of maternal exposure to NP and bisphenols during pregnancy with the odds of PP [including central PP (CPP) and incomplete PP (IPP) subtypes] in girls, this study included 87 CPP cases, 109 IPP cases, and 588 matched (1: 3) controls based on a Wuhan birth cohort (2012-2014). Maternal urinary concentrations of three bisphenols and two NP metabolites [including oxo-NP and hydroxy-NP (OH-NP)] were measured before delivery. Multivariable logistic regression and weighted quantile sum regression were applied to evaluate the relationships of the individual phenols and their mixture with the PP odds in the girls. Non-linear dose-response relationships were observed between oxo-NP and OH-NP and the PP odds (p for non-linearity < 0.05). Specifically, after false discovery rate (FDR) correction, the third quartile of OH-NP [odds ratio (OR): 1.42, 95% confidence interval (CI): 1.09-1.87; p_FDR = 0.01] and oxo-NP (OR: 1.52, 95% CI: 1.17-1.98; p_FDR = 0.002) showed significant associations with the overall PP odds. For PP subtypes, oxo-NP was significantly associated with CPP (the third quartile OR: 1.77, 95% CI: 1.17-2.68; p_FDR = 0.04). NP metabolites were identified as the major contributors to the phenol mixture associated with the CPP odds. Prenatal NP exposure may non-linearly increase the odds of PP in girls, particularly that of CPP, at moderate exposure levels, underscoring the need to reduce prenatal exposure and clarify the underlying mechanisms.

PMID:41512988 | DOI:10.1016/j.envres.2026.123730

Anal Chim Acta. 2026 Jan 22;1384:344978. doi: 10.1016/j.aca.2025.344978. Epub 2025 Dec 1.

ABSTRACT

Parabens, widely used as preservatives in pharmaceuticals and personal care products, are considered emerging contaminants due to their endocrine-disrupting properties and frequent detection in aquatic environments. Their trace-level concentrations (μg L^-1 to ng L^-1) and moderate polarity pose significant challenges for effective monitoring using conventional preconcentration techniques. To address these limitations, a green ultrasound-assisted extraction method was developed employing polyvinylpyrrolidone-alginate beads functionalized with a hydrophobic natural eutectic solvent composed of menthol and camphor (2:1 M ratio). The sorbent facilitates selective interaction with parabens through hydrogen bonding and hydrophobic effects, significantly improving extraction efficiency over non-functionalized materials. The method utilises only 125 mg of biodegradable sorbent and 3 % ammonia in water as desorption solvent, per analysis, minimising the use of hazardous reagent and aligning with Green Analytical Chemistry principles. Under optimised conditions, four parabens i.e., methylparaben, ethylparaben, propylparaben and butylparaben, were simultaneously extracted and analysed by UHPLC-DAD, achieving enrichment factors ranged from 8 to 13.9, with limits of detection and quantification between 0.056 and 0.222 μg L^-1 and 0.186-0.744 μg L^-1, respectively. Precision (RSD) remained below 10 % for both intra- and inter-day analyses, with excellent linearity (R² ≥ 0.9943) across a working range of 5-10,000 μg L^-1. The method was successfully applied to wastewater samples from various treatment stages, achieving recoveries between 81 and 114 %, confirming its suitability for routine environmental monitoring of parabens.

PMID:41513349 | DOI:10.1016/j.aca.2025.344978

Drug Chem Toxicol. 2026 Jan 8:1-19. doi: 10.1080/01480545.2025.2606102. Online ahead of print.

ABSTRACT

The thyroid gland is a central endocrine organ regulating growth, metabolism, and energy balance, and is increasingly vulnerable to interference by diverse xenobiotic compounds from pharmaceuticals, environmental pollutants, diet, and consumer products. This review introduces a thyroid '3H' framework - hormonogenesis, homeostasis, and human health - to integrate current understanding of how thyroid endocrine-disrupting chemicals (Thy-EDCs) perturb thyroid physiology and the hypothalamic-pituitary-thyroid axis. A systematic literature search was conducted using PubMed, Scopus, and Web of Science, supplemented by reference screening to ensure comprehensive coverage of mechanistic and toxicological evidence. The synthesis indicates that various exogenous compounds - including tyrosine kinase inhibitors, immune checkpoint inhibitors, heavy metals, industrial endocrine disruptors, and certain dietary phytochemicals - affect thyroid function through multiple molecular initiating events. These include inhibition of thyroperoxidase, disruption of iodine uptake and organification, altered deiodinase activity, modulation of thyroid hormone receptor signaling, and immune-mediated effects on thyroid tissue. Such perturbations lead to abnormalities in hormone synthesis, metabolism, and systemic hormone homeostasis. Emerging structure-activity relationship (SAR) and computational modeling approaches provide further insight into how specific chemical features determine thyroid-disruptive potential, supporting the advancement of predictive toxicology and risk assessment. The novelty of this review lies in its integrated 3H perspective, linking physiological, molecular, immunological, and toxicological dimensions of thyroid disruption. This conceptual framework supports improved diagnosis of thyroid dysfunction, promotes safer chemical and drug design, and informs regulatory strategies aimed at protecting endocrine health.

PMID:41504187 | DOI:10.1080/01480545.2025.2606102

Rev Environ Health. 2026 Jan 9. doi: 10.1515/reveh-2025-0106. Online ahead of print.

ABSTRACT

The increasing exposure to manufactured environmental pollutants, especially plastics, is linked to adverse neurological effects. While prenatal exposure to plastics has been associated with neurodevelopmental disorders, particularly autism, the role of this exposure in schizophrenia remains under-investigated. This narrative mini-review examines the potential impact of endocrine-disrupting plastics, e.g. bisphenols and phthalates, on schizophrenia onset risk. These chemicals are ubiquitous and pervasive neurotoxicants, implicated in neuroinflammation - a key feature of schizophrenia. Additionally, microplastics have been detected in human brains, raising concerns about their potential long-term impact on neurological health. Despite the growing evidence of plastic-induced neurodevelopmental harm, this issue has been neglected for schizophrenia, with scarce human or valid animal model literature available. Limited studies indicate that plastic chemicals cause behavioural deficits, hormonal dysregulation and altered brain function relevant to schizophrenia. Cumulative exposure to multiple plastic chemicals over the life course necessitates carefully designed approaches. Future studies should investigate the mechanisms by which plastics contribute to schizophrenia risk. Epidemiological research with multi-omic approaches is needed to strengthen regulatory action and inform exposure prevention strategies particularly in high-risk populations. Given the increasing burden of environmental pollutants, urgent attention is required to address their role in neurodevelopmental disorders, particularly schizophrenia.

PMID:41505220 | DOI:10.1515/reveh-2025-0106

PLoS One. 2026 Jan 8;21(1):e0333081. doi: 10.1371/journal.pone.0333081. eCollection 2026.

ABSTRACT

OBJECTIVE: Abnormal body mass index (BMI) has been associated with pregnancy complications and adverse pregnancy outcomes; however, its clinical significance during early pregnancy remains unclear. This study aimed to investigate the relationships and underlying mechanisms between maternal BMI, reproductive endocrine parameters, and pregnancy outcomes, thereby providing a theoretical basis and clinical guidance for the management of pregnancies in women with abnormal BMI.

METHODS: A total of 353 pregnant women were enrolled in this study and categorized into four groups according to BMI: underweight (n = 45), normal weight (n = 229), overweight (n = 57), and obese (n = 22). At 6-8 weeks of gestation, pregnancy-related hormones, glucose and lipid metabolism parameters, and uterine artery blood flow indices were collected and analyzed. Pregnancy outcomes and neonatal birth information were also recorded. In addition, an obese mouse model was established to evaluate maternal weight changes during pregnancy and their effects on uterine and embryonic development. The expression of genes and proteins related to en[docrine metabolism, inflammatory regulation, and angiogenesis was assessed using RT-qPCR and Western blot techniques to further explore the potential mechanisms involved.

RESULTS: During early pregnancy, pregnant women with low BMI exhibited significantly lower estradiol levels (P < 0.05). In contrast, women with high BMI had significantly reduced levels of human chorionic gonadotropin, estradiol, and progesterone, along with markedly elevated glucose and lipid metabolism parameters (P < 0.05). However, BMI had no significant impact on uterine artery blood flow indices, live birth rate, gestational age, or mode of delivery (P > 0.05). High BMI was associated with an increased risk of macrosomia in neonates (P < 0.05). In the animal experiments, obese pregnant mice exhibited significantly greater gestational weight gain compared to controls (P < 0.05), and their offspring showed a predisposition to obesity. RT-qPCR analysis revealed that, relative to the control group, mRNA expression levels of VEGFA, VEGFR-2, CD31, and SIRT1 were significantly decreased in the obese group (P < 0.001), whereas mRNA expression of GLUT1, HIF-1α, TNF-α, IL-6, HMGB1, and TLR4 was significantly upregulated (P < 0.01). Western blot results demonstrated that compared with controls, the obese group showed significantly lower expression levels of GLUT4 and phosphorylated IRS1 (P < 0.0001), while the expression of HIF-1α and TNF-α was significantly increased (P < 0.0001). Additionally, there were no significant differences in the protein expression levels of IRS1, SGK1, and NFκB p65 between the two groups (P > 0.05).

CONCLUSION: Abnormal BMI affects hormonal profiles and glucose and lipid metabolism during early pregnancy. Although it does not significantly impact fetal survival rates, it markedly increases the risks of cesarean delivery, preterm birth, and abnormal neonatal birth weight. These alterations not only pose challenges for postpartum maternal and neonatal health management but may also exert adverse effects on the long-term health of the offspring. Maternal obesity may impair pregnancy outcomes by inhibiting insulin signaling, enhancing proinflammatory responses, inducing a hypoxic microenvironment in the decidual tissue, and suppressing angiogenesis, thereby disrupting maternal-fetal interface homeostasis.

PMID:41505418 | PMC:PMC12782434 | DOI:10.1371/journal.pone.0333081

Rev Environ Health. 2026 Jan 9. doi: 10.1515/reveh-2025-0106. Online ahead of print.

ABSTRACT

The increasing exposure to manufactured environmental pollutants, especially plastics, is linked to adverse neurological effects. While prenatal exposure to plastics has been associated with neurodevelopmental disorders, particularly autism, the role of this exposure in schizophrenia remains under-investigated. This narrative mini-review examines the potential impact of endocrine-disrupting plastics, e.g. bisphenols and phthalates, on schizophrenia onset risk. These chemicals are ubiquitous and pervasive neurotoxicants, implicated in neuroinflammation - a key feature of schizophrenia. Additionally, microplastics have been detected in human brains, raising concerns about their potential long-term impact on neurological health. Despite the growing evidence of plastic-induced neurodevelopmental harm, this issue has been neglected for schizophrenia, with scarce human or valid animal model literature available. Limited studies indicate that plastic chemicals cause behavioural deficits, hormonal dysregulation and altered brain function relevant to schizophrenia. Cumulative exposure to multiple plastic chemicals over the life course necessitates carefully designed approaches. Future studies should investigate the mechanisms by which plastics contribute to schizophrenia risk. Epidemiological research with multi-omic approaches is needed to strengthen regulatory action and inform exposure prevention strategies particularly in high-risk populations. Given the increasing burden of environmental pollutants, urgent attention is required to address their role in neurodevelopmental disorders, particularly schizophrenia.

PMID:41505220 | DOI:10.1515/reveh-2025-0106

Aquat Toxicol. 2026 Jan 5;291:107708. doi: 10.1016/j.aquatox.2026.107708. Online ahead of print.

ABSTRACT

Steroid hormones, such as androstadienedione (ADD), androstenedione (AED), and estrone (E1), are widespread and persistent in various aquatic environments. However, their combined effects on aquatic organisms remain poorly understood. In this study, western mosquitofish (Gambusia affinis) were exposed throughout their life cycle to low and high concentrations of ADD (100 and 10000 ng/L), AED (100 and 10000 ng/L), E1 (100 and 5000 ng/L), and binary mixtures of each androgen (ADD or AED) with E1 at their respective low and high concentrations. The effects of these treatments on sex ratio, condition factors, gonadal development, sexual dimorphism, and hypothalamic-pituitary-gonadal-liver axis-related gene transcription were assessed. A high concentration of ADD or AED significantly increased male-biased sex ratios (1.2-fold increase); however, this effect was attenuated in combination with a high concentration of E1. Notably, in males, a high concentration of ADD acted synergistically with E1, increasing the proportion of immature spermatocytes and downregulating amh transcriptional expression, thereby exacerbating testicular damage and reproductive toxicity. In contrast, in females, ADD or AED may antagonize E1, reducing oocyte degeneration rates and mitigating steroid-mediated disruption in fish. Overall, exposure to these hormones, whether alone or in combination, impairs gene expression and gonad development in G. affinis, but these effects exhibit sex-specific differences. These findings highlight the complex and sex-specific nature of endocrine disruption caused by steroid hormone mixtures in aquatic environments.

PMID:41506192 | DOI:10.1016/j.aquatox.2026.107708

Phytother Res. 2026 Jan 8. doi: 10.1002/ptr.70158. Online ahead of print.

ABSTRACT

Ashwagandha (Withania somnifera) is a herbal adaptogen which has been extensively studied for its wide-ranging medicinal properties, ranging from stress relief to neuroprotection and immune modulation. Recent studies have evoked concerns over the toxicity of the bioactive compounds, including withanolides, alkaloids, and sitoindosides. Gastrointestinal side effects, immune hypersensitivity, liver toxicity, and endocrine disruption have been reported, particularly with prolonged or excessive usage. Metabolic transformation via cytochrome P450 enzymes can form reactive intermediates, leading to oxidative stress and hepatotoxicity. The endocrine-modulating activity of Ashwagandha has been implicated in thyrotoxicosis and adrenal suppression. This review provides a comprehensive overview of the pharmacological profiles, incorporating preclinical and clinical data to illustrate the fine balance between the therapeutic and toxic effects of Ashwagandha, identifying populations that may be at increased risk of adverse reactions and interactions with prescribed drugs for specific conditions. The necessity for standardizing dosing regimens, rigorous clinical trials, improving pharmacovigilance, carrying out long-term safety assessments, and revising regulatory guidelines is emphasized to maximize clinical application of Ashwagandha while minimizing concomitant risks.

PMID:41502355 | DOI:10.1002/ptr.70158

Insect Sci. 2026 Jan 8. doi: 10.1111/1744-7917.70213. Online ahead of print.

ABSTRACT

Insects, the most diverse group of animals, inhabit almost all environments on Earth. They are susceptible to a wide range of parasites, including entomopathogenic protozoans, nematodes, and ectoparasitic mites. These parasites manipulate host physiology via immunomodulation, endocrine disruption, and metabolic reprogramming. The long-term coexistence of insects and parasites has driven the evolution of intricate survival strategies. Insects deploy morphological, physiological, and behavioral adaptations to mitigate infection risks, whereas parasites counter with sophisticated mechanisms enhancing transmission and reproductive success. Emerging evidence indicates symbiotic microbiota as critical mediators in this evolutionary arms race, modulating infection outcomes through microbial-host-parasite crosstalk. Here, we review recent research progress on the effects of parasites on the development, reproduction, immunity, and behavior of insect hosts; the evolutionary dynamics between insects and parasites; and the interactions of host-parasite-microbiota in insects. Compared to mammals, insects provide a simple model system for elucidating conserved molecular mechanisms underlying host-parasite-gut microbiota interactions. This paradigm not only advances fundamental understanding of evolutionary parasitology but also pioneers microbial-based biocontrol approaches, offering sustainable alternatives for agricultural pest management and economic insect conservation.

PMID:41503922 | DOI:10.1111/1744-7917.70213

Toxicol Res. 2025 Sep 8;42(1):83-98. doi: 10.1007/s43188-025-00316-w. eCollection 2026 Jan.

ABSTRACT

Flame retardants are integral components in numerous consumer and industrial products. Accumulating research has shown that retardants disrupt the endocrine system via the modulation of thyroid hormone receptors (THRs). To investigate the mechanisms underlying this effect, we established a luciferase reporter assay system using HEK293 cells expressing the human THR isomers THRα and THRβ, and screened six flame-retardant compounds with agonistic or antagonistic activity. We examined THR agonism or antagonism in these compounds, which included organophosphate (tris(3-chloropropyl) phosphate), bisphenol-type (tetrabromobisphenol A), and brominated compounds (decabromodiphenyl ethane [DBDPEthane], decabromodiphenyl ether [DBDPEther], 1,2-bis(2,4,6-tribromophenoxy) ethane, and DC604). Among these, DBDPEthane, a widely used flame retardant, has emerged as a potential endocrine-disrupting chemical. The structurally related compounds DBDPEther and DBDPEthane were found to exert antagonistic effects on both THRα and THRβ. To elucidate the molecular basis of this antagonism, molecular docking analysis was performed using the ligand-binding domains of THRα and THRβ. The results indicated binding of DBDPEthane within ligand-binding pockets of both THRα and THRβ, forming specific hydrogen bonds and hydrophobic interactions that may support its antagonistic effects. To further characterize the dynamic interactions between DBDPEthane and THRα or THRβ, we conducted molecular dynamics simulations, using the root mean square deviation (RMSD), root mean square fluctuation (RMSF), and solvent-accessible surface area (SASA) as metrics. The results revealed distinct binding stability and conformational flexibility between DBDPEthane and THRβ, supported by RMSD, RMSF and SASA. These findings highlight the potential of DBDPEthane to antagonize both THRα and THRβ, providing functional and structural insights into its thyroid-disrupting properties in the context of receptor subtype selectivity.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43188-025-00316-w.

PMID:41503439 | PMC:PMC12770159 | DOI:10.1007/s43188-025-00316-w

Bull Exp Biol Med. 2026 Jan 8. doi: 10.1007/s10517-026-06545-9. Online ahead of print.

ABSTRACT

The morphological and functional parameters of the spleen development during pubertal period were studied in rats exposed to low doses of the endocrine disruptor dichlorodiphenyltrichloroethane (DDT) in the prenatal and postnatal periods. Despite the spleen weight and the amount of lymphoid tissue in it were similar to the control values, delayed formation of germinal centers in lymphoid nodules and impaired migration of neutrophils to the red pulp and marginal zone were revealed in DDT-exposed rats. Along with these signs, the processes of hematopoiesis were more active in the spleen, which in general indicates a delay in its functional maturation as an organ of the immune system and increases the risk of impaired development of immune reactions.

PMID:41507477 | DOI:10.1007/s10517-026-06545-9

Environ Health. 2026 Jan 7. doi: 10.1186/s12940-025-01261-9. Online ahead of print.

ABSTRACT

BACKGROUND: Arsenic is a pervasive environmental contaminant and a recognized global public health concern. Experimental evidence suggests that arsenic may disrupt endocrine signaling during critical developmental windows, yet epidemiologic data on its effects on thyroid function in early childhood remain limited.

METHODS: We investigated the cross-sectional association between arsenic exposure and free thyroxine (fT4) levels among 496 children aged 5 to 7 years enrolled in the Bangladesh Environmental Research in Children's Health (BiRCH) cohort. Arsenic exposure was assessed using urinary total arsenic and toenail arsenic concentrations. Serum fT4 levels were measured by an enzyme-linked immunosorbent assay (ELISA) kit. Associations with fT4 were estimated using multivariable linear regression models adjusted for child age, sex, body mass index, and environmental tobacco smoke exposure.

RESULTS: The median urinary and toenail arsenic concentrations were 88.0 µg/L (interquartile range [IQR]: 127.4) and 1.7 µg/g (IQR: 2.0), respectively. Children in the highest quartile (Q4) of arsenic exposure had significantly higher fT4 levels compared to those in the lowest quartile (Q1), for both urinary (β = 0.09; 95% CI: 0.005-0.17) and toenail arsenic (β = 0.10; 95% CI: 0.03-0.17). A significant dose-response trend was observed across quartiles, suggesting a potential linear relationship.

CONCLUSIONS: Our findings suggest that thyroid function may be a sensitive target of arsenic toxicity in early childhood. Longitudinal studies are necessary to assess the long-term effects of early-life arsenic exposure on thyroid function across the life course.

PMID:41501906 | DOI:10.1186/s12940-025-01261-9

J Hazard Mater. 2026 Jan 6;502:141070. doi: 10.1016/j.jhazmat.2026.141070. Online ahead of print.

ABSTRACT

Environmental exposures are increasingly recognized as key modulators of the epigenome, contributing to both immediate and long-term disease risk. The field of toxicoepigenomics, which investigates how environmental toxicants alter epigenetic regulation, has demonstrated that exposures to endocrine-disrupting chemicals, heavy metals, polycyclic aromatic hydrocarbons (PAHs), and air pollutants can disrupt gene expression through changes in DNA methylation, histone modifications, non-coding RNA expression, and higher-order chromatin structure. Additionally, lifestyle factors-including diet, physical activity, stress, and sleep-interact with these exposures to shape individual epigenetic profiles and influence health trajectories across the lifespan. This review synthesizes current evidence across major pollutant classes and molecular pathways, emphasizing both well-characterized and emerging mechanisms. Retained introns represent post-transcriptional consequences of chromatin-based epigenetic regulation and serve as sensitive indicators of environmentally induced disruptions in transcriptional elongation and splicing fidelity. We also highlight recent advances in high-throughput technologies, including whole-genome bisulfite sequencing, single-cell epigenomics, and epigenetic clock models, which are rapidly enhancing biomarker discovery and mechanistic understanding. By integrating multilayered epigenetic insights across diverse exposure contexts, this review advances the field of toxicoepigenomics and lays the groundwork for developing robust, exposure-responsive biomarkers of environmental disease. These insights offer significant promise for guiding mechanistic research, improving exposure surveillance, and informing the design of precision strategies in environmental health.

PMID:41506210 | DOI:10.1016/j.jhazmat.2026.141070

Mar Pollut Bull. 2026 Jan 6;225:119211. doi: 10.1016/j.marpolbul.2025.119211. Online ahead of print.

ABSTRACT

Benzo[a]pyrene (BaP), a high-molecular-weight polycyclic aromatic hydrocarbon, is a persistent contaminant with well-documented developmental and endocrine-disrupting effects in aquatic organisms. This study examined how reproductive timing after exposure cessation influences transgenerational toxicity in marine medaka (Oryzias melastigma). Fish were exposed to environmentally relevant BaP concentrations (1, 4, and 8 μg/L) for 120 days, and F1 offspring were obtained from parents spawning 1, 30, and 60 days post-exposure. Offspring from 1-day post-exposure spawns showed up to 40 % reduced hatching, elevated mortality, malformations, and shorter body length, accompanied by downregulation of antioxidant (sod, cat, gpx) and steroidogenic (cyp17a, 17βhsd, cyp11b) genes and elevated thyroglobulin (tg) and vitellogenin (vtg1, vtg2). Partial recovery occurred in oxidative and apoptotic pathways at 30 days, while endocrine and growth disruptions persisted. By 60 days, most parameters normalized except thyroid- and growth-axis markers. Hormonal assays revealed increased adrenocorticotropic hormone, cortisol, elevated thyroxine, and suppressed growth hormone, indicating slow endocrine and growth recovery.

PMID:41499999 | DOI:10.1016/j.marpolbul.2025.119211

Sci One Health. 2025 Aug 26;4:100121. doi: 10.1016/j.soh.2025.100121. eCollection 2025.

ABSTRACT

Crustaceans, widely consumed and ecologically significant marine organisms, are increasingly affected by microplastic (MP) pollution, one of the most pressing environmental challenges of the 21st century. These benthic and pelagic species, including shrimp, crabs, and lobsters, play essential roles in nutrient cycling, food web dynamics, and global seafood supply. The proliferation of plastic waste has led to widespread MP contamination in marine environments, threatening both ecological stability and human health. This review provides an in-depth overview of MP pollution, its ingestion and accumulation in crustaceans, and the resulting biological and toxicological effects. Data were compiled from leading academic databases, including Scopus, Web of Science, PubMed, ScienceDirect, and Google Scholar, with 54 peer-reviewed articles selected for synthesis. Fibers, fragments, films, and beads were the most frequently reported MP types, predominantly found in the digestive tracts, gills, and hepatopancreas of decapod crustaceans. These particles can cause oxidative stress, inflammation, reproductive disruption, and immune system impairment in crustaceans, while also acting as vectors for hazardous chemicals such as heavy metals and endocrine-disrupting compounds. The consumption of contaminated crustaceans poses potential health risks to humans, including gastrointestinal disorders, hormonal imbalances, and carcinogenic effects. Despite rapid progress in this field, major gaps remain in understanding the long-term ecological and human health impacts, particularly in less-studied regions and species. Further global investigations, long-term ecological assessments, and public awareness initiatives are essential. Effective mitigation will require interdisciplinary collaboration, technological innovation, and sustainable waste management to ensure a healthier marine ecosystem and safer seafood consumption.

PMID:41498120 | PMC:PMC12766094 | DOI:10.1016/j.soh.2025.100121

Sci One Health. 2025 Aug 26;4:100121. doi: 10.1016/j.soh.2025.100121. eCollection 2025.

ABSTRACT

Crustaceans, widely consumed and ecologically significant marine organisms, are increasingly affected by microplastic (MP) pollution, one of the most pressing environmental challenges of the 21st century. These benthic and pelagic species, including shrimp, crabs, and lobsters, play essential roles in nutrient cycling, food web dynamics, and global seafood supply. The proliferation of plastic waste has led to widespread MP contamination in marine environments, threatening both ecological stability and human health. This review provides an in-depth overview of MP pollution, its ingestion and accumulation in crustaceans, and the resulting biological and toxicological effects. Data were compiled from leading academic databases, including Scopus, Web of Science, PubMed, ScienceDirect, and Google Scholar, with 54 peer-reviewed articles selected for synthesis. Fibers, fragments, films, and beads were the most frequently reported MP types, predominantly found in the digestive tracts, gills, and hepatopancreas of decapod crustaceans. These particles can cause oxidative stress, inflammation, reproductive disruption, and immune system impairment in crustaceans, while also acting as vectors for hazardous chemicals such as heavy metals and endocrine-disrupting compounds. The consumption of contaminated crustaceans poses potential health risks to humans, including gastrointestinal disorders, hormonal imbalances, and carcinogenic effects. Despite rapid progress in this field, major gaps remain in understanding the long-term ecological and human health impacts, particularly in less-studied regions and species. Further global investigations, long-term ecological assessments, and public awareness initiatives are essential. Effective mitigation will require interdisciplinary collaboration, technological innovation, and sustainable waste management to ensure a healthier marine ecosystem and safer seafood consumption.

PMID:41498120 | PMC:PMC12766094 | DOI:10.1016/j.soh.2025.100121

J Toxicol. 2025 Dec 9;2025:5569113. doi: 10.1155/jt/5569113. eCollection 2025.

ABSTRACT

BACKGROUND: Microplastics (MPs) and the endocrine-disrupting chemicals associated with them, including bisphenol A (BPA) and phthalates, have been identified as potential factors contributing to the increasing rates of metabolic syndrome (MetS) and colorectal carcinogenesis. Despite rising concerns in this area, a thorough synthesis of the mechanistic and epidemiological data connecting MPs to these health issues is currently absent. For consistency in this review, early-onset colorectal cancer is defined as colorectal cancer diagnosed before the age of 50 years, in line with recent epidemiological studies. Chronic exposure to MPs is defined as sustained exposure lasting at least 8 weeks in animal models or multiple years in human observational studies. These standardized definitions ensure clarity when comparing outcomes across diverse study designs.

OBJECTIVE: This systematic review aims to evaluate current human, animal, and in vitro evidence on the dual impact of MP exposure on metabolic dysregulation and pathways involved in colorectal carcinogenesis.

METHODS: A systematic search was performed across PubMed, Scopus, Web of Science, and EMBASE in accordance with PRISMA 2020 guidelines. The review incorporated 45 studies: 18 observational studies involving humans, 17 animal studies, and 10 in vitro investigations. The outcomes analyzed included components of MetS, precursors to colonic neoplasia, and relevant biological mechanisms.

RESULTS: Exposure to MPs correlated with an increased risk of insulin resistance, obesity, and dyslipidemia. It also contributed to heightened inflammatory responses, alterations in gut microbiota composition, and dysfunction of the epithelial barrier. Furthermore, chronic exposure led to colonic inflammation and an elevation in tumorigenic markers, such as β-catenin (a key oncogenic protein in the Wnt signaling pathway) and COX-2 (an inflammatory enzyme implicated in tumor progression).

CONCLUSION: The results indicate a biologically plausible connection between MP exposure and the development of both MetS and colorectal carcinogenesis pathways, rather than a direct clinical association with early-onset colorectal cancer.

PMID:41498107 | PMC:PMC12767036 | DOI:10.1155/jt/5569113

Arch Womens Ment Health. 2026 Jan 7;29(1):10. doi: 10.1007/s00737-025-01657-z.

ABSTRACT

PROPOSE: To examine how chronic psychological stress alters gonadotropin dynamics and disrupts ovarian endocrine function in women with polycystic ovarian morphology (PCOM), and to discuss the modulatory role of leptin in this process.

METHODS: In this cross-sectional study of 134 women, participants were classified into four groups: three subgroups of women with oligomenorrhea-PCOM with stress, PCOM without stress, and NON-PCOM/NON-STRESS-and a comparison group of eumenorrheic controls. Psychological stress was assessed with validated psychometric instruments (STAI, HADS, PSS-10), and a composite Stress Index was derived. PCOM was defined according to the 2023 International Evidence-based Guideline for PCOS. Stress status was classified using established cut-offs for each instrument, with non-stress cohorts defined by scores consistently below clinical thresholds. Hormonal profiling included LH, FSH, estradiol, AMH, leptin, cortisol, and ACTH. Mediation and moderation models were employed to examine the relationships among stress, leptin, the LH/FSH ratio, and ovarian endocrine markers, as AMH and estradiol.

RESULTS: Women in the PCOM-STRESS group exhibited significantly lower LH levels, LH/FSH ratios, and AMH concentrations compared to PCOM-NON-STRESS, despite similar ovarian morphology and preserved FSH levels. Mediation analysis revealed that the LH/FSH ratio significantly mediated the effect of psychological stress on both estradiol and AMH levels. Moderation analysis indicated that leptin modulated the impact of stress on the LH/FSH ratio (interaction p = 0.004), with more pronounced suppressive effects of psychological stress under low leptin levels. Despite high psychological stress, women in the PCOM-STRESS group showed no activation of the HPA axis, suggesting neuroendocrine resilience or adaptation. These findings highlight the clinical value of assessing both psychological and metabolic context in women with ambiguous ovulatory dysfunction.

CONCLUSION: Chronic psychological stress in women with PCOM is associated with functional suppression of LH and ovarian endocrine output, reflecting an attenuation of the typical PCOS endocrine phenotype despite the polycystic ovarian morphology. Leptin modulates individual susceptibility to stress-induced reproductive suppression, acting as a potential permissive signal of hypothalamic resilience. Assessing gonadotropin ratios and metabolic context may improve diagnostic accuracy in women with ambiguous ovulatory dysfunction.

PMID:41498876 | PMC:PMC12779685 | DOI:10.1007/s00737-025-01657-z

J Hazard Mater. 2026 Jan 2;502:141006. doi: 10.1016/j.jhazmat.2025.141006. Online ahead of print.

ABSTRACT

Male reproductive toxicity tests are a standard component of toxicological research, regulatory and safety assessment during drug development and environmental biomonitoring. Zebrafish (Danio rerio) has emerged as a valuable model for studying male reproductive toxicity, particularly through sperm toxicity tests. Thus, this review systematically analyzed the scientific literature concerning the Zebrafish Sperm Toxicity test (ZST), focusing on the effects of environmental chemicals on sperm quality and reproductive health. Results showed that over 80 chemicals have been studied for their adverse effects on zebrafish sperm, including synthetic estrogens, metals, pesticides, and antibiotics. Several endocrine disruptors, such as bisphenol A (BPA) and tributyltin (TBT), impairing sperm count, motility, and morphology by disrupting hormonal regulation and inducing oxidative stress. Methodological approaches were discussed, including sperm collection techniques and storage media, which are critical for experimental reproducibility. Exposure times vary widely, with chronic and long-term exposures being more common in in vivo studies, while in vitro studies typically involve shorter exposure periods. The most frequently adverse effects on zebrafish sperm were reduced sperm count, volume or density, motility, DNA and membrane integrity, and morphological alterations, with endocrine disruption being a primary mechanism of action and toxicity. The review underscores the need for standardized protocols and further research on emerging pollutants, transgenerational effects, and the development of advanced in vitro models to reduce reliance on in vivo experiments. Overall, the zebrafish sperm toxicity test is a suitable tool for assessing the impact of environmental contaminants on reproductive health, helping to protect human and environmental health.

PMID:41499865 | DOI:10.1016/j.jhazmat.2025.141006

Clin Nutr. 2025 Dec 29;57:106555. doi: 10.1016/j.clnu.2025.106555. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: The non-degradable poly- and perfluoroalkyl substances (PFAS) are 'Endocrine Disrupting Chemicals' (EDCs), a group of chemicals that interfere with endocrine processes in the human body and potentially have adverse effects on several developmental domains in children. Particularly when PFAS exposure occurs during susceptive periods, including 'the first 1000 days' of life. Human milk is an important PFAS exposure pathway. In contrast to breastfeeding, PFAS have been thought to negatively influence growth, body composition development and metabolic health. However, exact mechanisms are not yet unraveled. Potential pathways might be via appetite regulating hormones (ARHs) and eating behavior. We, therefore, investigated the influence of feeding type (exclusive breastfeeding (EBF), exclusive formula feeding (EFF) or mixed feeding (mix)) on plasma ARHs and eating behavior and also the associations between plasma PFAS levels, ARHs and eating behavior, in infants during the first 2 years of life.

METHODS: This study was embedded in the Sophia Pluto study. We conducted longitudinal follow-up in 371 healthy term-born infants (150 EBF, 97 EFF and 124 mix) during the first 2 years of life. At age 3 months and 2 years, we studied eating behavior via the Baby Eating Behavior Questionnaire (BEBQ) and Child Eating Behavior Questionnaire (CEBQ), respectively. At these timepoints, fasting blood samples were collected in which plasma levels of 5 individual PFAS and 9 ARHs were determined. The associations of plasma PFAS levels and feeding type with ARHs and eating behavior were studied using multiple regression models, corrected for known confounders, such as sex and fat mass SDS.

RESULTS: At age 3 months plasma ARH levels differed between children that were EBF, EFF and mix. With EBF-infants having the highest levels of peptide YY (PYY) and the lowest of insulin, amylin and pancreatic polypeptide (PP). These differences disappeared at age 2 years. Higher plasma PFAS levels, corrected for feeding type, at age 3 months were associated with higher adiponectin and lower leptin levels and at age 2 years with lower leptin and insulin levels. When studying eating behavior, we did neither find any differences between EBF, EFF and mix infants at age 3 months nor at age 2 years. At age 3 months, plasma PFAS levels were inversely associated with "food responsiveness", and positively with "slowness in eating". At age 2 years, plasma PFAS levels, corrected for feeding type, were inversely associated with all "food approach" subscales.

CONCLUSION: Our findings could indicate that PFAS exposure does not compromise breastfeeding's health benefits on metabolic health and insulin sensitivity until age 2 years and that PFAS exposure probably effects eating behavior via other pathways than ARHs alone, which warrants further research.

PMID:41499922 | DOI:10.1016/j.clnu.2025.106555

J Toxicol. 2025 Dec 9;2025:5569113. doi: 10.1155/jt/5569113. eCollection 2025.

ABSTRACT

BACKGROUND: Microplastics (MPs) and the endocrine-disrupting chemicals associated with them, including bisphenol A (BPA) and phthalates, have been identified as potential factors contributing to the increasing rates of metabolic syndrome (MetS) and colorectal carcinogenesis. Despite rising concerns in this area, a thorough synthesis of the mechanistic and epidemiological data connecting MPs to these health issues is currently absent. For consistency in this review, early-onset colorectal cancer is defined as colorectal cancer diagnosed before the age of 50 years, in line with recent epidemiological studies. Chronic exposure to MPs is defined as sustained exposure lasting at least 8 weeks in animal models or multiple years in human observational studies. These standardized definitions ensure clarity when comparing outcomes across diverse study designs.

OBJECTIVE: This systematic review aims to evaluate current human, animal, and in vitro evidence on the dual impact of MP exposure on metabolic dysregulation and pathways involved in colorectal carcinogenesis.

METHODS: A systematic search was performed across PubMed, Scopus, Web of Science, and EMBASE in accordance with PRISMA 2020 guidelines. The review incorporated 45 studies: 18 observational studies involving humans, 17 animal studies, and 10 in vitro investigations. The outcomes analyzed included components of MetS, precursors to colonic neoplasia, and relevant biological mechanisms.

RESULTS: Exposure to MPs correlated with an increased risk of insulin resistance, obesity, and dyslipidemia. It also contributed to heightened inflammatory responses, alterations in gut microbiota composition, and dysfunction of the epithelial barrier. Furthermore, chronic exposure led to colonic inflammation and an elevation in tumorigenic markers, such as β-catenin (a key oncogenic protein in the Wnt signaling pathway) and COX-2 (an inflammatory enzyme implicated in tumor progression).

CONCLUSION: The results indicate a biologically plausible connection between MP exposure and the development of both MetS and colorectal carcinogenesis pathways, rather than a direct clinical association with early-onset colorectal cancer.

PMID:41498107 | PMC:PMC12767036 | DOI:10.1155/jt/5569113

Diabetes Metab Syndr Obes. 2025 Dec 31;18:4873-4911. doi: 10.2147/DMSO.S579409. eCollection 2025.

ABSTRACT

BACKGROUND: The developmental origins of health and disease (DOHaD) framework highlights the importance of the intrauterine environment in shaping lifelong health outcomes. Maternal nutrition, toxic exposures, and epigenetic reprogramming are key factors influencing offspring susceptibility to obesity and cardiometabolic disorders. However, prior reviews have typically addressed nutrition and toxicants separately, limiting insights into their combined effects on the fetal epigenome. This review integrates current evidence on how maternal nutrition and toxicant exposures converge through epigenetic mechanisms to influence obesity risk, while outlining translational opportunities for mitigating intergenerational metabolic disease.

METHODS: A narrative review was conducted of studies published from 2000 to 2025, sourced from PubMed, Scopus, and Web of Science, supplemented by manual screening. Search terms included maternal nutrition, environmental toxicants, epigenetic mechanisms, and offspring obesity outcomes. Studies on animal models, human cohorts, and intervention trials were included, focusing on links between maternal exposures, epigenetic changes, and metabolic disease.

RESULTS: Maternal dietary imbalances, such as deficiencies in one-carbon donors or excess caloric intake, cause persistent epigenetic changes on genes regulating adipogenesis and energy homeostasis, increasing offspring obesity risk. Prenatal exposure to environmental toxicants, including endocrine disruptors and heavy metals, amplifies these vulnerabilities by altering DNA methylation, histone modifications, and noncoding RNA networks. Combined nutritional deficits and toxicant exposures, particularly in low- and middle-income countries (LMICs), create a "dual burden" that intensifies epigenetic instability. Nutrients like methyl donors and antioxidants may mitigate toxicant-induced epimutations, offering potential for precision maternal nutrition interventions.

CONCLUSION: Maternal nutrition and toxicant exposures interact through epigenetic mechanisms to program obesity and related diseases. Addressing these factors through precision nutrition, stricter environmental regulations, and early-life epigenetic biomarkers offers promising prevention strategies. Large, diverse, multi-generational cohorts and multi-omics approaches are needed to strengthen causal inference and inform equitable policies to break the intergenerational cycle of metabolic disease.

PMID:41497887 | PMC:PMC12765939 | DOI:10.2147/DMSO.S579409

Clin Nutr. 2025 Dec 29;57:106555. doi: 10.1016/j.clnu.2025.106555. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: The non-degradable poly- and perfluoroalkyl substances (PFAS) are 'Endocrine Disrupting Chemicals' (EDCs), a group of chemicals that interfere with endocrine processes in the human body and potentially have adverse effects on several developmental domains in children. Particularly when PFAS exposure occurs during susceptive periods, including 'the first 1000 days' of life. Human milk is an important PFAS exposure pathway. In contrast to breastfeeding, PFAS have been thought to negatively influence growth, body composition development and metabolic health. However, exact mechanisms are not yet unraveled. Potential pathways might be via appetite regulating hormones (ARHs) and eating behavior. We, therefore, investigated the influence of feeding type (exclusive breastfeeding (EBF), exclusive formula feeding (EFF) or mixed feeding (mix)) on plasma ARHs and eating behavior and also the associations between plasma PFAS levels, ARHs and eating behavior, in infants during the first 2 years of life.

METHODS: This study was embedded in the Sophia Pluto study. We conducted longitudinal follow-up in 371 healthy term-born infants (150 EBF, 97 EFF and 124 mix) during the first 2 years of life. At age 3 months and 2 years, we studied eating behavior via the Baby Eating Behavior Questionnaire (BEBQ) and Child Eating Behavior Questionnaire (CEBQ), respectively. At these timepoints, fasting blood samples were collected in which plasma levels of 5 individual PFAS and 9 ARHs were determined. The associations of plasma PFAS levels and feeding type with ARHs and eating behavior were studied using multiple regression models, corrected for known confounders, such as sex and fat mass SDS.

RESULTS: At age 3 months plasma ARH levels differed between children that were EBF, EFF and mix. With EBF-infants having the highest levels of peptide YY (PYY) and the lowest of insulin, amylin and pancreatic polypeptide (PP). These differences disappeared at age 2 years. Higher plasma PFAS levels, corrected for feeding type, at age 3 months were associated with higher adiponectin and lower leptin levels and at age 2 years with lower leptin and insulin levels. When studying eating behavior, we did neither find any differences between EBF, EFF and mix infants at age 3 months nor at age 2 years. At age 3 months, plasma PFAS levels were inversely associated with "food responsiveness", and positively with "slowness in eating". At age 2 years, plasma PFAS levels, corrected for feeding type, were inversely associated with all "food approach" subscales.

CONCLUSION: Our findings could indicate that PFAS exposure does not compromise breastfeeding's health benefits on metabolic health and insulin sensitivity until age 2 years and that PFAS exposure probably effects eating behavior via other pathways than ARHs alone, which warrants further research.

PMID:41499922 | DOI:10.1016/j.clnu.2025.106555

Indian J Endocrinol Metab. 2025 Nov-Dec;29(6):590-594. doi: 10.4103/ijem.ijem_88_25. Epub 2025 Dec 19.

ABSTRACT

The escalating burden of carbon overload, largely driven by fossil fuel combustion, deforestation, and industrial activities, is a major contributor to climate change, leading to significant environmental and health consequences. Beyond its ecological implications, emerging evidence highlights the profound impact of climate change on human health, particularly on endocrine function. Rising global temperatures, increased exposure to particulate matter, endocrine-disrupting chemicals (EDCs), and shifts in dietary patterns pose significant challenges to hormonal homeostasis. This review critically examines the intricate relationship between carbon emissions, climate change, environmental pollutants, and endocrine disorders, including diabetes, thyroid dysfunction, reproductive health, and metabolic diseases. Additionally, we discuss potential mitigation strategies-including policy interventions, dietary modifications, and sustainable lifestyle practices-to safeguard endocrine health while addressing environmental sustainability. Recognizing and addressing the endocrine implications of climate change is essential for developing effective public health interventions aimed at mitigating long-term health risks.

PMID:41497296 | PMC:PMC12768322 | DOI:10.4103/ijem.ijem_88_25

bioRxiv [Preprint]. 2025 Dec 22:2025.12.18.695265. doi: 10.64898/2025.12.18.695265.

ABSTRACT

I. Several environmentally ubiquitous endocrine disrupting chemicals (EDCs) are suspected carcinogens, but their mechanism(s) of action are unknown. In this study, we test the potential for a model EDC, bisphenol A (BPA), to both initiate (via oxidative mutagenesis) and promote (via endocrine disruption) liver carcinogenesis. This study is motivated by our prior finding that developmental BPA exposure caused hepatocellular carcinoma (HCC) in mice. Here, we provide in vitro evidence supporting a mechanism for BPA as a non-genotoxic carcinogen. Using a highly sensitive, error-corrected sequencing method, we demonstrate that human population-relevant doses of BPA cause mutations that are consistent with oxidative DNA damage; however, overall mutation frequency does not differ substantially from controls. In contrast, we show that BPA inhibits cancer-protective, estrogen-induced transcription of estrogen receptor 1 (ESR1) target genes in the presence of pre-pubertal, but not post-pubertal, levels of estradiol. These results constitute strong initial evidence supporting BPA as a liver cancer promoting agent. This mechanism may be generalizable to a wide range of environmental EDCs that are weak agonists for ESR1. This finding is critically important to prevention of HCC, which is prevalent, lethal, and poorly responsive to therapy.

PMID:41497609 | PMC:PMC12767322 | DOI:10.64898/2025.12.18.695265

Comput Struct Biotechnol J. 2025 Aug 13;29:236-247. doi: 10.1016/j.csbj.2025.07.044. eCollection 2025.

ABSTRACT

As one of the endocrine-disrupting compounds (EDCs), diethylstilbestrol (DES) poses significant risks to ecosystems and human health. This study reports the development of a magnetic nanocomposite (Fe₃O₄@Al³⁺@laccase) via glutaraldehyde (GA) crosslinking to enhance DES degradation. The single factor experiments revealed that the optimum immobilization conditions were: temperature 40℃, pH 5, enzyme concentration 1.0 mg/mL, and immobilization time 1.0 h. Under these conditions, Fe₃O₄@Al³ ⁺@laccase achieved 91.71 %±2.95 % DES degradation within 12 h, as validated by HPLC, retaining 31.29 %±1.99 % of its initial catalytic activity after 10 reuse cycles. Notably, the immobilized laccase exhibited superior stability in organic solvents compared to free laccase. Fourier-transform infrared (FTIR) analysis confirmed that laccase was successfully conjugated onto Fe₃O₄@Al³ ⁺. Scanning electron microscopy and transmission electron microscopy revealed that the immobilization process preserved the original morphology and crystalline structure of Fe₃O₄@Al³ ⁺. Multi-spectroscopic analyses, including enzyme kinetics, fluorescence, and three-dimensional (3D) spectroscopy, elucidated the binding affinity and conformational changes between laccase and DES. Molecular docking simulations predicted a binding free energy of -6.4 kJ·mol⁻¹ , indicating that the conformation stability between laccase and surrounding free amino acids was mainly maintained via van der Waals, pi-pi T-shaped, Pi-Donor Hydrogen Bond, and Pi-Alkyl. This work provides proof-of-concept for using Fe₃O₄@Al³ ⁺ as a reusable magnetic support for laccase, offering a promising strategy for DES degradation and guiding the design of advanced nanomaterials for environmental bioremediation.

PMID:41497440 | PMC:PMC12765991 | DOI:10.1016/j.csbj.2025.07.044

Environ Toxicol. 2026 Jan 6. doi: 10.1002/tox.70024. Online ahead of print.

ABSTRACT

Estrogenic endocrine disrupting chemicals (EEDCs) and microplastics (MPs) are ubiquitous pollutants in aquatic systems. This study performed a bibliometric analysis, coupled with a systematic review, of 72 articles that used omics approaches to evaluate the molecular effects of these pollutants on mollusks. Cluster and co-occurrence analyses mapped research themes, and relative frequency and temporal analysis of keywords were used to identify and recommend research directions. One theme of EEDC research, involving 11 articles, addressed a controversy about whether EEDC exposure induces vitellogenin and estrogen receptor mRNA expression. An additional theme for both pollutants was induction of oxidative stress, frequently evaluated through transcriptomics in mussels. Transcriptomics was the dominant omics approach, but metabolomics is emerging. The most frequently selected EEDCs were 17α ethynylestradiol (EE2, 28%), 17β estradiol (E2, 26%), and bisphenol A (BPA, 21%). From 2006 to 2024, the most common concentration of EE2 and E2 was 0.05 μg/L, representing the high end of their environmental range. Acute and chronic exposure durations were consistently selected over time for both pollutants. The most common physical types of MPs were virgin MPs (85%) and microbeads (69%), likely due to their uniformity and availability. Only 14% of EEDC studies and 41% of MPs studies evaluated co-exposures with other chemicals, microcystein, climatic factors or pathogens. To make future studies environmentally relevant, researchers should select low concentrations, chronic exposures, aged or biodegradable plastics, and co-exposures. Thus, this study provides a basis for future environmentally relevant experimental designs.

PMID:41492704 | DOI:10.1002/tox.70024

Environ Toxicol. 2026 Jan 6. doi: 10.1002/tox.70024. Online ahead of print.

ABSTRACT

Estrogenic endocrine disrupting chemicals (EEDCs) and microplastics (MPs) are ubiquitous pollutants in aquatic systems. This study performed a bibliometric analysis, coupled with a systematic review, of 72 articles that used omics approaches to evaluate the molecular effects of these pollutants on mollusks. Cluster and co-occurrence analyses mapped research themes, and relative frequency and temporal analysis of keywords were used to identify and recommend research directions. One theme of EEDC research, involving 11 articles, addressed a controversy about whether EEDC exposure induces vitellogenin and estrogen receptor mRNA expression. An additional theme for both pollutants was induction of oxidative stress, frequently evaluated through transcriptomics in mussels. Transcriptomics was the dominant omics approach, but metabolomics is emerging. The most frequently selected EEDCs were 17α ethynylestradiol (EE2, 28%), 17β estradiol (E2, 26%), and bisphenol A (BPA, 21%). From 2006 to 2024, the most common concentration of EE2 and E2 was 0.05 μg/L, representing the high end of their environmental range. Acute and chronic exposure durations were consistently selected over time for both pollutants. The most common physical types of MPs were virgin MPs (85%) and microbeads (69%), likely due to their uniformity and availability. Only 14% of EEDC studies and 41% of MPs studies evaluated co-exposures with other chemicals, microcystein, climatic factors or pathogens. To make future studies environmentally relevant, researchers should select low concentrations, chronic exposures, aged or biodegradable plastics, and co-exposures. Thus, this study provides a basis for future environmentally relevant experimental designs.

PMID:41492704 | DOI:10.1002/tox.70024

iScience. 2025 Nov 19;28(12):114145. doi: 10.1016/j.isci.2025.114145. eCollection 2025 Dec 19.

ABSTRACT

Although per- and polyfluoroalkyl substances (PFAS) exposure has been linked to endometriosis, this association remains controversial, and the underlying mechanisms are unclear. This study aimed to investigate this relationship and explore its molecular basis. Using cross-sectional data from NHANES, we analyzed serum PFAS in 1,069 women (20-50 years), applying WQS and BKMR models to assess mixture effects. Network toxicology (protein-protein interaction, pathway enrichment), molecular docking, and external validation were also used. Results showed PFAS mixtures were positively associated with endometriosis (adjusted OR = 1.22, 95% CI: 1.08-1.39), with PFOA and PFOS as main contributors. Mechanistic analysis revealed 129 overlapping genes involved in steroid hormone signaling, inflammatory responses, and the PI3K-Akt pathway, along with potential disruptions in lipid metabolism and oxidative stress. This work provides epidemiological and mechanistic evidence that PFAS mixtures may promote endometriosis via endocrine disruption and inflammatory activation, highlighting the need for further research into their gynecological health effects.

PMID:41492385 | PMC:PMC12765064 | DOI:10.1016/j.isci.2025.114145

Environ Toxicol. 2026 Jan 6. doi: 10.1002/tox.70029. Online ahead of print.

ABSTRACT

Prostate cancer (PCa) is an endocrine-related cancer highly dependent on androgenic signaling. Beyond hormone dependence, extrinsic factors play a significant role in the risk of developing PCa, which raises concern about the influence of environmental compounds such as endocrine-disrupting chemicals (EDCs). Tributyltin (TBT) is an EDC used in antifouling paints, and its androgenic (and obesogenic) actions have been described. This study investigated the effect of TBT on various cancer hallmarks, specifically its impact on the viability, metabolism, proliferation, migration, and invasion of prostate cells, using in vitro and in vivo models. Androgen-sensitive (LNCaP) and androgen-insensitive (PC3) PCa cells were exposed to 1-100 nM TBT for 24 and 48 h. Additionally, LNCaP cells were treated with 100 nM TBT in the presence of the androgen receptor antagonist bicalutamide (1-40 μM) or 10 nM TBT and/or low-density lipoprotein (LDL, 100 μg/mL) and 5α-dihydrotestosterone (DHT, 10 nM, 48 h). Wistar rats were administered TBT (50 μg/kg) every 3 days for 45 days. TBT disrupted glycolytic flux and lipid handling in prostate cells, enhancing their proliferative activity. Moreover, 100 nM TBT stimulated migration and invasion of LNCaP cells. Bicalutamide attenuated the effect of TBT in inducing glucose consumption and LNCaP cell proliferation. A 10× lower TBT concentration maintained the stimulatory effects on LNCaP cells' viability, proliferation, and migration/invasion, sustained by high LDL-cholesterol availability and DHT. Our results show TBT as a potential inducer of PCa progression and aggressiveness and contribute to increasing awareness about the roles of EDCs in the prostate carcinogenic process.

PMID:41493038 | DOI:10.1002/tox.70029

Reprod Toxicol. 2026 Jan 3;140:109158. doi: 10.1016/j.reprotox.2026.109158. Online ahead of print.

ABSTRACT

Micro- and nanoplastics (MNPs) have been increasingly detected in human tissues, including the placenta and, more recently, the brain. Their capacity to cross biological barriers such as the placenta and the blood-brain barrier raises significant concern for sexually dimorphic neurodevelopment. Brain sexual differentiation, orchestrated by steroid hormones, neuroimmune signaling, and epigenetic programming during early life, represents one of the most hormonally sensitive and developmentally critical targets of environmental disruption. In this narrative review, we synthesize evidence positioning MNPs as potential endocrine and epigenetic disruptors that may reprogram hypothalamic circuits governing reproduction and socioemotional behavior within a DOHaD framework. Evidence is stronger in animal and cellular models, implicating oxidative stress, neuroinflammation, apoptosis, and disrupted neurotransmission as central mechanisms; however, sex-specific endpoints remain underexplored and human data are still limited. This review adds a novel integrative perspective by focusing on sexually dimorphic hypothalamic nuclei and by outlining testable, sex-informed hypotheses. We highlight key methodological priorities for future research, including environmentally relevant exposures, explicit consideration of sex as a biological variable, multi-omics approaches, and longitudinal designs.

PMID:41490752 | DOI:10.1016/j.reprotox.2026.109158

Thyroid Res. 2026 Jan 5;19(1):2. doi: 10.1186/s13044-025-00282-3.

ABSTRACT

In our review, we present possible hypotheses that might explain how sodium glucose cotransporter 2 (SGLT2) inhibitors affect thyroid function. We describe mutual interactions between thyroid hormones and the development of diabetes and obesity. We show the effects of other antihyperglycemic drugs on thyroid hormone changes. We demonstrate how endocrine-disrupting chemicals (EDCs) may act as potential triggers for the development of thyroid disease, obesity and diabetes, and how SGLT2 inhibitors may constitute a potential protective barrier against their negative effects. We describe mechanisms of the immunomodulatory and antioxidant effects of flozins, that may reduce the risk of autoimmune thyroid disease (AITD). We describe beneficial effects of flozins on heart and kidney function, that may also contribute to thyroid protection. Finally, we present a hypothesis of a possible favourable effect of SGLT2 inhibitors on Graves' orbitopathy (GO), myocardial protection in hyperthyroidism, and a reduction in the risk of thyroid cancer. Aim of our work is to summarise current evidence and hypotheses regarding SGLT2 inhibitors and thyroid function. However, it should be borne in mind that there are still limited clinical evidence about impact of flozins on thyroid metabolism.Clinical trial number Not applicable.

PMID:41491704 | PMC:PMC12772100 | DOI:10.1186/s13044-025-00282-3

Reprod Fertil Dev. 2026 Jan 6:RD25115. doi: 10.1071/RD25115. Online ahead of print.

ABSTRACT

Lysine succinylation is a recently identified post-translational modification of proteins that has been demonstrated to play critical roles in various biological activities. In recent years, research on succinylation has progressed considerably in the context of reproductive biology and associated diseases, underscoring the importance of a comprehensive review on this topic. A key mechanism underlying succinylation involves changes in the activity of succinyltransferases and desuccinylases, which in turn regulate alterations in the succinylation level of target proteins, and thereby influence multiple cellular functions. Current studies indicate that cellular succinylation levels are closely associated with both normal reproductive functions and related pathologies. For instance, elevated succinylation has been linked to impaired ovarian endocrine activity and the progression of cancers such as breast and ovarian cancer. The male reproductive system is involved in regulating spermatogenesis and has been associated with conditions including prostate and testicular cancer. Furthermore, diminished succinylation has been shown to disrupt the replacement of transition proteins in elongating spermatids and alter the distribution of germ cells within seminiferous tubules, indicating its essential role in male reproductive health. This review aims to provide a systematic overview of the fundamental characteristics of lysine succinylation and to elucidate its diverse functions within various aspects of the reproductive system, integrating recent advances to present a balanced perspective on both the physiological and pathological significance.

PMID:41490882 | DOI:10.1071/RD25115

iScience. 2025 Nov 19;28(12):114145. doi: 10.1016/j.isci.2025.114145. eCollection 2025 Dec 19.

ABSTRACT

Although per- and polyfluoroalkyl substances (PFAS) exposure has been linked to endometriosis, this association remains controversial, and the underlying mechanisms are unclear. This study aimed to investigate this relationship and explore its molecular basis. Using cross-sectional data from NHANES, we analyzed serum PFAS in 1,069 women (20-50 years), applying WQS and BKMR models to assess mixture effects. Network toxicology (protein-protein interaction, pathway enrichment), molecular docking, and external validation were also used. Results showed PFAS mixtures were positively associated with endometriosis (adjusted OR = 1.22, 95% CI: 1.08-1.39), with PFOA and PFOS as main contributors. Mechanistic analysis revealed 129 overlapping genes involved in steroid hormone signaling, inflammatory responses, and the PI3K-Akt pathway, along with potential disruptions in lipid metabolism and oxidative stress. This work provides epidemiological and mechanistic evidence that PFAS mixtures may promote endometriosis via endocrine disruption and inflammatory activation, highlighting the need for further research into their gynecological health effects.

PMID:41492385 | PMC:PMC12765064 | DOI:10.1016/j.isci.2025.114145

Endocrine. 2026 Jan 6;91(1):32. doi: 10.1007/s12020-025-04521-3.

ABSTRACT

Various types of external chemicals can disrupt the endocrine system, interfering with normal hormone function and causing a broad spectrum of negative health effects. Endocrine-disrupting chemicals (EDCs) are a diverse group of natural and synthetic chemicals that are known to contaminate the environment. It is postulated that these agents can contribute to the development of many diseases, including infertility and cancer, because of their ability to interfere with estrogen receptors (ERs). Bisphenols (BPs) are a group of compounds that belong to EDCs, the most common of which is bisphenol A (BPA). Due to restrictions on the use of BPA in industry, analogues such as bisphenol S (BPS) and bisphenol F (BPF) have been introduced. However, some reports indicate that BPA analogues also have negative effects on the endocrine system in both humans and animals because of their structural similarity. This review summarises current knowledge related to BPA, its analogues and their role in female infertility and hormone-related cancers. Furthermore, this review also points to the problem of exposure to more than one estrogenic agent and highlights the importance of considering exposure to multiple chemicals when assessing health effects and setting daily limits.

PMID:41493512 | PMC:PMC12775122 | DOI:10.1007/s12020-025-04521-3

Turk J Med Sci. 2025 Oct 26;55(7):1602-1612. doi: 10.55730/1300-0144.6120. eCollection 2025.

ABSTRACT

The global prevalence of obesity and metabolic syndrome (MetS) is rising worldwide, and increasing evidence suggests that chemical exposures-particularly endocrine disruptors (EDs)-represent a significant contributing factor. EDs can act as obesogens, increasing the risk of weight gain and related metabolic conditions, including type 2 diabetes, dyslipidemia, hypertension, and cardiovascular disease. They may also alter the basal metabolic rate, gut microbiota composition, and hormonal regulation of appetite and satiety. EDs are reported to exert their effects mainly through the peroxisome proliferator-activated receptor gamma pathway, which is primarily expressed in adipose tissue and is a key regulator of adipogenesis. Common consumer products such as plastic bottles, metal food cans, detergents, toys, cosmetics, and pesticides frequently contain EDs. Humans can be exposed to these chemicals via multiple routes, including transplacental transfer, breast milk, inhalation, ingestion, and dermal absorption. Bisphenols, tributyltin, phthalates, per- and polyfluoroalkyl substances, polycyclic aromatic hydrocarbons, and heavy metals are among the known EDs that have been associated with obesity and MetS. The need for further investigation and stricter regulations to mitigate the public health consequences of environmental exposure to EDs is consistently emphasized in recent literature. Understanding the mechanisms by which EDs affect various hormones and systems is essential for developing effective prevention and intervention strategies. In this review, we discuss the relationship between obesity, MetS, and EDs, along with exposure pathways and preventive strategies.

PMID:41488238 | PMC:PMC12758928 | DOI:10.55730/1300-0144.6120

J Endocr Soc. 2025 Dec 12;10(1):bvaf208. doi: 10.1210/jendso/bvaf208. eCollection 2026 Jan.

ABSTRACT

CONTEXT: Hypospadias is a common malformation, which can be caused by a disruption of hormone signaling during development. Endocrine disrupting chemicals (EDCs) cross the placenta and can interfere with hormone synthesis and metabolism.

OBJECTIVE: To evaluate whether intrauterine exposure to environmental phenols and/or parabens is associated with hypospadias.

METHODS: This was a case-control pilot study of term infant males with (n = 6) and without (n = 16) hypospadias. Meconium was tested for bisphenol-A (BPA), bisphenol-S (BPS), bisphenol-F (BPF), methylparaben (MePb), and propylparaben (PrPb) using a novel lab procedure.

RESULTS: BPA concentrations were higher in cases vs controls, though this difference was not statistically significant. Higher meconium concentration of BPA was associated with shorter Anogenital distance (AGD); higher BPS and BPA were associated with shorter stretched penile length (SPL). There were no significant differences for BPS, BPF, MePb, or PrPb.

CONCLUSION: This study demonstrated that EDCs were present in meconium samples, supporting the hypothesis that maternal exposure results in fetal exposure during a time of critical fetal urogenital development. Our data suggests a pattern of higher BPA in cases of hypospadias compared to controls while BPA and BPS were inversely related to AGD and SPL. However, the study is limited by small sample size and therefore was underpowered to detect conclusive differences between the 2 groups. Further studies in EDC exposure and genitourinary differences are warranted.

PMID:41488028 | PMC:PMC12757584 | DOI:10.1210/jendso/bvaf208

Turk J Med Sci. 2025 Oct 13;55(7):1613-1619. doi: 10.55730/1300-0144.6121. eCollection 2025.

ABSTRACT

Endocrine disrupting chemicals (EDCs) are exogenous compounds that have hormone-like effects inside the body. Endocrine disruptors can affect adrenal glands in humans and animals. Adrenocortical dysfunction related to chemical exposure has been reported in the literature. The human adrenal gland is crucial for the synthesis of steroid hormones (glucocorticoids, mineralocorticoids, and androgens) and amino acid-derived hormones (epinephrine and norepinephrine). All steps in the adrenocortical steroidogenesis pathway are potential targets for chemical inhibition, including the adrenocorticotropic hormone receptor, steroidogenic acute regulatory protein, mitochondrial cytochrome P450 (CYP) enzymes (CYP11A1, CYP17, CYP21, CYP11B1, and CYP11B2), and 3-hydroxysteroid dehydrogenase D4,5 isomerase. EDCs either inhibit the enzymes in steroid biosynthesis or, occasionally, activate them further. Several studies have reported evidence linking EDC exposure to different cancers, early puberty, and reproductive dysfunction. The risk of these harmful effects is higher during development. Pregnant women, babies, children, and adolescents are especially vulnerable, and should therefore be kept away from these chemicals.

PMID:41488240 | PMC:PMC12758923 | DOI:10.55730/1300-0144.6121

Turk J Med Sci. 2025 Oct 26;55(7):1595-1601. doi: 10.55730/1300-0144.6119. eCollection 2025.

ABSTRACT

Endocrine-disrupting chemicals (EDCs) are compounds that interfere with hormone synthesis, secretion, metabolism, or excretion. Evidence indicates that increased exposure to EDCs is associated with insulin resistance and, most notably, type 2 diabetes worldwide. This suggests a diabetogenic effect that is independent of obesity, underscoring the complex mechanisms and broad impact of EDCs on metabolic health. Key pathways include hormone mimicry and antagonism, altered hormone metabolism, inflammatory responses, and mitochondrial dysfunction. This review summarises the mechanisms through which EDCs contribute to these conditions and evaluates the epidemiological and experimental evidence supporting these associations.

PMID:41488239 | PMC:PMC12758926 | DOI:10.55730/1300-0144.6119

Turk J Med Sci. 2025 Oct 26;55(7):1620-1624. doi: 10.55730/1300-0144.6122. eCollection 2025.

ABSTRACT

Fetal development depends on complex maternal-fetal-placental interactions, with thyroid hormones playing a vital role in regulating growth and neurogenesis. Exposure to endocrine-disrupting chemicals (EDCs) during pregnancy has emerged as a significant risk factor for thyroid dysfunction and its associated developmental and cognitive disorders. EDCs, including bisphenol A (BPA), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), perfluoroalkyl substances, pesticides, and heavy metals, disrupt thyroid hormone synthesis, secretion, and metabolism. Mechanisms involve receptor binding, disruption of the hypothalamic-pituitary-thyroid axis, and inhibition of thyroid peroxidase activity. BPA exposure, for instance, reduces free and total T4 levels and interferes with deiodinase activity. Similarly, PCBs and PBDEs are associated with lower thyroxine concentrations and long-term behavioral abnormalities in offspring. Pesticides and heavy metals exacerbate thyroid dysfunction by interfering with hormone synthesis and receptor interactions. Genetic predisposition, iodine deficiency, and autoimmune conditions further increase susceptibility to EDC-related thyroid disorders. Considering the heightened vulnerability of early pregnancy and the widespread environmental presence of EDCs, reducing exposure and implementing regulatory measures are essential to mitigate their adverse effects on maternal and fetal thyroid health. Future research should prioritize elucidating the mechanisms of EDC-induced thyroid dysfunction and developing interventions to protect at-risk populations.

PMID:41488242 | PMC:PMC12758918 | DOI:10.55730/1300-0144.6122

Turk J Med Sci. 2025 Oct 13;55(7):1635-1640. doi: 10.55730/1300-0144.6124. eCollection 2025.

ABSTRACT

Endocrine disruptors (EDs) are closely associated with the second brain, the microbiota-derived enteric nervous system, commonly referred to as the gut microbiota. The microbiota plays a crucial role in human health and the development of diseases. In today's industrialized world, the presence of EDs in air, water, and soil leads to primary human exposure through dermal contact and ingestion. The impact of these EDs on the microbiota remains unclear. EDs that disrupt the balance of the gut microbiota may contribute to a range of disorders, including metabolic (obesity, diabetes mellitus), cardiovascular (vascular stenosis, cerebrovascular disease), reproductive (infertility, ovarian and testicular tumors), neurological (dysfunction of the amygdala, cortex, and cerebellum), and behavioral disorders (dementia, depression, anxiety, and schizophrenia). This review examines the effects of commonly encountered environmental EDs on the gut microbiota and summarizes the most recent findings on this topic. The concept of the microbiota-derived enteric nervous system and the modulation of the hormonal system through interactions between microorganisms and environmental chemicals have prompted specialists in endocrinology and metabolism to reconsider patient management and treatment strategies. This necessitates a comprehensive evaluation of treatment options that incorporate microbiome data. The information presented in this review will help illuminate future research directions and serve as a valuable resource for subsequent studies.

PMID:41488241 | PMC:PMC12758922 | DOI:10.55730/1300-0144.6124

Turk J Med Sci. 2025 Dec 26;55(7):1664-1670. doi: 10.55730/1300-0144.6128. eCollection 2025.

ABSTRACT

Endocrine disruptors are chemical substances widely utilized across various industrial sectors. Due to their structural similarity to natural ligands, they bind to receptors and influence the endocrine system via agonist-antagonist mechanisms. Exposure occurs through the consumption of contaminated food and water, inhalation of polluted air and dust, and dermal contact. Owing to their dynamic remodeling capacity, bones represent potential targets for endocrine-disrupting chemicals. These chemicals can disrupt bone formation, skeletal development, hormonal regulation, and calcium metabolism. Sensitivity to endocrine-disrupting chemicals is greatest during the prenatal and early postnatal periods. This review summarizes the effects of endocrine-disrupting chemicals on bone tissue.

PMID:41488244 | PMC:PMC12758924 | DOI:10.55730/1300-0144.6128

Turk J Med Sci. 2025 Nov 26;55(7):1625-1634. doi: 10.55730/1300-0144.6123. eCollection 2025.

ABSTRACT

BACKGROUND/AIM: Sensitivity to endocrine disruptors is higher in early life. Endocrine disruptor chemicals can be passed from pregnant women to their babies through the placenta or breast milk during lactation, leading to long-term and potentially permanent adverse effects.

MATERIALS AND METHODS: This review evaluates the effects of endocrine-disrupting chemicals (EDCs) on pregnancy by summarizing findings from experimental and observational studies. Exposure routes, reproductive outcomes, fetal development implications, and potential preventive strategies are analyzed.

RESULTS: Exposure to EDCs during pregnancy has been linked to various complications, including infertility, implantation defects, premature birth, spontaneous abortions, gestational hypertension, and gestational diabetes. Intrauterine exposure to these chemicals may lead to metabolic disorders, congenital anomalies, low birth weight, and delayed physical and mental development in offspring depending on the level and timing of exposure.

CONCLUSION: Due to the significant impact of endocrine disruptors on maternal and fetal health, it is critical to implement protective measures to reduce exposure during pregnancy and lactation. Increased awareness and preventive strategies can help mitigate adverse effects.

PMID:41488243 | PMC:PMC12758921 | DOI:10.55730/1300-0144.6123

J Biol Rhythms. 2026 Jan 4:7487304251386926. doi: 10.1177/07487304251386926. Online ahead of print.

ABSTRACT

Circadian clocks present throughout the brain and body coordinate diverse physiological processes to support daily homeostasis, yet the specific interorgan signaling axes involved are not well defined. We previously demonstrated that the skeletal muscle clock controls transcript oscillations of genes involved in fatty acid metabolism in the liver, yet the impact of the liver clock on the muscle remained unknown. Here, we use male hepatocyte-specific Bmal1 KO mice (Bmal1^hep-/-) to reveal that approximately one-third of transcript rhythms in skeletal muscle are influenced by the liver clock in vivo. Treatment of myotubes with serum harvested from Bmal1^hep-/- mice inhibits expression of genes involved in metabolic pathways, including oxidative phosphorylation. Only small transcriptional changes were induced by liver clock-driven endocrine communication in vitro, leading us to surmise that the liver clock acts to fine-tune metabolic gene expression in muscle. Consistent with functional tuning, treatment of myotubes with serum collected from Bmal1^hep-/- mice during the dark phase lowers mitochondrial ATP production compared with serum from wild-type mice. Overall, our results reveal communication between the liver clock and skeletal muscle, uncovering a bidirectional endocrine communication pathway that may contribute to the metabolic phenotypes of circadian disruption.

PMID:41486525 | PMC:PMC12774450 | DOI:10.1177/07487304251386926

Turk J Med Sci. 2025 Nov 6;55(7):1671-1680. doi: 10.55730/1300-0144.6129. eCollection 2025.

ABSTRACT

Endocrine-disrupting chemicals (EDCs) are environmental contaminants that disrupt hormonal regulation by mimicking, inhibiting, or modifying endocrine signaling pathways. EDCs are commonly present in plastics, pesticides, industrial byproducts, and personal care products and pose substantial health risks, particularly to vulnerable groups such as infants and children. Early-life exposure is especially concerning due to the developing detoxification systems, the immaturity of the blood-brain barrier, and the ongoing organ differentiation, making these periods highly susceptible to EDCs' harmful effects. Moreover, exposure during critical developmental periods, such as sex differentiation and neurodevelopment, can lead to significant long-term developmental impairments that persist into later life. Perinatal and childhood exposure to EDCs has been linked to various adverse health outcomes, including neurodevelopmental delays, impairments in reproductive health, obesity, type 2 diabetes, thyroid dysfunction, and even a heightened risk of certain malignancies. These effects are mediated through various mechanisms, including direct modulation of hormone receptors, disruption of genetic regulation, and interference with endocrine feedback systems. Alterations in endocrine signaling, particularly disruptions in thyroid hormone homeostasis, may also indirectly impair cognitive development, increasing the risk of attention disorders and intellectual impairment. Although regulatory measures to reduce EDC exposure are crucial, current restrictions remain insufficient. Moreover, as new EDCs emerge, ongoing research is essential to understand their risks and develop effective strategies to minimize their potential harm. Protecting future generations requires a proactive approach that combines public health awareness, strong regulations, and ongoing scientific research. This review highlights the potential risks of EDCs exposure in children and highlights the significance of multidisciplinary research and policy efforts.

PMID:41488246 | PMC:PMC12758920 | DOI:10.55730/1300-0144.6129

Turk J Med Sci. 2025 Oct 26;55(7):1648-1656. doi: 10.55730/1300-0144.6126. eCollection 2025.

ABSTRACT

Environmental endocrine-disrupting chemicals (EDCs) have emerged as a critical global health concern because of their role in various diseases, including thyroid cancer. Defined as exogenous substances that disrupt endocrine system functions, EDCs can affect multiple generations through mechanisms such as hormone receptor modulation, altered hormone synthesis, and epigenetic modifications. The increasing global incidence of thyroid cancer has heightened interest in environmental factors, with EDC exposure recognized as a significant contributor. Compounds such as heavy metals, persistent organic pollutants, per- and polyfluoroalkyl substances, and bisphenol A play crucial roles in disrupting thyroid homeostasis. Emerging evidence underscores the synergistic effects of multiple EDC exposures, further amplifying cancer risk. This review explores the relationship between EDC exposure and thyroid carcinogenesis, focusing on key chemical compounds and their mechanisms of action. Understanding these links is essential for guiding public health policies and shaping future research aimed at preventing and improving the management of this malignancy.

PMID:41488247 | PMC:PMC12758927 | DOI:10.55730/1300-0144.6126

Turk J Med Sci. 2025 Oct 9;55(7):1641-1647. doi: 10.55730/1300-0144.6125. eCollection 2025.

ABSTRACT

Endocrine-disrupting chemicals (EDCs) are a diverse, comprehensive group of mostly synthetic chemicals that disrupt many physiological functions in humans and animals. EDCs are particularly disruptive to the female reproductive system. Reproductive function in women is a dynamic process regulated by the hypothalamic-pituitary-ovarian axis. EDCs show their effects on the reproductive system through estrogenic, antiestrogenic, androgenic, and antiandrogenic effects or by directly affecting gonadotropin-releasing hormone secretion. Disruption in the menstrual cycle, decrease in fertility, infertility, increased risk of miscarriage, polycystic ovary syndrome, endometriosis, early or delayed puberty, and hormone-sensitive cancers can be listed as the main negative effects of endocrine disruptors on the female reproductive system. In this review, findings on the effects of the most studied EDCs, bisphenol A, phthalates, methoxychlor ethane, tetrachlorodibenzo-p-dioxin, atrazine, per- and polyfluoroalkyl substances, and micro- and nanoplastics on the female reproductive system are summarized.

PMID:41488248 | PMC:PMC12758919 | DOI:10.55730/1300-0144.6125

Turk J Med Sci. 2025 Oct 9;55(7):1641-1647. doi: 10.55730/1300-0144.6125. eCollection 2025.

ABSTRACT

Endocrine-disrupting chemicals (EDCs) are a diverse, comprehensive group of mostly synthetic chemicals that disrupt many physiological functions in humans and animals. EDCs are particularly disruptive to the female reproductive system. Reproductive function in women is a dynamic process regulated by the hypothalamic-pituitary-ovarian axis. EDCs show their effects on the reproductive system through estrogenic, antiestrogenic, androgenic, and antiandrogenic effects or by directly affecting gonadotropin-releasing hormone secretion. Disruption in the menstrual cycle, decrease in fertility, infertility, increased risk of miscarriage, polycystic ovary syndrome, endometriosis, early or delayed puberty, and hormone-sensitive cancers can be listed as the main negative effects of endocrine disruptors on the female reproductive system. In this review, findings on the effects of the most studied EDCs, bisphenol A, phthalates, methoxychlor ethane, tetrachlorodibenzo-p-dioxin, atrazine, per- and polyfluoroalkyl substances, and micro- and nanoplastics on the female reproductive system are summarized.

PMID:41488248 | PMC:PMC12758919 | DOI:10.55730/1300-0144.6125

Turk J Med Sci. 2025 Nov 11;55(7):1657-1663. doi: 10.55730/1300-0144.6127. eCollection 2025.

ABSTRACT

BACKGROUND/AIM: There is increasing interest in endocrine disrupting chemicals because of the potential effects on neurological health. These chemicals are widely found in various consumer products and industrial processes, and can lead to serious disorders of the endocrine system by disrupting hormone synthesis, expression, and function. The aim of this review was to examine epidemiological and experimental findings by investigating the link between exposure to endocrine disrupting chemicals and adverse neurological outcomes.

MATERIALS AND METHODS: In the preparation of this review, a PubMed literature search was conducted using the words "endocrine disruptors," "neuroendocrine effects," "neurobehavioral effects," and "neurodevelopmental effects" and articles containing relevant studies were examined.

RESULTS: Recent studies have shown a strong correlation between exposure to endocrine disrupting chemicals and the development of neurodegenerative diseases such as Alzheimer's and Parkinson's disease, and neurodevelopmental diseases such as autism spectrum disorder and attention deficit hyperactivity disorder. The effects of common pollutants such as pesticides, bisphenol A, polychlorinated biphenyls, and heavy metals on the endocrine system have been especially emphasized.

CONCLUSION: In conclusion, understanding the role played by endocrine disrupting chemicals in the development of neurological diseases will be of critical importance in the development of new strategies to prevent these diseases.

PMID:41488245 | PMC:PMC12758925 | DOI:10.55730/1300-0144.6127

J Natl Cancer Inst. 2026 Jan 2:djaf376. doi: 10.1093/jnci/djaf376. Online ahead of print.

ABSTRACT

BACKGROUND: Testicular germ cell tumors (TGCT) are thought to be endocrine-related. The hypothesis, however, has not been thoroughly investigated. As a result, pre-diagnostic serum samples from the U.S. Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) were analyzed to assess the relationship of hormones and gonadotropins to TGCT risk.

METHODS: The study included 517 men who subsequently developed TGCT and 790 comparison men. The hormones/gonadotropins examined included testosterone, estradiol, sex-hormone binding globulin (SHBG), 5α-androstane-3α,17β-diol glucuronide (3α-diol G), follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression. Analyses stratified by histology (seminoma, nonseminoma) were also conducted.

RESULTS: Compared to men in the middle quintile of LH concentrations, men with the lowest concentrations had an increased risk of TGCT (OR 1.88, 95% CI 1.31-2.70), as did men with FSH concentrations in the lowest (OR 1.77, 95% CI 1.21-2.60) and highest quintiles (OR 2.20, 95% CI 1.53-3.17). An increased risk of seminoma was found with both low and high LH, and high FSH, while an increased risk of nonseminoma was found with low LH, and both low and high FSH. Decreased levels of 3α-diol G were associated with increased risk of seminoma (OR 1.65, 95%CI 1.02-2.67).

CONCLUSION: These results suggest that gonadotropin disruption may be a critical event in the development of TGCT. Further examination of upstream and downstream metabolites in the hormone pathways may help elucidate the underlying mechanism that distinguishes men who develop TGCT from men who do not.

PMID:41485106 | DOI:10.1093/jnci/djaf376

Aquat Toxicol. 2025 Dec 29;291:107699. doi: 10.1016/j.aquatox.2025.107699. Online ahead of print.

ABSTRACT

Juvenile hormone analogs (JHAs) are widely used insect growth regulators that disrupt endocrine signaling and impair reproduction in arthropods. Although their effects on non-target crustaceans such as Daphnia magna are well documented, the cellular mechanisms underlying JHA-induced reproductive toxicity remain unclear. In this study, we performed time-course exposure experiments to identify the sensitive window during which fenoxycarb reduces fecundity and investigated the associated ovarian changes. We generated a germline-specific VASA:H2B-GFP knock-in line to visualize ovarian nuclei in vivo and found that exposure during 16-32 h after oviposition resulted in marked reductions in offspring number. High-resolution fluorescence and multiphoton imaging revealed apoptosis-like nuclear abnormalities in developing oocytes, indicating that oocyte degeneration contributes to reduced fecundity. This study provides evidence that oocyte degeneration contributes to fenoxycarb-induced reproductive impairment and highlights the utility of genetic and live-imaging tools for advancing mechanistic understanding of endocrine disruption in small aquatic invertebrates.

PMID:41485427 | DOI:10.1016/j.aquatox.2025.107699

Noise Health. 2025 Nov-Dec 01;27(129):641-652. doi: 10.4103/nah.nah_183_25. Epub 2025 Dec 31.

ABSTRACT

OBJECTIVES: This review examines how nighttime noise and irregular schedules influence circadian and endocrine regulation. It introduces a conceptual multilevel model to explore how these exposures may accumulate over time and contribute to long-term health risks.

METHODS: A scoping narrative review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses principles in PubMed, Scopus, Web of Science and Embase (1992-2024), including human studies on nighttime noise and shift work. Eligible studies involved adults and reported circadian, hormonal, metabolic or chronic disease outcomes. Twenty-five studies were synthesised using direction-based vote counting due to heterogeneity because meta-analysis was not feasible. The tally reflected the direction of effects rather than statistical significance. Risk-of-bias assessments informed interpretation, but not exclusion. Findings were integrated into a multilevel model integrating exposure, physiological mediation and cumulative effects.

RESULTS: Nighttime noise and rotating night duties shifted melatonin timing and reduced sleep continuity. Studies reported increased fasting glucose, decreased insulin sensitivity and unfavourable lipid profiles in groups exposed to these work periods. Several investigations described an increase in cardiometabolic load amongst long-term night-duty workers. In the simulation scenarios, the model followed these findings and produced circadian and metabolic changes that increased across repeated exposure cycles.

CONCLUSIONS: This review proposes and illustrates a dynamic framework for understanding how nighttime noise and shift work may contribute to circadian and metabolic disruption over time. Its exploratory nature reflects heterogeneous evidence and a scoping design. The findings should be interpreted without causal inference.

PMID:41482893 | DOI:10.4103/nah.nah_183_25

Ecotoxicology. 2026 Jan 3;35(2):29. doi: 10.1007/s10646-025-03007-2.

NO ABSTRACT

PMID:41483019 | DOI:10.1007/s10646-025-03007-2

Environ Pollut. 2026 Jan 1;392:127628. doi: 10.1016/j.envpol.2025.127628. Online ahead of print.

ABSTRACT

OBJECTIVE: Di-(2-ethylhexyl) phthalate (DEHP), a ubiquitous plasticizer of significant health concern due to its endocrine disrupting effects. The study aims to elucidate underlying molecular mechanisms between DEHP exposure and prostate cancer (PCa).

METHODS: In vitro and in vivo experiments were undertaken to validate the effects of DEHP on the biological function of prostate cancer, and RNA sequencing was performed to elucidate the underlying mechanism. We integrated in silico toxicological assessments and bioinformatics methodologies was employed to investigate the key targets and associated downstream pathways in DEHP-induced PCa progression.

RESULTS: In vitro and in vivo experiments showed that MEHP promoted the proliferation, migration, and invasion of PCa cells and tumorigenicity, and RNA sequencing revealed that the metabolic pathways, pathways in cancer, PI3K-Akt signaling pathway, MAPK signaling pathway might be potential mechanisms involved in this process. Additionally, six DEHP-related genes were identified and a DEHP-related model was constructed. The data of scRNA indicated that these six DEHP-related genes may contribute in the tumor microenvironment of PCa. The molecular docking analysis revealed DEHP's ability to bind to crucial DEHP -related proteins.

CONCLUSIONS: Our study unveils a novel insight into the function for DEHP in PCa, shedding new light on prediction, assessment, and mitigation of DEHP exposure and PCa progression.

PMID:41483848 | DOI:10.1016/j.envpol.2025.127628

Neuroprotection. 2025 Sep 15;3(4):386-395. doi: 10.1002/nep3.70015. eCollection 2025 Dec.

ABSTRACT

Postoperative delirium (POD), a prevalent neurological complication in older surgical patients, adversely affects recovery. Isoflurane, a common inhalational anesthetic, exhibits neurotoxic potential, but its role in POD pathogenesis remains unclear. Network toxicology and molecular docking strategies identified 38 shared targets between isoflurane (PubChem/ChEMBL) and POD (GeneCards). Protein-protein interaction networks (STRING/Cytoscape) screened eight core genes: catechol-O-methyltransferase (COMT), angiotensin l-converting enzyme (ACE), solute carrier family 6, member 3 (SLC6A3), cathepsin B (CTSB), apoptosis-related cysteine peptidase (CASP3), B-lymphoblastoma-2 gene (BCL-2), coagulation factor VII (F7), and nuclear receptor subfamily 3 (NR3C1). Functional enrichment (Gene Ontology [GO]/Kyoto Encyclopedia of Genes and Genomes [KEGG]) analyzed biological pathways. Key pathways implicated include calcium signaling, dopamine/catecholamine synaptic uptake, cholinergic synapses, endocrine resistance, and estrogen signaling. Molecular docking confirmed strong binding affinity between isoflurane and core targets (e.g., CASP3: affinity-5.54 kcal/mol), highlighting dopaminergic disruption and apoptotic activation. This study elucidates isoflurane's multi-target neurotoxicity in POD, providing a mechanistic foundation for mitigating postoperative neurological complications.

PMID:41479770 | PMC:PMC12754565 | DOI:10.1002/nep3.70015

Front Public Health. 2025 Dec 17;13:1633266. doi: 10.3389/fpubh.2025.1633266. eCollection 2025.

ABSTRACT

INTRODUCTION: Health behaviors and exposures to environmental hazards among individuals of reproductive age prior to pregnancy can influence maternal and child health outcomes. While research attention has focused on preconception health behaviors, such as diet and lifestyle, there is emerging evidence that environmental exposures may also be important to consider.

METHODS: A search strategy (PROSPERO # CRD42021240069) was developed for MEDLINE (OVID), EMBASE (OVID), Maternity and Infant Care (OVID), CINAHL (EBSCO), and PsycINFO (EBSCO). Searches were conducted from database inception until 21 May 2021. Studies were included that investigated male or female exposure to any environmental hazard during the preconception period and reported neonatal or child health outcomes. No limit to date of publication, language or comparator were applied. Studies were critically appraised using the Newcastle-Ottawa Quality Assessment Scale for Cohort studies.

RESULTS: The review identified 63 studies that met the inclusion criteria, published between 1974 and 2021. They encompassed studies that covered ambient exposures (n = 23), chemical exposures (n = 26), and other exposures (n = 24). For ambient exposures, all studies examined the outcomes associated with air pollution and one study also explored associations with exposure to hot and cold ambient temperature. Studies investigating chemical exposures encompassed endocrine-disrupting chemicals (n = 4), pesticides (n = 10), persistent organic pollutants (n = 4), and organic solvents (n = 7). Other exposures studied were categorized as radiation (n = 9), metals (n = 4) and undifferentiated products or compounds (n = 14). Outcomes measured by the included studies covered congenital malformations, adverse birth outcomes and childhood illness. There was a high level of heterogeneity across the included studies that precluded meta-analysis. Various associations between exposures and outcomes were identified.

DISCUSSION: There is growing evidence of adverse outcomes in offspring associated with maternal and paternal environmental exposures during the pre-conception period. While there are some topics that have received focused attention from research teams in the last 50 years, most studies appear to be standalone and have not continued to develop as part of wider research programs. There is need to develop a field-wide approach to create an agenda for environmental preconception health exposures and outcomes that supports more coordinated, targeted and strategic research efforts.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD42021240069.

PMID:41480069 | PMC:PMC12753933 | DOI:10.3389/fpubh.2025.1633266

Front Endocrinol (Lausanne). 2025 Dec 17;16:1717675. doi: 10.3389/fendo.2025.1717675. eCollection 2025.

ABSTRACT

Inborn metabolic diseases (IMDs) represent a diverse and complex group of rare disorders, typically resulting from variants in genes that encode specific enzymes or cofactors, leading to reduced or absent enzymatic activity. These conditions commonly disrupt one or more metabolic pathways, often impacting multiple organ systems from early childhood. Clinicians should consider the possibility of an IMD when an endocrine abnormality is accompanied by other unexplained clinical signs or in presence of combined endocrinopathies. While some IMDs associated with endocrine dysfunction in children and adolescents are well-documented and supported by established treatment guidelines, others lack clear recommendations or are characterized by inconsistent data. This narrative review aims to summarize the main IMDs that present with endocrine abnormalities in pediatric patients, organized according to affected organ systems and underlying pathophysiological mechanisms. Furthermore, we reviewed the latest recommendations, when available, for monitoring endocrine function in children with these disorders and eventually for providing a tailored treatment, where applicable.

PMID:41480351 | PMC:PMC12753368 | DOI:10.3389/fendo.2025.1717675

J Steroid Biochem Mol Biol. 2025 Dec 31;257:106927. doi: 10.1016/j.jsbmb.2025.106927. Online ahead of print.

ABSTRACT

Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder in women of reproductive age, markedly impairing their health and reducing overall quality of life. Vitexin is a natural flavonoid compound that has demonstrated diverse pharmacological properties, including anti-inflammatory and antioxidant effects. The aim of this study was to investigate the effects of vitexin on dihydrotestosterone (DHT)-induced fibrosis in KGN cells, as well as its regulatory role in the NR4A1/NLRP3 signaling pathway. Experimental findings suggested that DHT treatment resulted in decreased cell viability, disrupted sex hormone balance, increased oxidative stress, and elevated levels of inflammation and fibrosis in KGN cells. However, vitexin intervention significantly reversed these pathological changes. Transcriptomics sequencing analysis and molecular docking further indicated that NR4A1 is a pivotal target of vitexin in modulating the inflammatory response. Vitexin significantly inhibited NLRP3 inflammasome-mediated inflammation by activating NR4A1, conversely NR4A1 knockdown partially attenuated the protective effects of vitexin (P < 0.01). Therefore, vitexin was found to effectively ameliorate DHT-induced alterations in cell viability, sex hormone levels, oxidative stress, inflammation and fibrosis in KGN cells. These protective effects appear to be closely related to the regulation of the NR4A1/NLRP3 signaling pathway.

PMID:41482075 | DOI:10.1016/j.jsbmb.2025.106927

Toxicology. 2025 Dec 31;521:154393. doi: 10.1016/j.tox.2025.154393. Online ahead of print.

ABSTRACT

Bisphenol A (BPA) and its structural analogues are widely used in plastics production, raising concern due to endocrine-disrupting properties. While many analogues share structural similarities with BPA, their endocrine-disrupting effects remain insufficiently characterized. Cyclo-di-bisphenol A diglycidyl ether (cyclo-di-BADGE), tetrabromobisphenol S (TBBPS), bisphenol SIP (BPSIP), and bisphenol TMC (BPTMC) are particularly understudied. We assessed the estrogenic activity of these four BPA analogues compared to BPA. Transactivation assays in HEK-293 cells expressing estrogen receptor alpha (ERα) revealed that BPTMC was a more potent ERα agonist than BPA, with an EC₅₀ of 87 ± 20 nM versus 400 ± 100 nM for BPA, while the other tested analogues showed no significant agonistic activity. In silico analysis attributed this higher affinity to greater hydrophobicity and a bulkier bridging group between its phenolic rings. None of the compounds inhibited 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) activity. However, BPTMC selectively inhibited 17β-HSD2 (IC₅₀ = 4.8 ± 0.6 µM) but not BPA. Importantly, 24 h exposure of ERα-positive MCF-7 breast cancer cells to 1 µM BPTMC upregulated the expression of the ERα target genes GREB1, TFF1, and PGR, comparable to 10 nM E2, which was abolished by 100 nM of the ERα antagonist fulvestrant. Moreover, BPTMC stimulated MCF-7 cell proliferation at nanomolar concentrations over 72 h, and cell count analyses confirmed this effect. BPA also increased cell numbers, and both effects were reversed by fulvestrant. Collectively, we identified BPTMC as a potent ERα agonist capable of eliciting transcriptional and mitogenic responses at low concentrations, raising concerns about its endocrine-disrupting and breast cancer-promoting effects.

PMID:41482203 | DOI:10.1016/j.tox.2025.154393

Front Endocrinol (Lausanne). 2025 Dec 16;16:1731179. doi: 10.3389/fendo.2025.1731179. eCollection 2025.

ABSTRACT

Polycystic ovary syndrome (PCOS) is the most common endocrine-metabolic disorder in reproductive-age women, characterized by hyperandrogenism (HA) and insulin resistance (IR). Despite its high prevalence, the underlying pathophysiology remains incompletely understood. In recent years, bidirectional interactions between androgens and adipose tissue (AT) have been recognized as a key driver of the vicious cycle in PCOS. This review systematically examines this core interaction mechanism: on one hand, dysfunctional AT (particularly visceral fat) exacerbates ovarian androgen overproduction by intensifying IR, inducing chronic low-grade inflammation (e.g., elevated TNF-α and IL-6), and reducing adiponectin levels. Conversely, HÀ exacerbates AT dysfunction and systemic IR by altering body fat distribution (central obesity), suppressing lipogenesis, impairing lipolysis, and disrupting adipokine secretion (e.g., reduced adiponectin, elevated leptin). This bidirectional positive feedback loop within the fat-androgen axis perpetuates the worsening metabolic and reproductive abnormalities in PCOS. Based on this mechanism, existing therapeutic strategies-including lifestyle interventions, insulin sensitizers (e.g., metformin), GLP-1 receptor agonists, and anti-androgens-partially exert their effects by improving AT function and antagonizing androgenic effects. Emerging therapies such as SGLT-2 inhibitors, BAT transplantation, anti-TNF-α therapies, and gut microbiota targeting offer promising new avenues for directly intervening in this axis and breaking the vicious cycle of PCOS. A deeper understanding of fat-androgen interactions is crucial for developing precision treatments for PCOS.

PMID:41476920 | PMC:PMC12747969 | DOI:10.3389/fendo.2025.1731179

Med Rev (2021). 2025 Dec 19;5(6):452-476. doi: 10.1515/mr-2025-0039. eCollection 2025 Dec.

ABSTRACT

Gastrointestinal (GI) complications are prevalent and severe clinical challenges encountered in critically ill patients. They are closely linked to disease progression, increased morbidity and mortality, and escalating healthcare expenses. This comprehensive review summarizes the epidemiology of GI complications in critically ill patients, elucidating the underlying pathophysiological mechanisms including hemodynamic alterations, inflammatory cascades, neuro-endocrine dysregulation, and gut microbiota imbalance. It confers distinctive clinical manifestations and effective diagnostic approaches. Therapeutic strategies, encompassing nutritional support, pharmacological management, and surgical or interventional procedures will be discussed. The review also briefly introduces the concept of the "gut-organ axis," emphasizing how intestinal barrier disruption and dysbiosis can disseminate inflammatory and metabolic signals to distant organs such as the lungs, liver, kidneys, and brain, thereby underscoring the need for clinicians to recognize systemic effects. In essence, prompt identification and multimodal intervention are pivotal for optimizing outcomes in critically ill patients; judiciously addressing GI complications in clinical decision-making can mitigate morbidity and enhance both short-term and long-term prognosis.

PMID:41477058 | PMC:PMC12752737 | DOI:10.1515/mr-2025-0039

Metabol Open. 2025 Sep 11;28:100395. doi: 10.1016/j.metop.2025.100395. eCollection 2025 Dec.

ABSTRACT

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are widely used in various manufacturing processes due to their exceptional chemical stability and hydrophobic properties. However, these substances tend to bioaccumulate in the environment and human tissues, posing significant health risks, including endocrine disruption, immune system impairment, and an increased risk of diabetes. Vitamin E, a powerful antioxidant, may potentially attenuate the adverse effects of PFAS on glucose metabolism. Therefore, we utilized data from the 2017-2018 National Health and Nutrition Examination Survey (NHANES), which includes measurements of vitamin E content in a subset of participants, to explore the relationship between PFAS exposures, vitamin E levels, and diabetes risk. Our analysis revealed significant variations in PFAS concentrations across different demographic groups, with males and older individuals exhibiting higher PFAS levels. Elevated PFAS concentrations were associated with an increased risk of diabetes, while vitamin E (specifically alpha-tocopherol) exhibited significant interaction effects with PFAS, modulating blood glucose levels. These findings provide compelling evidence linking PFAS exposures to diabetes risk and highlight the potential moderating role of vitamin E in mitigating PFAS-induced metabolic disturbances. Future research should focus on elucidating the underlying biological mechanisms through which PFAS exert their adverse effects and vitamin E exerts its protective actions, as well as conducting longitudinal studies to establish causality and further explore the complex interplay between PFAS exposures, antioxidant status, and metabolic health.

PMID:41476453 | PMC:PMC12750083 | DOI:10.1016/j.metop.2025.100395

Environ Res. 2025 Dec 31;292:123664. doi: 10.1016/j.envres.2025.123664. Online ahead of print.

ABSTRACT

Aquatic ecosystems face increasing threats from selenium (Se) contamination arising from mining activities. Selenium acts as a potent reproductive toxicant in fish at elevated exposure levels; however, the molecular and physiological underpinnings of its reproductive toxicity remain poorly understood. The current study investigated the reproductive impacts of trophic Se exposure in zebrafish (Danio rerio). The Se-exposed benthic oligochaete (Lumbriculus variegatus), with Se body burdens of 0.65 (control), 17 (low), and 43 (high) μg/g dry weight, was fed to adult zebrafish for 60 days to assess the endocrine and reproductive effects of Se. Trophic Se exposure induced significant increases in the gonadosomatic index (GSI) in females and hepatosomatic index (HSI) in both sexes. Moreover, Se exposure resulted in reduced fecundity, smaller egg diameters, and diminished sperm motility and velocity. The hypothalamic-pituitary-gonadal (HPG) axis was disrupted by Se exposure, with downregulation of gnrh, fshβ, fshr, cyp19b, vtg, and erα genes in females, and altered expression of vtgr, cyp11a, and 3βhsd genes in males. Circulating estradiol (E2) levels decreased in females and males (only with high Se treatment), while 11-ketotestosterone (11 KT) declined in males compared to the respective controls. Plasma vitellogenin (Vtg) also decreased in females but increased in males following dietary Se exposure. Histopathological analysis showed that Se induced ovarian adhesion and oocyte degeneration in females, and degeneration of Sertoli and Leydig cells in males. Collectively, these findings demonstrate that chronic environmentally relevant dietary exposure to Se decreases reproductive fitness of zebrafish by HPG axis dysregulation, underscoring ecological risks from Se contamination.

PMID:41478430 | DOI:10.1016/j.envres.2025.123664

Subcell Biochem. 2026;114:61-121. doi: 10.1007/978-3-032-08530-6_2.

ABSTRACT

The human gut microbiome and noncoding RNAs (ncRNAs) represent interconnected regulatory networks that profoundly influence cancer development, particularly in gastrointestinal and endocrine-related malignancies. This chapter delineates the intricate interplay of microbiome-ncRNA crosstalk in the context of gastrointestinal and endocrine-related cancers.The chapter begins with a comprehensive overview of the taxonomic and functional landscape of the healthy adult gut microbiome. The gut microbiome, comprising trillions of microorganisms, plays a crucial role in endocrine regulation through hormone metabolism, synthesis of bioactive compounds, and modulation of immune responses, thereby establishing a critical crosstalk with the host endocrine system. Dysbiosis, or microbial imbalance, has been linked to endocrine dysfunction and the pathogenesis of various diseases, including gastrointestinal and endocrine-related cancers.We then elucidate the classifications of noncoding RNAs and their function as key molecular regulators in cellular communication, gene expression, and disease progression. NcRNAs contribute significantly to the development and progression of endocrine-related malignancies. The intricate crosstalk between the gut microbiome and host ncRNAs demonstrates how gut dysbiosis can disrupt host ncRNA expression patterns, thereby affecting oncogenic pathways, immune surveillance, and metabolic reprogramming linked to tumor initiation, progression, and metastasis. Conversely, host-derived ncRNAs, secreted into the gut lumen, can directly shape microbial gene expression. In this section, we explore how dysregulation of this axis contributes to carcinogenesis through the promotion of chronic inflammation, epithelial barrier dysfunction, and oncogenic signaling. Therapeutic strategies targeting this interplay, including probiotics, prebiotics, fecal microbiota transplantation, and dietary interventions, are introduced in the context of restoring microbial balance.This comprehensive chapter provides crucial insights into the molecular mechanisms governing microbiome-ncRNA interactions and their implications for cancer biology, offering new perspectives for therapeutic interventions in gastrointestinal and endocrine-related malignancies.

PMID:41479037 | DOI:10.1007/978-3-032-08530-6_2