Curr Neuropharmacol. 2025 Aug 21. doi: 10.2174/011570159X392154250730072830. Online ahead of print.
ABSTRACT
Post-traumatic stress disorder (PTSD) is a chronic and multifactorial psychiatric condition that is often underdiagnosed, particularly when associated with chronic diseases (CDs). These conditions arise from complex interactions among psychosocial, socioeconomic, epigenetic, immune, metabolic, and neurobiological factors. Current treatment options for PTSD and CDs, whether isolated or comorbid, remain suboptimal. Addressing the bidirectional relationship between PTSD and CDs is a pressing global public health challenge, necessitating a deeper understanding of the underlying molecular mechanisms. This review examines the interplay of stress-response and neurochemical factors in PTSD and CDs, highlighting how maladaptive stress responses to trauma can disrupt neurochemical pathways, contributing to the development of CDs, and vice versa. Despite this, a significant gap exists in the number of in vivo model studies that adequately mimic the comorbid symptoms of PTSD and CDs, hindering progress in elucidating shared cellular and molecular pathways. This limitation restricts therapeutic advancements. Therefore, a comprehensive understanding of the neurobiological dysfunctions in the brain and their crosstalk with the immune, cardiovascular, and endocrine systems is critical. Such insights will pave the way for individualized treatment strategies tailored to the unique profiles of patients with PTSD associated with CDs.
PMID:40849771 | DOI:10.2174/011570159X392154250730072830
Ecotoxicol Environ Saf. 2025 Aug 23;303:118884. doi: 10.1016/j.ecoenv.2025.118884. Online ahead of print.
ABSTRACT
Nonylphenol (NP) has been categorized as a persistent organic pollutant and is ranked among the top-priority contaminants by the United Nations Environment Programme. This widely distributed, persistent endocrine-disrupting chemical poses significant risks to ecosystems and human health. While extensive research has explored its occurrence and remediation in wastewater, comparatively fewer studies have examined its fate and behavior in soil and sediments. This review aims to provide a systematic summary of the research progress, environmental behavior, and remediation techniques of NP in soil and sediment. Various remediation approaches have been developed, including physicochemical, microbial, and phytoremediation methods, with chemical and microbial approaches receiving the most attention. Recent advances in chemical remediation have led to the development of innovative technologies such as biochar-based advanced oxidation processes. However, significant challenges and knowledge gaps persist in this area. To address these limitations, future research should focus on the isomer-specific degradation mechanisms, the isolation of anaerobic, high-efficiency NP-degrading microorganisms, and the development of integrated, cross-disciplinary remediation technologies to improve removal efficiency. Effective implementation of these strategies will be essential in mitigating the environmental and health risks associated with NP contamination.
PMID:40850117 | DOI:10.1016/j.ecoenv.2025.118884
Int J Biol Macromol. 2025 Aug 22:147084. doi: 10.1016/j.ijbiomac.2025.147084. Online ahead of print.
ABSTRACT
Phthalates represent the emergent and pervasive environmental pollutants derived from phthalic acids and their constituents, primarily used as plasticizers in polyvinyl chloride products such as packaging materials and toys. Their extensive use and leaching potential raise concerns about exposure and human health. Phthalates are recognized as endocrine-disrupting agents that significantly modify the hepatic enzymes' activities. This study has envisaged assessing the toxicological impact of dicyclohexyl phthalate (DCHP) and diisononyl phthalate (DiNP) on the kinetics of lactate dehydrogenase (LDH) catalyzed reversible reaction in rat liver. The forward and reverse reactions catalyzed by the enzyme, demonstrating the optimal activity at pH 7.4, temperature 37 °C, and pH 6.6, temperature 47 °C, respectively. The enzyme showed a low Km for substrate of the forward reaction while exhibiting a high Km for the substrates of the reverse reaction in the absence of phthalates (DCHP and DiNP). However, the phthalates induced mixed enzyme inhibition and altered the toxicokinetic parameters. Additionally, the IC50, t1/2, and Ki values indicated that DCHP impaired the function of LDH more effectively in both the forward and reverse reactions. The in-silico analysis revealed that DCHP and DiNP induced conformational changes in the mobile loop, active site, and substrate-binding site (Arg169, Arg171), leading to steric hindrance within LDH. The binding affinity and Ki confirmed that DCHP more strongly inhibits the forward reaction of LDH than DiNP. These findings suggested that phthalates induced the structural rearrangements that compromise the catalytic function of LDH and significantly disrupt glycolytic metabolism and energy production by modulating LDH activity.
PMID:40850406 | DOI:10.1016/j.ijbiomac.2025.147084
Reprod Toxicol. 2025 Aug 22:109036. doi: 10.1016/j.reprotox.2025.109036. Online ahead of print.
ABSTRACT
This study reveals how Di-butyl phthalate (DBP), an estrogen-mimicking environmental pollutant, induces hypospadias by inhibiting ferroptosis through ESR1 activation and PINK1-Parkin-dependent mitophagy. Utilizing a prenatal DBP-exposed fetal rat hypospadias model, we observed significant downregulation of pro-ferroptotic ACSL4 and upregulation of anti-ferroptotic GPX4/SLC7A11 in urethral tissues, alongside elevated oxidative stress markers (MDA, Fe²⁺) and reduced glutathione (GSH). In vitro experiments using rat urethral plate fibroblasts (RUPFs) demonstrated that DBP enhanced ferroptosis resistance and promoted proliferation at concentrations below 200μM. Mechanistically, DBP activated ESR1, which triggered mitophagy via the PINK1-Parkin pathway, reducing mitochondrial damage and reactive oxygen species (ROS) accumulation, thereby suppressing ferroptosis. Inhibition or silencing of ESR1 reversed these effects, restoring ferroptosis sensitivity and oxidative stress. These findings unveil a novel ESR1-mitophagy-ferroptosis regulatory axis, linking DBP exposure to hypospadias pathogenesis. The study not only elucidates a previously unrecognized molecular pathway underlying phthalate-induced congenital malformations but also identifies ESR1 and mitophagy as potential therapeutic targets. By integrating in vivo and in vitro approaches, this work advances the understanding of environmental endocrine disruptors' role in developmental toxicity and provides actionable insights for mitigating their health impacts, aligning with current priorities in reproductive and environmental health research.
PMID:40850516 | DOI:10.1016/j.reprotox.2025.109036
Environ Res. 2025 Aug 21:122643. doi: 10.1016/j.envres.2025.122643. Online ahead of print.
ABSTRACT
Bisphenols and parabens are endocrine-disrupting chemicals widely used in food packaging and personal care products. Early-life exposure to these compounds has been associated with adverse health effects, but their potential role in modulating the gut microbiota during childhood remains poorly understood. The objective of this study was to investigate the association between chronic exposure to bisphenols and parabens and gut microbiota diversity, composition, and function in children. A cross-sectional study in 97 Spanish children aged 4-12 year was conducted. Bisphenols and parabens in hair were quantified using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Gut microbiota composition was assessed via 16S rRNA gene sequencing, and functional potential was inferred using PICRUSt2. Associations were explored using linear regression and random forest models, adjusting for age and sex. Total bisphenols and parabens were detected in 100% of the children, with median concentrations of 311.33 ng/g and 1904.11 ng/g, respectively. No significant differences in overall gut microbiota diversity were observed between children with low and high exposure levels to bisphenols and parabens. However, regression models revealed associations between specific microbial genera and individual compounds. Additionally, bisphenol S was negatively associated with a predicted microbial pathway involved in methionine metabolism. Notably, Lachnospiraceae_UCG-001 emerged as a predictive genus for propylparaben exposure. Although gut microbiota composition was similar across exposure levels, specific taxa and functional pathways were linked to chronic bisphenol and paraben exposure. These findings support the need for further research on the health implications of early-life exposure to these endocrine-disrupting chemicals.
PMID:40849015 | DOI:10.1016/j.envres.2025.122643
Reprod Biol Endocrinol. 2025 Aug 22;23(1):118. doi: 10.1186/s12958-025-01442-8.
ABSTRACT
Emerging evidence highlights the decline of testosterone levels among young males, linked to modern lifestyle shifts rather than aging alone. This exploratory cross-sectional study investigates the interplay between modifiable lifestyle factors and testosterone levels in 50 males aged 18-22 years, focusing on underrepresented variables such as exercise type, carbonated beverage intake, and sunlight exposure. Serum testosterone levels were measured via chemiluminescent immunoassay, and lifestyle data were collected through previously validated questionnaires. Multiple regression analyses revealed hypertrophy training (β = 20.3, p < 0.001), sunlight exposure > 60 min (β = 10.3, p = 0.03), and supplement use (β = 20.5, p < 0.001) as positive predictors of testosterone. Conversely, daily carbonated beverage consumption (β=-10.2, p = 0.01), tobacco use (β=-15.6, p < 0.001), and sleep deprivation (β=-18.2, p < 0.001) were significant negative correlates. Diet type influenced outcomes, with non-vegetarians showing higher testosterone (β = 8.7, p = 0.03) compared to vegetarians. Notably, BMI and chronic diseases were nonsignificant in this young cohort. These findings underscore the multifactorial nature of testosterone regulation, emphasizing holistic lifestyle interventions-such as resistance training, reduced ultra-processed food intake, and sleep optimization-as critical for endocrine health in urbanized youth. The study challenges traditional obesity-centric frameworks, advocating for holistic approaches to mitigate endocrine disruption in emerging adulthood.
PMID:40847396 | DOI:10.1186/s12958-025-01442-8
Sci Rep. 2025 Aug 23;15(1):31075. doi: 10.1038/s41598-025-17257-x.
ABSTRACT
Phthalate esters (PAEs), a group of well-known endocrine-disrupting chemicals (EDCs), are extensively used in plastic manufacturing and are recognized for their contribution to environmental pollution and potential adverse health effects. Rivers in urban and recreational areas are increasingly threatened by plastic-derived pollutants, yet there is a lack of data on the occurrence, distribution, and risks of PAEs in such environments in Iran. The Torghabeh River, a popular recreational site near Mashhad, may be particularly vulnerable to phthalate pollution due to tourism, waste discharge, and urban runoff. Therefore, this study aimed to identify and quantify PAEs in the water and sediment of the Torghabeh River and to assess their associated human and ecological risks. Water and sediment samples were collected from various locations along the river. After extraction using solid-phase extraction (SPE) for water samples and ultrasonic extraction for sediment samples, PAEs were identified using gas chromatography-mass spectrometry (GC-MS). The results showed that the mean concentration of Σ6PAEs in water was 11,030.8 ng/L, ranging from non-detectable (ND) to 17,477.07 ng/L. In surface sediments, the mean concentration of Σ7PAEs was 9,714.98 ng/g (range: ND-29,226.06 ng/g), while deeper sediments had a mean concentration of 7858.46 ng/g (range ND-15,084.94 ng/g). Di (2-ethylhexyl) phthalate (DEHP) was the predominant compound detected in both water and sediment samples. PAE concentrations were generally higher in sediments than in water. The hazard quotient (HQ) and hazard index (HI) values for human exposure were below established threshold levels; however, DEHP posed a higher dermal exposure risk for children. Ecological risk assessment revealed that Diisobutyl phthalate (DiBP) had a risk quotient (RQ) greater than 1 for fish in both water and sediment, while DEHP exceeded an RQ of 1 for all aquatic species in water. In conclusion, phthalate esters were present at notable concentrations in both water and sediment of the Torghabeh River, with higher accumulation observed in sediments. Although human health risks were generally low, certain compounds-particularly DEHP and DiBP-posed significant ecological risks and increased dermal exposure concerns for children.
PMID:40849536 | DOI:10.1038/s41598-025-17257-x
Cureus. 2025 Jul 21;17(7):e88458. doi: 10.7759/cureus.88458. eCollection 2025 Jul.
ABSTRACT
The COVID-19 pandemic has significantly impacted global health systems, with emerging evidence suggesting unique implications for pediatric populations with endocrine disorders. While children generally experience milder acute COVID-19 symptoms, those with pre-existing endocrine conditions may face heightened risks due to the interplay between viral infection and endocrine homeostasis. This systematic review aimed to synthesize evidence on the relationship between endocrine disorders and COVID-19 severity in children, focusing on disease outcomes, metabolic control, and management challenges during the pandemic. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, a systematic search was conducted across PubMed, Scopus, Web of Science, and Cochrane Library. Ten studies meeting the inclusion criteria were selected after screening 638 records. Data were extracted on study characteristics, patient demographics, endocrine disorders, COVID-19 severity outcomes, and key findings. Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) tool. A narrative synthesis was performed due to heterogeneity in study designs and outcomes. The review revealed significant pandemic-related disruptions in pediatric endocrine health, including increased central precocious puberty cases and elevated BMI z-scores in children with obesity. Diabetes outcomes were mixed: type 1 diabetes patients had better mortality prognoses than type 2 diabetes patients, but diabetic ketoacidosis rates surged. Thyroid dysfunction and stable medication adherence in congenital adrenal hyperplasia were also noted. Risk of bias varied, with three studies rated low, five rated moderate, and two rated as high risk of bias. COVID-19 exacerbated endocrine disorders in children through direct viral effects and indirect lifestyle and healthcare disruptions. The findings underscore the need for adaptive care strategies, including telehealth and mental health support, to mitigate long-term impacts. Future research should prioritize prospective studies to evaluate sustained effects and interventions for at-risk populations.
PMID:40842802 | PMC:PMC12367286 | DOI:10.7759/cureus.88458
Sci Total Environ. 2025 Aug 21;998:180251. doi: 10.1016/j.scitotenv.2025.180251. Online ahead of print.
ABSTRACT
Kidney transplanted children are exposed to phthalates and phenols, potentially harmful environmental endocrine-disrupting chemicals. Urinary levels of phthalates and phenols in 52 Norwegian kidney transplanted children were compared with levels in healthy children, in children with chronic kidney disease, evaluated against selected variables, and where estimated daily intakes (EDIs) were back-calculated and assessed as part of a risk assessment. Urine samples were collected at a mean age of 11.6 (range 2.3-18) years, after a median of five (range 1.0-15.5) years after the transplant. Kidney transplanted Norwegian children's urinary levels of phthalates and phenols showed a broad range between minimum and maximum levels, with lower levels measured in older children and as time passed after the transplant. Most levels of phthalate metabolites were lower, however 2-5 times higher for the sum of (∑) di-iso-nonyl phthalate (DiNP) metabolites, methylparaben, propylparaben (PrPa), and triclosan, compared to other Norwegian children with presumed normal kidney function. Girls had higher concentrations of monoethyl phthalate, with no differences observed among children with or without overweight or hypertension. The risk assessment showed that at least 10 % of children were at risk of adverse health effects due to PrPa exposure, as well as a few children at maximum exposure to metabolites of ∑DiNP, and to ∑ di-n-butyl phthalate, butyl benzyl phthalate, di(2-ethylhexyl) phthalate and DiNP. All included kidney transplanted children had EDI above the threshold value for bisphenol A, suggesting that this widely used chemical may pose a health risk to this patient group. Clinical trial registration no.: NCT01008306.
PMID:40845701 | DOI:10.1016/j.scitotenv.2025.180251
Toxicol Appl Pharmacol. 2025 Aug 20;504:117523. doi: 10.1016/j.taap.2025.117523. Online ahead of print.
ABSTRACT
A broad range of anthropogenic chemicals have been reported to display estrogenic (ER) or antiandrogenic bioactivity using high throughput screening (HTS) in vitro assays. Some regulatory agencies have developed tiered in vitro - in vivo endocrine screening batteries in which positive in vitro results automatically "trigger" studies with laboratory animals. Since in vitro assays can produce a number of false positive and false negative results, automatically triggering in vivo testing could result in the unnecessary use of animals and other resources. The in vitro false positive rate may be particularly high with reported AR antagonists, because many nonspecific mechanisms can disrupt competitive AR dose-response assays such that chemicals falsely appear to be competitive AR ligands. In the current investigation, we illustrated the utility of in vitro Schild regression to interrogate the in vitro ER and/or anti-AR bioactivity of pesticides which were positive in HTS ER or AR models. Schild regression discriminates chemicals that act as true competitive receptor ligands from those that disrupt signaling via noncompetitive mechanisms. The chemicals studied included seven pesticides listed by EPA as high priority for in vivo ER or anti-AR testing and two pesticides listed as low priority, as well as 17β-estradiol (E2) and hydroxyflutamide (OHF) as ER and anti-AR reference ligands. Two out of four pesticides tested for ER agonist activity were cytotoxic, and four out of seven pesticides tested for AR antagonist activity, plus OHF, were true competitive AR antagonists (two true positives and two false negatives). Herein, we propose a tiered strategy that includes a more in-depth analysis of in vitro bioactivity using Schild regression to determine if HTS or other in vitro bioactivity data results from true competitive receptor antagonism or some nonspecific mechanism. This strategy could reduce unnecessary in vivo testing for chemicals that are not AR antagonists in vitro.
PMID:40846137 | DOI:10.1016/j.taap.2025.117523
Cell Death Discov. 2025 Aug 22;11(1):396. doi: 10.1038/s41420-025-02697-1.
ABSTRACT
The liver-adipose axis represents a crucial regulatory network that governs systemic lipid homeostasis, with signals originating from the liver orchestrating the plasticity of adipose tissue through diverse mechanisms. A comprehensive understanding of these bidirectional communication pathways may uncover novel therapeutic approaches for metabolic disorders. Our research demonstrates that exposure to cold stimulates the liver to secrete exosomes, which enhance thermogenic activation in adipose tissue, as observed in both in vitro and in vivo models. This enhancement of thermogenesis is mechanistically associated with the cold-induced upregulation of hepatocyte-derived exosomal miR-293-5p. Importantly, the pharmacological administration of a miR-293-5p agomir significantly mitigates diet-induced obesity and related metabolic dysfunctions in murine models. Through mechanistic analysis, we identified Tet1 as a direct downstream target of miR-293-5p, noting that the ectopic expression of Tet1 disrupts the thermogenic programming of brown adipose tissue (BAT) independently of miR-293-5p modulation. Our findings establish cold-activated hepatocyte exosomes as endocrine signaling mediators that carry thermogenic microRNA cargos, with miR-293-5p emerging as a key regulator.
PMID:40846699 | DOI:10.1038/s41420-025-02697-1
Environ Res. 2025 Aug 19:122623. doi: 10.1016/j.envres.2025.122623. Online ahead of print.
ABSTRACT
INTRODUCTION: Environmental pollution poses increasing threats to public health, particularly in metabolic disorders. Steatotic liver disease (SLD) is characterized by metabolic dysfunctions of the liver and affects over one-third of the global population. However, whether exposure to environmental pollutants would increase the risk of SLD remains poorly understood.
AIM: To evaluate the association between exposure to environmental pollutants and the SLD risk.
METHODS: A systematic search of Medline, Embase, and Web of Science databases, along with manually reviewed reference lists, was conducted from inception until May 30, 2025. Observational studies reporting quantitative effect estimates of environmental pollutants and SLD risk in adults were included, following PRISMA and MOOSE guidelines. Random-effect models were applied to pool the data.
RESULTS: A total of 34 studies were included. Environmental pollutants in this study were categorized as air pollutants, endocrine-disrupting chemicals (EDCs), and heavy metals. Significant associations with increased SLD risk were observed for particulate matter (PM2.5: OR = 1.23; PM10: OR = 1.07; PM1: OR = 1.45) and nitrogen dioxide (NO2: OR = 1.19) per 10 μg/m3 increase. Among EDCs, exposure to bisphenol A (BPA: OR = 1.42), MECPP (OR = 1.43), MEHHP (OR = 1.54), MEOHP (OR = 1.38), and PFOA (OR = 1.23) was correlated with elevated SLD risk. Exposure to heavy metals, including lead (Pb: OR = 1.61), cadmium (Cd: OR = 2.32), mercury (Hg: OR = 2.41), barium (Ba: OR = 1.16), arsenic (As: OR = 1.09), and cobalt (Co: OR = 1.18) was significantly associated with increased SLD risk.
CONCLUSIONS: Exposure to a wide range of environmental pollutants significantly increased SLD risk, underscoring the need for public health interventions to mitigate pollutant exposure and its contribution to SLD development.
PMID:40840603 | DOI:10.1016/j.envres.2025.122623
J Hazard Mater. 2025 Aug 16;497:139582. doi: 10.1016/j.jhazmat.2025.139582. Online ahead of print.
ABSTRACT
Bisphenol A (BPA) is a frequently used endocrine-disrupting chemical widely distributed in the environment, necessitating effective removal strategies. This study aimed to isolate and characterize a highly efficient BPA-degrading bacterial strain, Sphingobium yanoikuyae GDP, and to elucidate the enzymatic degradation pathways of BPA mediated by the P450 enzyme BisdB, including the identification of novel metabolites using 13C stable isotope-assisted untargeted liquid chromatography-tandem mass spectrometry. In this study, a BPA-degrading microbial community, D45, was isolated from contaminated soil and degraded 400 mg L-1 of BPA within 24 h. Ten metabolites were identified during BPA degradation by D45, including 4,4'-dihydroxybenzophenone (4-DHBP), a novel metabolite. Sphingobium yanoikuyae strain GDP was subsequently obtained, which degraded BPA via the same routes as D45 but exhibited enhanced BPA-degrading efficiency. Genomic and gene expression analyses revealed that a P450 enzyme BisdB was essential for BPA degradation. BisdB produced at least eight metabolites, including 4-DHBP, through stepwise BPA catalysis, two of which were challenging to transform further. This study revealed the precise role of bacterial P450 in BPA degradation and illustrated the complete BPA degradation pathways. These findings provide potential opportunities for synthetic biology-based applications of the GDP strain and BisdB to degrade BPA.
PMID:40840048 | DOI:10.1016/j.jhazmat.2025.139582
Rev Invest Clin. 2025 May-Jun;77(3):100008. doi: 10.1016/j.ric.2025.100008. Epub 2025 Jul 1.
ABSTRACT
Polycystic ovary syndrome (PCOS) is a multifactorial endocrine and metabolic disorder in women of reproductive age characterized by hormonal imbalances, menstrual irregularities, and changes in ovarian morphology. Excess body fat plays a significant role in the clinical development of PCOS. The complex relationship between adiposity and PCOS involves disruptions in hormonal balance and inflammatory processes, which both contribute to the clinical and phenotypic manifestations of the syndrome. Insulin resistance is a significant factor linking adiposity and PCOS. Moreover, reduced fertility is associated with adiposity in PCOS, with obesity exacerbating anovulation. Recent studies have raised questions about the role of androgen exposure during fetal life, including genetic factors related to PCOS identified in genome-wide association studies and Mendelian randomization studies. Managing PCOS should concentrate on addressing adiposity as a crucial target, positively impacting the syndrome, particularly regarding reproductive and fertility outcomes. This review aims to understand how metabolic conditions such as obesity and insulin resistance are linked to PCOS and how early prenatal androgen exposure is involved in its etiology. Particular attention is given to its role in developmental programming, fat distribution, and fat type, as well as how these factors contribute to the onset of metabolic disturbances in adulthood.
PMID:40838815 | DOI:10.1016/j.ric.2025.100008
Talanta. 2025 Aug 18;297(Pt B):128722. doi: 10.1016/j.talanta.2025.128722. Online ahead of print.
ABSTRACT
Polychlorinated biphenyls (PCBs) are known to pose serious risks to human health, including carcinogenicity, neurotoxicity and endocrine disruption. Due to these hazards to human health, development of sensitive and reliable methods for analysis of PCBs attracts considerable attention. Herein, a hierarchical flower-like Co3O4/Al2O3 composite was employed as new coating material of headspace solid-phase microextraction (HS-SPME) for the first time. The Co3O4/Al2O3 composite was synthesized via thermal annealing of a cobalt-aluminum layered double hydroxide (CoAl-LDH) precursor in air. Among synthesized materials, the Co3O4/Al2O3-2 composite demonstrated exceptional thermal stability, high specific surface area, and well-defined porous structure. These properties facilitate superior enrichment performance of trace PCBs. When coupled with gas chromatography-flame ionization detection (GC-FID), the Co3O4/Al2O3-2-coated fiber achieved detection limits of 0.0003-0.001 ng mL-1 and enrichment factors of 10238-11768, which was a significant improvement over existing methods. The method exhibited a wide linear range (0.001-30 ng mL-1), spiked recoveries of 86.70-113.69 %, and relative standard deviations not exceeding 11.39 %, demonstrating exceptional adsorption performance. This work introduces an effective SPME coating while expanding the environmental monitoring applications of Co3O4/Al2O3 composites.
PMID:40839964 | DOI:10.1016/j.talanta.2025.128722
Org Biomol Chem. 2025 Aug 20. doi: 10.1039/d5ob01091h. Online ahead of print.
ABSTRACT
17β-estradiol (E2), a potent endocrine-disrupting chemical, is frequently detected in aquatic environments and food samples, where it poses serious ecological and public health risks even at trace levels. Herein, we report a label-free ratiometric fluorescent aptasensor for the sensitive and selective detection of E2, employing ethyl violet (EV) as a near-infrared (NIR) responsive dye and fluorescein (FL) as an internal reference. EV was identified through systematic screening based on its strong fluorescence response upon aptamer binding. The resulting sensor exhibited a pronounced ratiometric response, a low detection limit of 0.25 μM, and excellent selectivity against structural analogues. Its practical performance was validated using farm wastewater samples, yielding recoveries of 94.92-110.49% and relative standard deviations below 6.15%. With an estimated cost of approximately $0.11, this aptasensor provides a simple, economical, and reliable tool for monitoring estrogenic pollutants in complex environmental water samples.
PMID:40832813 | DOI:10.1039/d5ob01091h
Naunyn Schmiedebergs Arch Pharmacol. 2025 Aug 20. doi: 10.1007/s00210-025-04487-z. Online ahead of print.
ABSTRACT
Breast cancer remains a leading cause of cancer-related morbidity in women worldwide, with hormone receptor-positive (HR +) subtypes comprising approximately 70% of cases. Despite advances in endocrine therapies, the development of hormone resistance poses a major challenge, often leading to treatment failure and disease progression. This review addresses the central problem of resistance in HR + breast cancer (HR + BC), focusing on key mechanisms such as mutations in the estrogen receptor (ER), activation of alternative survival pathways including the PI3K/Akt/mTOR axis, and the inherent heterogeneity of tumors. Emerging therapies aim to overcome these barriers by combining hormone treatments with targeted inhibitors. Special emphasis is placed on novel approaches involving mitochondrial disruption, epigenetic modulation, and manipulation of the tumor microenvironment. These strategies reflect a shift toward personalized medicine, where molecular profiling and biomarker identification guide individualized treatment plans. Understanding and targeting the multifactorial nature of resistance in HR + BC is essential to improving therapeutic outcomes. A multidisciplinary, mechanism-based approach offers the most promise for restoring treatment sensitivity and enhancing long-term survival.
PMID:40833601 | DOI:10.1007/s00210-025-04487-z
Ecotoxicol Environ Saf. 2025 Aug 19;303:118827. doi: 10.1016/j.ecoenv.2025.118827. Online ahead of print.
ABSTRACT
Placental microplastic exposure has emerged as a potential environmental risk factor affecting fetal development. This study investigates the association between placental microplastic burden and umbilical cord hormone levels in a cohort of pregnant women from Shenyang, China. A total of 1324 pregnant women during 2022-2023 were enrolled. Placental microplastics were quantified using a laser direct infrared (LD-IR) chemical imaging system, targeting polyvinyl chloride (PVC), polypropylene (PP), and polybutylene succinate (PBS). Umbilical cord blood cortisol, cortisone, dehydroepiandrosterone (DHEA), and androstenedione were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Regression models were applied to assess individual microplastic associations, while quantile-based g-computation (g-comp) and Bayesian Kernel Machine Regression (BKMR) were used to evaluate mixture effects. Microplastics were detected in all placental samples, with a median total concentration of 12 particles/10 g. Placental microplastic exposure was significantly associated with altered fetal hormone levels. Higher PVC, PBS, and total microplastic concentrations were linked to lower cortisol levels, while PVC, PP, and total microplastics were associated with reduced cortisone. In contrast, PBS and total microplastics were positively associated with DHEA, and PVC, PBS, and total microplastics correlated with increased androstenedione. The cortisol/DHEA and glucocorticoid/androgenic ratios were significantly reduced with higher microplastic exposure, suggesting endocrine disruption. Mixture analysis confirmed these trends, showing decreased glucocorticoids and increased androgens, with sex-stratified analysis indicating stronger cortisol reductions in boys and higher DHEA in girls. Overall, placental microplastic exposure was associated with altered fetal hormone levels, suggesting potential endocrine disruption while further studies are needed.
PMID:40834760 | DOI:10.1016/j.ecoenv.2025.118827
Sci Total Environ. 2025 Aug 19;998:180262. doi: 10.1016/j.scitotenv.2025.180262. Online ahead of print.
ABSTRACT
Phthalate esters (PAEs), which are widely used as plasticizers in various industrial processes, pose significant risks to ecosystems and human health as emerging pollutants. This study aimed to compare different methods for extracting PAEs, quantifying their concentrations, and assessing the health risks associated with exposure to these contaminants. Based on the reviewed studies, solid-phase extraction (SPE) was the preferred sample preparation technique in approximately 60 % of cases due to its efficiency, low solvent consumption, and strong enrichment capabilities. Moreover, gas chromatography-mass spectrometry (GC-MS) was the most commonly used detection method, applied in 78.8 % of the studies for accurate quantification. The reported concentrations of PAEs in river water ranged from 100 to 300,000 ng/L. Studies indicated that di(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP) were the most frequently detected PAEs, present in 90 % and 91.25 % of river systems, respectively. Peak concentrations were reported as 60 μg/L in water, 41.4 μg/g in sediments, and 1.586 μg/g in aquatic organisms. Studies have indicated that both DEHP and DBP exhibit high Risk Quotient (RQ > 1) values, suggesting significant ecological risks to aquatic organisms. These risks include potential endocrine disruption, growth inhibition, and metabolic dysfunction, as observed in environmental studies. Additionally, some studies have reported high Hazard Quotient (HQ > 1) values for human exposure, indicating possible non-carcinogenic health effects resulting from chronic intake. Effective monitoring and mitigation strategies are essential to minimize the environmental and public health impacts of PAEs. Overall, this review highlights the widespread occurrence and persistence of PAEs in riverine environments, emphasizing their potential to disrupt ecological balance and pose health risks. Continued research, along with stricter regulatory measures, is crucial to control their release and safeguard environmental and human health.
PMID:40834516 | DOI:10.1016/j.scitotenv.2025.180262
J Hazard Mater. 2025 Aug 19;497:139542. doi: 10.1016/j.jhazmat.2025.139542. Online ahead of print.
ABSTRACT
Triphenyltin hydroxide (TPTH) is an organotin fungicide that causes endocrine disruption and reproductive malformation in aquatic organisms. The objectives of this study were to determine the photodegradation kinetics, identify the transformation products, and measure the residual toxicity of TPTH during UV-254 and UV-H2O2 treatment. The quantum yield of TPTH was 0.18 ± 0.02 mol Ein-1 for direct photolysis at 254 nm. The effects of pH (4-10), ionic strength (0.001-0.1 M), and photosensitizers (hydrogen peroxide, dissolved organic matter) on TPTH photodegradation were evaluated to simulate environmental conditions and treatment scenarios. Solution pH and ionic strength had a negligible influence on TPTH degradation kinetics. However, TPTH degradation was enhanced in the UV-H2O2 process due to reaction with hydroxyl radicals. The second-order rate constant for TPTH reaction with hydroxyl radicals was (7.81 ± 0.37)× 108 M-1 s-1. The primary phototransformation products involved hydroxylation of the phenyl groups in TPTH. The toxicity of TPTH and its phototransformation products were measured using a novel bacterial growth inhibition assay with the potency equivalents approach, and the results indicated that both direct photolysis and advanced oxidation generated toxic products. Overall, this study highlighted the need for advanced treatment systems for organotin chemicals and careful consideration of the photoproduct toxicity.
PMID:40834541 | DOI:10.1016/j.jhazmat.2025.139542
Aquat Toxicol. 2025 Aug 12;287:107540. doi: 10.1016/j.aquatox.2025.107540. Online ahead of print.
ABSTRACT
This study aimed to assess the toxicity of bisphenol A (BPA) and bisphenol F (BPF) in rainbow trout following six weeks of dietary exposure. Fish were exposed to BPA, BPF, or their combination at nominal concentrations of 10 and 1000 µg/kg (i.e., BPAlow, BPAhigh, BPFlow, BPFhigh, BPA+BPFlow). Haematological analysis revealed a significant reduction (p < 0.05) in leukocytes and lymphocytes, but only in the BPFhigh group. Plasma biochemical markers showed significant increases (p < 0.05) in creatinine in BPAlow and elevated amylase activity in both BPF groups. Surprisingly, markers of endocrine disruption, such as vitellogenin and thyroxine, were significantly elevated (p < 0.05) only in BPFhigh and BPA+BPFlow, despite no pathological changes being observed in the gonads. Oxidative stress markers were significantly affected, with increased catalase activity (p < 0.05) in the liver, kidney, and gill across all groups. Additionally, plasma DNA damage was significantly (p < 0.05) reduced in BPAlow and BPFhigh. In contrast, significant elevations (p < 0.05) of ceruloplasmin and ferric reducing/antioxidant power were observed in the BPA+BPFlow and both BPF groups, respectively. Histological examination revealed liver congestion and dystrophy in both BPA groups, hyaline droplet degeneration in the tubular epithelial cells of the caudal kidney across all exposed groups, and deformation of gill filaments in BPA+BPFlow and both BPA groups. Our findings underscore that the increasing use of BPA analogues may pose a greater risk than the original compound in certain contexts, emphasizing the need for further studies to understand the long-term effects of bisphenol analogues, particularly at environmentally relevant concentrations and in mixtures.
PMID:40834665 | DOI:10.1016/j.aquatox.2025.107540
Ecotoxicol Environ Saf. 2025 Aug 19;303:118827. doi: 10.1016/j.ecoenv.2025.118827. Online ahead of print.
ABSTRACT
Placental microplastic exposure has emerged as a potential environmental risk factor affecting fetal development. This study investigates the association between placental microplastic burden and umbilical cord hormone levels in a cohort of pregnant women from Shenyang, China. A total of 1324 pregnant women during 2022-2023 were enrolled. Placental microplastics were quantified using a laser direct infrared (LD-IR) chemical imaging system, targeting polyvinyl chloride (PVC), polypropylene (PP), and polybutylene succinate (PBS). Umbilical cord blood cortisol, cortisone, dehydroepiandrosterone (DHEA), and androstenedione were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Regression models were applied to assess individual microplastic associations, while quantile-based g-computation (g-comp) and Bayesian Kernel Machine Regression (BKMR) were used to evaluate mixture effects. Microplastics were detected in all placental samples, with a median total concentration of 12 particles/10 g. Placental microplastic exposure was significantly associated with altered fetal hormone levels. Higher PVC, PBS, and total microplastic concentrations were linked to lower cortisol levels, while PVC, PP, and total microplastics were associated with reduced cortisone. In contrast, PBS and total microplastics were positively associated with DHEA, and PVC, PBS, and total microplastics correlated with increased androstenedione. The cortisol/DHEA and glucocorticoid/androgenic ratios were significantly reduced with higher microplastic exposure, suggesting endocrine disruption. Mixture analysis confirmed these trends, showing decreased glucocorticoids and increased androgens, with sex-stratified analysis indicating stronger cortisol reductions in boys and higher DHEA in girls. Overall, placental microplastic exposure was associated with altered fetal hormone levels, suggesting potential endocrine disruption while further studies are needed.
PMID:40834760 | DOI:10.1016/j.ecoenv.2025.118827
Toxicology. 2025 Aug 18;518:154264. doi: 10.1016/j.tox.2025.154264. Online ahead of print.
ABSTRACT
Polychlorinated biphenyls (PCBs) have been reported to be associated with type 2 diabetes mellitus (T2DM); thus, the knowledge of their endocrine disruption mechanisms would be vital for assessing health risks. This study revealed the potential mechanism of abnormal glucose metabolism due to acute PCB-153 exposure in HepG2 cells through integrated transcriptome and DNA methylation analysis. Based on a joint analysis of two omics, the random forest machine learning model was established with 200 trees and cross-validated five times. Potential biomarkers identified by machine learning pointed to impaired mitochondrial function. Subsequent validation confirmed PCB-153-induced mitochondrial dysfunction, evidenced by reduced mitochondrial DNA copy number (mtDNAcn), adenosine triphosphate (ATP) production, mitochondrial membrane potential, and ATPase activity, alongside altered morphology and elevated reactive oxygen species (ROS). Critically, abnormal glucose metabolism was significantly attenuated and even recovered to control levels after enhancement of mitochondrial function, suggesting that PCB-153 promoted glucose metabolic defects in relation to mitochondrial dysfunction. The decline of mtDNAcn in the T2DM nested case-control population provided further evidence for long-term PCBs exposure inducing mitochondrial dysfunction. In addition, significant multiplicative and additive interactions were observed between mtDNAcn and PCB-138, PCB-153, lowly chlorinated PCBs, highly chlorinated PCBs, ΣNDL-PCBs on the 5-year FBG levels changes (Pinteraction: 0.004-0.03; RERI: -0.44 to -0.31; AP: -0.39 to -0.21). Our findings highlighted the importance of maintaining normal mitochondrial function in glucose metabolism of non-dioxin-like PCBs exposure and provided new insights into T2DM pathogenesis caused by PCBs exposure.
PMID:40834992 | DOI:10.1016/j.tox.2025.154264
Environ Pollut. 2025 Aug 19;384:126984. doi: 10.1016/j.envpol.2025.126984. Online ahead of print.
ABSTRACT
Emerging contaminants (ECs) have drawn significant attention due to their adverse effects on aquatic ecosystems. This study investigated the spatiotemporal distribution and ecological risks of 43 ECs in surface water and examined their fate in wastewater treatment plants (WWTPs) in the lower Yangtze River basin. In surface water, 34 ECs were detected, including 13 antibiotics, 4 endocrine-disrupting compounds, 9 pharmaceutical and personal care products, 4 perfluoroalkyl and polyfluoroalkyl substances and 4 organophosphate esters. Specifically, doxycycline, ethinyl estradiol, salicylic acid, perfluorooctanoic acid and triisobutyl phosphate showed dramatic spatiotemporal variations. Temporally, doxycycline, salicylic acid, ibuprofen, diclofenac and perfluorooctanoic acid peaked in winter, whereas ethinyl estradiol and triisobutyl phosphate showed higher concentrations in summer and autumn. Spatially, bisphenol A and octyl phenol were more concentrated in the downstream section, while triisobutyl phosphate levels were higher in the upstream section. Risk assessment indicated 82 out of 87 water samples posed medium or high ecological risk, and sulfamethoxazole, roxithromycin, ethinyl estradiol and octyl phenol were identified as primary contributors. Although the removal efficiencies of ECs in industrial and municipal WWTPs were 87.1 ± 1.5 % and 83.6 ± 1.5 %, respectively, EC concentrations in effluents were 2.70 and 6.15 times higher than those in surface water. Correlation analysis further confirmed that the discharges from WWTPs were highly related to the existence of these ECs in the lower Yangtze River. The effluent concentrations of perfluorooctanoic acid, doxycycline, Triethyl phosphate, roxithromycin and Tris-(2-chloroisopropyl) phosphate usually exceeded 20 ng/L due to their low removal efficiencies, where moreover, ECs with high influent concentrations but removal efficiencies above 80 % still posed significant effluent risks. These results suggest that, besides adopting advanced treatment technologies (e.g., adsorption, ion exchange), source control is also crucial. This study offers key insights into Yangtze River EC pollution, supporting better monitoring and management.
PMID:40835102 | DOI:10.1016/j.envpol.2025.126984
Nat Commun. 2025 Aug 20;16(1):7753. doi: 10.1038/s41467-025-63235-2.
ABSTRACT
In the field of wastewater treatment, the regulation of free radical and non-radical routes has been one of the major challenges. This study investigates the regulation of radical and non-radical oxidation pathways in the peroxymonosulfate (PMS) oxidation system by controlling the calcination temperature of carbon materials and constructing bimetallic single-atom catalysts (NC-FeMn(TA)). Density functional theory calculations and experimental tests indicate that increasing the pyridinic nitrogen content and incorporating single metal atoms in nitrogen-doped carbon materials result in a predominantly non-radical oxidation process. In contrast, enhancing the content of graphitic and pyrrolic nitrogen species and introducing bimetallic catalytic centers promote a radical oxidation pathway. The NC-FeMn(TA)/PMS system demonstrates high oxidation performance over a broad pH range, exhibiting significant interference resistance and stability, with 100% degradation of target pollutants after 22 cycles and complete removal of emerging pollutants (including pharmaceuticals and personal care products, endocrine disrupting chemicals, dyes and chemical materials) within 5 min. This system's remarkable performance suggests broad application potential in water pollution control field.
PMID:40835831 | PMC:PMC12368032 | DOI:10.1038/s41467-025-63235-2
J Ovarian Res. 2025 Aug 19;18(1):189. doi: 10.1186/s13048-025-01774-4.
ABSTRACT
BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder with significant impacts on women’s reproductive health. Interleukin (IL)-2 receptor subunit gamma (IL2RG), a common receptor for IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21, has been shown to interrupt estrous cycle, yet its role in PCOS remains unclear.
RESULTS: The evaluated expression levels of IL2RG in human granulosa cells (GCs) and IL2RG-dependent cytokines (IL-2, IL-4, IL-15) in follicular fluid were demonstrated in 18 PCOS patients and 22 control subjects. The positive correlation between IL2RG and PCOS was analysed through GEO databases. In vivo, we found that in the PCOS model (6 mg/100 g body-weight of dehydroepiandrosterone subcutaneous injection for 21 days), the ovarian index, testosterone, glucose, and LH/FSH levels were elevated, and the estrous cycle was disrupted. Knocking down IL2RG (KO) restored the above levels. However, in the dehydroepiandrosterone-treated group, these levels did not recover even after IL2RG was knocked-down. The decreased expression of Gasdermin E (GSDME) but increased caspase-3 level in IL2RG KO rats compared with WT were found. In vitro, knockdown of IL2RG by siRNA inhibited caspase-3-mediated GSDME cleavage in testosterone-induced KGN cells. Furthermore, the caspase-3 inhibitor Z-DEVD-FMK and the caspase-1 inhibitor Belnacasan alleviated pyroptosis in testosterone-induced KGN cells by lactate dehydrogenase test, fluorescence assay, and flow cytometry.
CONCLUSIONS: IL2RG is expressed higher in PCOS patients, exerting an inhibitory effect on caspase-3-mediated GSDME cleavage upon knockdown. However, the knockout of IL2RG led to the conversion of GSDME-mediated pyroptosis into apoptosis. This study explores the function of IL2RG and provides insights for therapeutic targets in PCOS.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13048-025-01774-4.
PMID:40830889 | PMC:PMC12362916 | DOI:10.1186/s13048-025-01774-4
Toxicol Res (Camb). 2025 Aug 18;14(4):tfaf120. doi: 10.1093/toxres/tfaf120. eCollection 2025 Aug.
ABSTRACT
Bisphenol A (BPA), widely used in plastics and resins, has raised health concerns for its endocrine-disrupting effects. BPA analogues such as bisphenol S (BPS) and bisphenol F (BPF) emerged as alternatives but exhibit similar risks. Despite regulations on BPA in many countries, alternatives remain insufficiently controlled. Although the safety of BPS and BPF has not been sufficiently verified, these compounds have already been detected in various environmental sources and human urine, raising serious concerns. While bisphenols are expected to have various adverse effects, research remains limited. This study investigates the adverse effects of bisphenols mixture on rats from fetal stage to young adulthood by analyzing transcriptomes in multiple tissues-liver, kidney, thyroid gland, and reproductive organs-and by gender, to identify key genes affected by bisphenol exposure. Dams were orally administered test substances from gestational day 6 to lactation day 6, and F1 pups received the same substances at half the concentration from postnatal day 7 to day 63. Transcriptome analysis of the collected tissues identified core genes related to high-density lipoprotein metabolism and hormone secretion, providing insights into mechanisms through which BPA may disrupt hormonal balance. Furthermore, the study suggests that combined exposure to BPA, BPS, and BPF produces distinct effects compared to BPA alone, with pronounced impacts on the thyroid and reproductive organs, despite individual concentrations being below the no-observed-adverse-effect-level. These findings highlight the potential cumulative impact of endocrine disrupting chemicals in the body.
PMID:40831461 | PMC:PMC12360700 | DOI:10.1093/toxres/tfaf120
medRxiv [Preprint]. 2025 Aug 12:2025.08.11.25333027. doi: 10.1101/2025.08.11.25333027.
ABSTRACT
Polycystic ovary syndrome is the most common endocrine condition in women and anovulatory cause of female infertility. While a pro-inflammatory cytokines and leukocyte bias in systemic circulation is well-documented in PCOS, it is not known how this inflammation extends to or affects the ovary. Additionally, the relationship between ovulation and inflammation in PCOS is not well-defined. We hypothesize that the ovarian follicular immune environment in PCOS is uniquely dysregulated, and that resolving anovulation through ovulation induction is not sufficient to alleviate this dysregulation. Using single-cell RNA and surface protein analysis of peripheral blood and follicular fluid from patients undergoing in vitro fertilization, we discovered that both control and PCOS follicles were immunologically distinct from circulation. At a systemic level, we find that ovulation induction in PCOS does not alleviate systemic inflammation. In contrast, while healthy control ovaries experienced acute immune-directed ovulatory signaling, PCOS ovarian follicles were deficient in key pro-ovulatory cell to cell communication, and displayed instead a chronic low-grade inflammatory state with fibrotic features. Taken together, a picture emerges where acute ovulation demonstrates a well-ordered series of follicle-specific immune information flows, which are disrupted and replaced by low grade chronic inflammation in the PCOS follicle.
PMID:40832428 | PMC:PMC12363743 | DOI:10.1101/2025.08.11.25333027
Environ Sci Technol. 2025 Aug 19. doi: 10.1021/acs.est.5c07050. Online ahead of print.
ABSTRACT
Endocrine-disrupting chemicals (EDCs) pose significant health risks at environmentally relevant levels. Global screening efforts have predominantly relied on competitive binding assays. Here, using biochemical assays and computational simulations, we identified a crucial but largely overlooked noncompetitive binding mode between EDCs and the androgen receptor (AR). Two underappreciated sites within the AR ligand-binding domain, active function 2 (AF2) and binding function 3 (BF3), were found to influence AR activity and coregulator recruitment. Specifically, AF2-binders sterically obstruct coactivator docking, while BF3-binders indirectly weaken coactivator interactions via allosteric coupling. We show that these newly recognized surfaces hamper AR-driven transcription even in the presence of endogenous hormones. Expanding the regulatory landscape of AR beyond its conventional ligand-binding domain, we find that noncompetitive binding was prevalent among 7841 EDCs. Notably, the AF2 site emerged as a key hotspot, with median preference scores exceeding those of other sites by more than 3-fold among active EDCs. These findings challenge the current paradigm of EDC screening, underscore the need for broadened assay development, and pave the way for innovative methods tailored to noncompetitive mechanisms.
PMID:40828129 | DOI:10.1021/acs.est.5c07050
J Hazard Mater. 2025 Aug 15;497:139570. doi: 10.1016/j.jhazmat.2025.139570. Online ahead of print.
ABSTRACT
4-tert-Octylphenol (4t-OP) is an endocrine-disrupting chemical widely used in industrial products that exert neurotoxic effects, thus affecting hippocampal neurogenesis and cognitive function. However, its effect on the subventricular zone (SVZ), a crucial neurogenic niche, remains unclear. The present study demonstrated that maternal 4t-OP exposure significantly reduced neurogenesis in the dorsal SVZ, the primary source of dopaminergic periglomerular cells and superficial granule cells, in the olfactory bulb (OB) in mouse offspring. This reduction in neural progenitor populations led to decreased numbers of OB neurons, particularly tyrosine hydroxylase- and calretinin-positive cells, which play a key role in olfactory processing. These changes persisted in adulthood and were associated with olfactory dysfunction, including impaired odor detection and reduced social odor preference in behavioral tests. These findings indicate that 4t-OP exposure disrupts SVZ neurogenesis, leading to long-term sensory and behavioral deficits, highlighting its potential neurodevelopmental risks. Moreover, the observed impairment in olfactory function induced by 4t-OP exposure provides new insight into how endocrine-disrupting chemicals affect sensory organs.
PMID:40829387 | DOI:10.1016/j.jhazmat.2025.139570
Sage Open Pediatr. 2025 Aug 16;12:30502225251361989. doi: 10.1177/30502225251361989. eCollection 2025 Jan-Dec.
ABSTRACT
The development of pubertal characteristics may be influenced by exogenous factors, including endocrine disruptors. Phytoestrogens, plant-derived compounds with estrogenic activity, have been studied for their potential impact on pubertal timing. This scoping review assessed the available evidence on the association between dietary phytoestrogen consumption and early pubertal development. A systematic search of 5 databases identified 16 studies: 1 clinical trial, 3 experimental animal studies, and 12 observational studies. Study designs and methodological quality were heterogeneous. Prospective cohort studies, offering higher-quality evidence, reported an inverse association between phytoestrogen intake and early pubertal development, while cross-sectional studies of lower quality found a direct association. Although findings are inconsistent, the best-quality evidence suggests that phytoestrogen consumption may delay pubertal onset. Further research with robust designs and standardized measures is required to clarify this relationship.
PMID:40827262 | PMC:PMC12357998 | DOI:10.1177/30502225251361989
Chemosphere. 2025 Aug 18;386:144644. doi: 10.1016/j.chemosphere.2025.144644. Online ahead of print.
ABSTRACT
Polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants (POPs) used as flame retardants that pose interlinked environmental health challenges, making them an ideal focus for One Health assessment. This review synthesizes current scientific knowledge on PBDEs contamination based on a literature analysis of PubMed, Web of Science, Scopus, and Google Scholar databases. It examines shared contamination sources, exposure pathways, toxicological mechanisms, and intervention strategies. PBDEs exemplify the One Health paradigm through their ubiquitous anthropogenic sources, causing global environmental contamination across all health domains. Common exposure pathways (dietary intake, dust inhalation, and maternal transfer), create direct interface between human and wildlife health via contaminated environmental reservoirs. Across species, PBDEs have been linked to convergent toxicological outcomes, including endocrine disruption, neurodevelopmental deficits, reproductive impairments, and immunotoxicity, underscoring shared vulnerability patterns. Recent studies highlight the interaction between PBDEs and microplastics, which may enhance bioavailability and introduce novel exposure pathways. Vulnerable populations, notably children and pregnant women, face disproportionate risks requiring targeted interventions, including source control, advanced remediation technologies, and cross-sectoral surveillance systems. Despite regulatory progress, PBDEs remain a persistent global concern due to environmental persistence, continued emissions from legacy products, and emerging vectors such as microplastic-mediated transport. Addressing these challenges demands coordinated, cross-sectoral approaches that integrate environmental monitoring, transdisciplinary research, and harmonized regulatory frameworks. The One Health perspective offers a robust and holistic model for managing PBDEs and related POPs, emphasizing the urgency of collaborative solutions that recognize the intrinsic interconnectedness of human, animal, and ecosystem health in combating global contamination challenges.
PMID:40829294 | DOI:10.1016/j.chemosphere.2025.144644
Ecotoxicol Environ Saf. 2025 Aug 18;303:118891. doi: 10.1016/j.ecoenv.2025.118891. Online ahead of print.
ABSTRACT
Thyroid cancer (TC) is a common malignant tumor of the endocrine system, with a markedly higher incidence in females. While radiation exposure remains the only proven exogenous risk factor, growing evidence implicates environmental pollutants in TC pathogenesis. Polycyclic aromatic hydrocarbons (PAHs) are endocrine-disrupting chemicals with well-established carcinogenicity. However, epidemiological studies linking PAH exposure to TC risk are still insufficient. In this study, 116 patients with TC and 132 healthy adults were recruited in Guangdong Province, China, to assess the association between urinary concentrations of hydroxylated PAHs (OH-PAHs), thyroid-related hormone levels, and the risk of TC. The results identified 1-hydroxynaphthalene (1-OHN) and 2-hydroxynaphthalene (2-OHN) as dominant metabolites, with cases exhibiting significantly elevated 2 + 3-hydroxyfluorene (2 +3-OHF), 2 + 3-hydroxyphenanthrene (2 +3-OHPhe), 1 + 9-OHPhe, and 1-hydroxypyrene (1-OHP) concentrations, while controls showed higher 4-OHPhe levels. Quantile-based g-computation and Bayesian kernel machine regression models demonstrated a positive association between mixed exposure to OH-PAHs and both TC risk and serum free triiodothyronine (FT3) levels, with 2-OHN demonstrating primary contribution. FT3 and FT4 did not mediate the relationship between individual OH-PAH exposures and TC risk. Sex-stratified analysis revealed heightened female susceptibility even at low exposure levels. In the future, there is a need for more epidemiological and toxicological studies to investigate the causal and potential mechanisms underlying PAH exposure and TC risk.
PMID:40829277 | DOI:10.1016/j.ecoenv.2025.118891
Chemosphere. 2025 Aug 18;386:144644. doi: 10.1016/j.chemosphere.2025.144644. Online ahead of print.
ABSTRACT
Polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants (POPs) used as flame retardants that pose interlinked environmental health challenges, making them an ideal focus for One Health assessment. This review synthesizes current scientific knowledge on PBDEs contamination based on a literature analysis of PubMed, Web of Science, Scopus, and Google Scholar databases. It examines shared contamination sources, exposure pathways, toxicological mechanisms, and intervention strategies. PBDEs exemplify the One Health paradigm through their ubiquitous anthropogenic sources, causing global environmental contamination across all health domains. Common exposure pathways (dietary intake, dust inhalation, and maternal transfer), create direct interface between human and wildlife health via contaminated environmental reservoirs. Across species, PBDEs have been linked to convergent toxicological outcomes, including endocrine disruption, neurodevelopmental deficits, reproductive impairments, and immunotoxicity, underscoring shared vulnerability patterns. Recent studies highlight the interaction between PBDEs and microplastics, which may enhance bioavailability and introduce novel exposure pathways. Vulnerable populations, notably children and pregnant women, face disproportionate risks requiring targeted interventions, including source control, advanced remediation technologies, and cross-sectoral surveillance systems. Despite regulatory progress, PBDEs remain a persistent global concern due to environmental persistence, continued emissions from legacy products, and emerging vectors such as microplastic-mediated transport. Addressing these challenges demands coordinated, cross-sectoral approaches that integrate environmental monitoring, transdisciplinary research, and harmonized regulatory frameworks. The One Health perspective offers a robust and holistic model for managing PBDEs and related POPs, emphasizing the urgency of collaborative solutions that recognize the intrinsic interconnectedness of human, animal, and ecosystem health in combating global contamination challenges.
PMID:40829294 | DOI:10.1016/j.chemosphere.2025.144644
Fitoterapia. 2025 Aug 17;186:106822. doi: 10.1016/j.fitote.2025.106822. Online ahead of print.
ABSTRACT
Tanshinones (TS), bioactive lipophilic diterpenoids derived from Salvia miltiorrhiza(SM), demonstrate significant therapeutic promise for acne vulgaris (AV)-a multifactorial dermatosis characterized by P.acnes colonization, aberrant follicular keratinization, and immune-inflammatory cascades exacerbated by endocrine dysregulation and psychosocial stressors. This comprehensive review synthesizes recent advances elucidating TS's tripartite mechanistic framework: (1) Direct antibacterial activity against P. acnes and multidrug-resistant Staphylococcus aureus, disrupting biofilm formation and quorum sensing; (2) Immunomodulation via suppression of NLRP3 inflammasomes, inhibition of MAPK/NF-κB signaling pathways, and downregulation of pro-inflammatory cytokines; (3) Sebostatic and antioxidant effects through modulation of SREBP-1/FASN-mediated lipid biosynthesis, Nrf2/ARE pathway activation, SOD/COX-2 regulation, and potent ROS scavenging. Innovations in pharmaceutical engineering-including carrier-free self-assembled nanoparticles, autolytic microneedle arrays, photoactivated nanoemulsions, and chitosan-based nanoencapsulated gels-have markedly enhanced TS bioavailability, dermal retention, and pilosebaceous targeting. Clinical evaluations confirm TS formulations significantly reduce inflammatory lesion counts, acne recurrence rates, serum testosterone, and oxidative stress biomarkers. Synergistic regimens combining TS with photodynamic therapy, intense pulsed light, or conventional agents demonstrate enhanced anti-acne efficacy while minimizing cutaneous irritation. Despite promising outcomes, translational challenges persist, including pharmacokinetic limitations, clinical validation gaps in long-term safety, and scale-up complexities of advanced delivery systems. Future research should prioritize randomized multicenter trials, predictive ex vivo models, and hybrid delivery platforms to accelerate evidence-based integration into dermatological practice.
PMID:40829734 | DOI:10.1016/j.fitote.2025.106822
Environ Res. 2025 Aug 16:122621. doi: 10.1016/j.envres.2025.122621. Online ahead of print.
ABSTRACT
Plastics released into the environment inevitably degrade into microplastics, which subsequently enter the food web. As a result, humans are chronically exposed to microplastics through ingestion. However, studies evaluating the effects of environmentally derived microplastics are limited. This study aimed to elucidate the impact of subchronic exposure to environmentally sourced polyvinyl chloride (PVC) microplastics on mammalian intestinal tissue and gut microbiota. Microplastics were generated from cryoground environmental debris and consisted of irregularly shaped PVC fragments (45-100 μm), containing 16 additives, including 7 known endocrine disruptors. Mice were exposed to PVC-contaminated food (50 μg/g) for 26 days. Under steady-state conditions, PVC exposure increased molecular markers of inflammation and oxidative stress without inducing overt histomorphological alterations in the colon. In a model of chronic colitis, PVC exposure exacerbated clinical symptoms, histological damage, and molecular markers of inflammation and fibrosis. These effects were associated with increased recruitment of neutrophils to the colon. Correlation analyses revealed significant associations between colitis exacerbation and increased relative abundances of Gastranaerophilales, Parasutterella, Clostridium sensu stricto 1, Colidextribacter, and Dubosiella, alongside a reduction in Lactobacillus and an enrichment of the isopropanol biosynthesis pathway. These findings add to growing evidence that real-world microplastics, including non-spherical PVC fragments, can induce intestinal toxicity.
PMID:40825521 | DOI:10.1016/j.envres.2025.122621
Environ Sci Technol. 2025 Aug 18. doi: 10.1021/acs.est.5c07179. Online ahead of print.
ABSTRACT
The pervasive detection of trace 17β-estradiol (E2) in aquatic ecosystems necessitates innovative analytical platforms capable of ultrahigh sensitivity and field applicability. Herein, we report a nanofluidic biosensor integrating polydopamine-functionalized graphene oxide (PDA/GO) membranes with an entropy-driven DNA circuit and hyperbranched DNA nanowires (HDW) for femtomolar-level E2 quantification. Leveraging E2-specific aptamer recognition, the system triggers an entropy-driven DNA circuit and subsequent hierarchical assembly of guanine quadruplex (G4)-enriched HDW nanostructures on nanochannel surfaces, amplifying interfacial electronegativity through phosphate backbone accumulation. This charge amplification synergizes with subnanometer-confined ion transport modulation, achieving an 8.19-fold current enhancement upon E2 binding. The optimized biosensor exhibited a linear dynamic range spanning five orders (1 fM to 100 pM) with a detection limit of 0.39 fM, comparable to conventional LC-MS/MS for the analysis of E2. Rigorous specificity testing demonstrated high anti-interference against structural analogs and endocrine disruptors. Practical validation in real water samples (Yellow River, Heihu Spring, Qian Lake, and an aquaculture pond) demonstrated recovery rates of 91.2-109%, supported by robust stability and environmental resilience. This work establishes nucleic acid nanotechnology-enhanced nanofluidics, addressing critical gaps in on-site endocrine disruptor monitoring through synergistic molecular recognition and interfacial charge engineering.
PMID:40825210 | DOI:10.1021/acs.est.5c07179
Environ Pollut. 2025 Aug 16:127000. doi: 10.1016/j.envpol.2025.127000. Online ahead of print.
ABSTRACT
Bisphenol AF (BPAF), a substitute for bisphenol A (BPA), is frequently found in the environment and daily necessities and has garnered significant attention due to its endocrine-disrupting effects. Uterus is a potential target of BPA while more evidences about BPAF are needed, especially at human-relevant levels. The aim of this study was to determine the effects of BPAF exposure with realistic human exposure pathway and dosage on the uterus, as well as to explore its molecular mechanisms through transcriptome sequencing (RNA-seq) and alternative splicing (AS) analysis. Female CD-1 mice were continuously exposed to BPAF levels of 30, 300, and 3000 μg/kg/day for six weeks through diet. Following euthanasia, blood and uterus were collected. The results showed that mice in BPAF exposure group exhibited symptoms of endometrial hyperplasia in the uterus, characterized by thickening of the endometrium. In addition, BPAF exposure altered the levels of nine hormones, including pregnenolone, androsterone, estrone, testosterone and so on, and led to prolonged estrus cycle. Transcriptomic analysis revealed a significant disruption in the balance of extracellular matrix (ECM) and humoral immune biological processes, to which matrix metallopeptidase 7 (Mmp7) and indian hedgehog (Ihh) were identified as key genes related. Additionally, AS analysis indicated intron retention occurred in collagen type I alpha 2 chain (Col1a2), which resulted in a protein structure alternation and further led to uterine abnormality. These findings suggest that BPAF exposure at relatively low levels disturbs the balance of the extracellular matrix and the immune system in the uterus. Considering that there are currently only toxicity limits for BPA, our study provides data reference for the toxicological evaluation and threshold setting of BPA substitute, and provides a new research paradigm for the progress of related toxicology research.
PMID:40825420 | DOI:10.1016/j.envpol.2025.127000
Environ Res. 2025 Aug 16:122621. doi: 10.1016/j.envres.2025.122621. Online ahead of print.
ABSTRACT
Plastics released into the environment inevitably degrade into microplastics, which subsequently enter the food web. As a result, humans are chronically exposed to microplastics through ingestion. However, studies evaluating the effects of environmentally derived microplastics are limited. This study aimed to elucidate the impact of subchronic exposure to environmentally sourced polyvinyl chloride (PVC) microplastics on mammalian intestinal tissue and gut microbiota. Microplastics were generated from cryoground environmental debris and consisted of irregularly shaped PVC fragments (45-100 μm), containing 16 additives, including 7 known endocrine disruptors. Mice were exposed to PVC-contaminated food (50 μg/g) for 26 days. Under steady-state conditions, PVC exposure increased molecular markers of inflammation and oxidative stress without inducing overt histomorphological alterations in the colon. In a model of chronic colitis, PVC exposure exacerbated clinical symptoms, histological damage, and molecular markers of inflammation and fibrosis. These effects were associated with increased recruitment of neutrophils to the colon. Correlation analyses revealed significant associations between colitis exacerbation and increased relative abundances of Gastranaerophilales, Parasutterella, Clostridium sensu stricto 1, Colidextribacter, and Dubosiella, alongside a reduction in Lactobacillus and an enrichment of the isopropanol biosynthesis pathway. These findings add to growing evidence that real-world microplastics, including non-spherical PVC fragments, can induce intestinal toxicity.
PMID:40825521 | DOI:10.1016/j.envres.2025.122621
Environ Health. 2025 Aug 18;24(1):57. doi: 10.1186/s12940-025-01202-6.
ABSTRACT
BACKGROUND: With daily exposure to multiple endocrine disrupting chemicals (EDCs), understanding individualized co-exposure patterns could better identify chemicals that threaten health. This is particularly pertinent for the vulnerable fetus during in-utero development, where exposure can have long lasting health consequences. As there is limited information of EDC exposure in Asian maternal-offspring populations, this study aimed to (1) determine levels of a selected range of EDCs (focusing on Substances of Very High Concern by the European Chemical Agency) in maternal and corresponding cord blood plasma, (2) investigate the sociodemographic factors associated with plasma EDC concentrations, and (3) associate EDC-mixtures with birthweight, in a Singapore cohort.
METHODS: Targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine the concentration of 30 chemicals of interest in 780 maternal and 782 cord plasma samples collected at delivery in the multi-ethnic Asian (Chinese, Malay, Indian) mother-offspring GUSTO study. Quantile-based g-computation was used to estimate the combined effect of chemical mixtures and its association with birthweight.
RESULTS: Twenty-seven out of the thirty selected chemicals were reliably detected in both maternal and cord plasma. Perfluorooctanesulfonic, perfluorooctanoic, perfluorobutanesulfonic and perfluorobutanoic acids (PFOS, PFOA, PFBS, PFBA, respectively) were the predominant perfluoroalkyl acids (detected in > 90% of samples), while mono (2-ethylhexyl) phthalate (MEHP) and monobutyl phthalate were the main phthalate metabolites (detected in > 99% of samples). Concentrations of fourteen chemicals, including PFBA, PFBS and bisphenol S (BPS) were higher in cord plasma than in corresponding maternal plasma; eight being > 1.5 times higher (ranging from 1.75 to 2.93). A mixture of chemicals in cord plasma associated with higher birthweight [116.5 g (95%CI 3.1, 229.9) per quantile increase], but no association was observed for the maternal mixture. Further, different chemicals from the same EDC group in either cord or maternal plasma showed associations in opposite directions with birthweight.
DISCUSSION: Our results suggest substantial transplacental transfer and fetal accumulation of many chemicals, particularly the newer replacement compounds. Stronger associations with birthweight were found for the cord chemical mixture than for the maternal mixture, supporting the idea that these chemicals may have direct effects in the fetus to influence growth. Moreover, individual chemicals within each EDC group appear to have different mechanisms of effect resulting in divergent associations with birthweight.
CONCLUSION: This study adds to the growing concern about the impact of EDCs, especially the newer chemicals on vulnerable groups such as the developing fetus, warranting further research on the potential effects of in-utero EDC exposure on child health.
PMID:40826080 | PMC:PMC12363001 | DOI:10.1186/s12940-025-01202-6
Front Public Health. 2025 Aug 1;13:1568140. doi: 10.3389/fpubh.2025.1568140. eCollection 2025.
ABSTRACT
Cleft lip and palate (CLP) is a prevalent congenital anomaly of the maxillofacial region, characterized by abnormal openings in the lip or palate. This condition, affecting approximately 1 in 700 newborns globally, can manifest as cleft lip only, cleft palate only, or both. The etiology of CLP remains multifactorial, involving genetic and environmental influences, with maternal systemic diseases during pregnancy emerging as significant risk factors. Conditions such as circulatory disorders, endocrine and metabolic disorders, infectious diseases, and autoimmune diseases have been associated with increased CLP incidence. These maternal health issues can disrupt normal embryonic development, leading to cleft formation and affecting the child's overall wellbeing, including feeding, speech, dental health, and psychological state. This review explores the relationship between maternal systemic diseases, including circulatory, endocrine and metabolic, infectious, and autoimmune disorders, and the occurrence of CLP in newborns. Understanding these connections is crucial for improving maternal health during pregnancy and reducing the risk of CLP, highlighting the importance of early monitoring and intervention.
PMID:40823220 | PMC:PMC12354372 | DOI:10.3389/fpubh.2025.1568140
Environ Toxicol Chem. 2025 Aug 18:vgaf210. doi: 10.1093/etojnl/vgaf210. Online ahead of print.
ABSTRACT
Phthalates are high production synthetic compounds primarily used as plasticizers in plastic products to help with manufactured substance flexibility, pliability, and reduce environmental degradation. Phthalates have been detected in various manufactured goods ranging from food packaging to personal care products to water bottles. Unfortunately, recent studies have shown evidence of endocrine disruption and adverse effects upon reproductive systems following phthalate exposure in both males and females. This study aimed to quantify phthalate residues that leached from polyethylene terephthalate (PET) bottles into drinking water over a 35-d period placed either in an indoor UV chamber or outside. Using gas chromatography/mass spectrometry (GC/MS) coupled with direct immersion solid phase microextraction (SPME) fibers, the highest total phthalate concentration in bottles exposed indoors was 451 ± 366.5 µg/L with butyl benzyl phthalate (BBP) concentrations being the highest individual concentration (297.6 ± 284.3 µg/L). In the outdoor exposure group, the highest total phthalate concentration was 546.7 ± 217.5 µg/L, with BBP being at the highest concentration (395.4 ± 189.3 µg/L). A subsequent risk assessment was conducted quantifying the risk associated with adults consuming leachate found in bottled water in various countries across North America, Asia, and Europe. Using standard reference values and experimental values expressed here, it was found that there was no calculated risk associated with consuming this bottled water.
PMID:40824283 | DOI:10.1093/etojnl/vgaf210
Environ Res. 2025 Aug 15;285(Pt 5):122620. doi: 10.1016/j.envres.2025.122620. Online ahead of print.
ABSTRACT
The neonicotinoid imidacloprid (IMI) is used worldwide for insect control and represents a potential risk to populations, due to its potential action as an endocrine disruptor (ED). IMI binds to the postsynaptic nicotinic acetylcholine receptor (nAChR), whereas other neonicotinoids can activate the G protein-coupled estrogen receptor (GPER). Here, we examined the IMI effect on the mammary gland in a peripuberal model where female mice were exposed to IMI (0.01, 0.1 and 10 mg/kg/day). Alterations observed in the mammary morphology included an increase in transverse ductal growth at 0.1 and 10 mg/kg/day and a reduction in branch density at 0.1 mg/kg/day. Furthermore, 10 mg/kg/day IMI increased the number of terminal end buds (TEBs), induced ductal hyperplasia and epithelial cell proliferation. In mammary epithelial NMuMG cells, IMI (0.01-10 μM) showed no cytotoxic effect but boosted clonogenic capacity at 0.1 and 1 μM. Western blot findings revealed that 1 and 10 μM IMI rises GPER and aromatase expression, but declines progesterone receptor levels at all assayed doses. IMI (10 μM) also increased α7-nAChR expression at 24 h and induced c-Src phosphorylation after 1 h of treatment. Finally, 10 μM IMI promoted cell migration and the proteolytic activity of metalloproteinase (MMP)-2 and -9 through GPER, α7-nAChR, and c-Src. In summary, IMI promotes preneoplastic lesions and TEBs retention and increases mammary epithelial cell motility through GPER and α7-nAChR. Our results support the hypothesis that IMI acts as an ED, affecting mammary gland structure.
PMID:40819670 | DOI:10.1016/j.envres.2025.122620
J Food Prot. 2025 Aug 15:100600. doi: 10.1016/j.jfp.2025.100600. Online ahead of print.
ABSTRACT
Mycotoxins, such as aflatoxins (AFs), deoxynivalenol (DON), zearalenone (ZEN), and ochratoxin A (OTA), present significant health risks due to their carcinogenic and toxic properties. This study conducted a systematic review and meta-analysis to assess the global prevalence, concentration, and associated health risks of mycotoxins in domestic bird eggs. Following the PRISMA guideline, a comprehensive search was performed across PubMed, Scopus, and Web of Science (2005-2024). Thirteen studies, encompassing 8,410 egg samples, were analyzed. The pooled prevalence and concentration of mycotoxins were estimated using random-effects models, while probabilistic risk assessment was performed via Monte Carlo simulation, calculating the Margin of Exposure (MOEs) and Hazard Quotient (HQ). The prevalence ranking of aflatoxins (AFs) in eggs was as follows: AFB1 (19%) > AFB2 (12%) > AFG1 (10%) ≈ AFG2 (10%). In terms of mean pooled concentration, mycotoxins followed this order: DON (83.93 µg/kg) > ZEN (6.00 µg/kg) > AFs (5.604 µg/kg) > OTA (2.52 µg/kg). Concentrations of DON and OTA were higher in egg white than in yolk, whereas ZEN levels were higher in yolk. From a public health perspective, risk assessment revealed alarming exposure levels, particularly in China, Egypt, and Jordan, where MOEs values for AFB1 were significantly below the safety threshold (MOEs < 10,000). Children were found to be at heightened risk due to their lower body weight and developing physiological systems, with MOEs as low as 3 in China. Additionally, HQ analyses indicated non-negligible risks from DON, OTA, and ZEN, particularly in China and Poland, where dietary exposure may contribute to chronic toxicity or endocrine disruption.
PMID:40819745 | DOI:10.1016/j.jfp.2025.100600
Cardiovasc Toxicol. 2025 Aug 17. doi: 10.1007/s12012-025-10054-y. Online ahead of print.
ABSTRACT
Endocrine disrupting chemicals (EDCs) are exogenous compounds that interfere with the normal functioning of the endocrine system. This effect is crucial for maintaining hormonal balance and regulating various physiological processes. Phthalates, parabens, and triclosan are EDCs found in many personal care products (make-up, shampoo, perfume, shaving foam, moisturizing cream, hair dyes, deodorant), plastics, pesticides, pharmaceuticals, and household cleaning products, and can be inhaled or absorbed by the body through inhalation or skin contact. Atherosclerosis is a major cause of cardiovascular diseases, including coronary artery disease, stroke, and peripheral artery disease. While traditional risk factors for atherosclerosis, such as high cholesterol, hypertension, and smoking, have been extensively studied, emerging evidence suggests that EDCs may also play a significant role in the development and progression of atherosclerosis. Several potential mechanisms have been proposed to explain how EDCs contribute to atherosclerosis. One mechanism involves the activation of nuclear receptors, such as peroxisome proliferator-activated receptors (PPARs) and estrogen receptors (ERs), by EDCs. Activation of these receptors can lead to dysregulation of lipid metabolism, inflammation, and oxidative stress, all of which are key processes in atherosclerosis development. EDCs have been shown to disrupt endothelial function through various mechanisms. Some of these mechanisms are the formation of reactive oxygen species (ROS) and free oxygen radicals, and impaired nitric oxide (NO) production by EDCs. This literature review aims to explore the current understanding of the role of EDCs in atherosclerosis.
PMID:40820178 | DOI:10.1007/s12012-025-10054-y
Environ Sci Technol. 2025 Aug 16. doi: 10.1021/acs.est.5c07018. Online ahead of print.
ABSTRACT
Bisphenol A (BPA) is a well-known endocrine disruptor linked to numerous adverse health outcomes and was, therefore, banned in food-contact materials in the European Union. Numerous alternatives are now in commerce, but their health hazards are often inadequately addressed. This study compared BPA and 26 alternatives in six in vitro bioassays for cytotoxicity, endocrine disruption, xenobiotic metabolism, adaptive stress responses, mitochondrial toxicity, and neurotoxicity. We developed a cumulative specificity ratio score that integrates the degree of specific activation and overall toxicological activity across a test battery, enabling direct comparison of BPA with its alternatives. Several alternatives with close structural resemblance showed similar or stronger activation of the estrogen receptor α (ERα) than BPA. The lack of estrogenicity for several BPA alternatives, e.g., 4-(4-phenylmethoxyphenyl)sulfonylphenol (BPS-MPE), was accompanied by a shift toward peroxisome proliferator-activated receptor γ (PPARγ) activation, a receptor that is not relevant for BPA itself. Some alternatives additionally inhibited mitochondrial functions and caused neurotoxicity. Simulated phase I metabolism reduced the cytotoxicity of all alternatives except for methyl bis(4-hydroxyphenyl)acetate (Bz) and 4-[[4-(allyloxy)phenyl]sulfonyl]phenol (BPS-MAE), while estrogenic activity remained unchanged or decreased. This study demonstrates the utility of bioassays for rapid hazard assessment and comparative evaluation, suggesting that many BPA alternatives are regrettable substitutes, although 2,2,4,4-tetramethyl-1,3-cyclobutanediol (TMCD) is a potentially more benign alternative.
PMID:40817891 | DOI:10.1021/acs.est.5c07018
Proc Natl Acad Sci U S A. 2025 Aug 19;122(33):e2507571122. doi: 10.1073/pnas.2507571122. Epub 2025 Aug 15.
ABSTRACT
While Estrogen receptor alpha (ERα)+ breast cancer treatment is considered effective, resistance to endocrine therapy is common. Since ERα is still the main driver in most therapy-resistant tumors, alternative therapeutic strategies are needed to disrupt ERα transcriptional activity. In this work, we position TRIM24 as a therapeutic target in endocrine resistance, given its role as a key component of the ERα transcriptional complex. TRIM24 interacts with ERα and other well-known ERα cofactors to facilitate ERα chromatin interactions and allows for maintenance of active histone marks including H3K23ac and H3K27ac. Consequently, genetic perturbation of TRIM24 abrogates ERα-driven transcriptional programs and reduces tumor cell proliferation capacity. Using a recently developed degrader targeting TRIM24, ERα-driven transcriptional output and growth were blocked, effectively treating not only endocrine-responsive cell lines but also drug-resistant derivatives thereof as well as cell line models bearing activating ESR1 point mutations. Finally, using human tumor-derived organoid models, we could show the efficacy of TRIM24 degrader in the endocrine-responsive and -resistant setting. Overall, our study positions TRIM24 as a central component for the integrity and activity of the ERα transcriptional complex, with degradation-mediated perturbation of TRIM24 as a promising therapeutic avenue in the treatment of primary and endocrine resistance breast cancer.
PMID:40815626 | DOI:10.1073/pnas.2507571122
Environ Int. 2025 Aug 11;203:109723. doi: 10.1016/j.envint.2025.109723. Online ahead of print.
ABSTRACT
OBJECTIVE: Upon exposure, persistent organic pollutants (POPs) accumulate in the body. One-time point measurement of POPs plasma concentrations can reflect body burden. This study aimed to assess whether maternal factors including age, breastfeeding, and weight, influence changes in plasma concentrations of POPs in women during critical periods of physical changes from pregnancy to 15-60 months after delivery.
METHODS: Ninety-nine self-identified Hispanic women who were diagnosed with gestational diabetes mellitus (GDM) and originally enrolled in the GDM cohort study in 1993-1995 were included in this study. Plasma concentrations of 21 polychlorinated biphenyls (PCBs), 7 organochlorine pesticides (OCPs), 5 polybrominated diphenyl ethers (PBDEs), 2,2',4,4',5,5'-hexabromobiphenyl (BB153), and 6 per- and polyfluoroalkyl substances (PFAS) were quantified in archived samples collected in the 3rd trimester of pregnancy and post-delivery (81.8 % were from 15 months after delivery, the rest were from 30-60 months post-delivery). Multivariable linear regression was used to analyze associations of maternal factors such as weight change, age and breastfeeding status after delivery with changes in POPs concentrations from 3rd trimester of pregnancy to the post-delivery visit.
RESULTS: From pregnancy to post-delivery period, plasma concentrations of 4 PBDEs and 6 PFAS significantly increased, while those of 20 PCBs, all OCPs and BB153 significantly decreased (all p-values < 0.05). Additionally, older age and breastfeeding after delivery were significantly associated with greater reduction in concentrations of PCBs, OCPs, and BB153 from pregnancy to the post-delivery period, whereas weight loss was associated with a smaller reduction in these POPs (all p-values < 0.05). Post-delivery weight gain was associated with greater elevation in concentrations of 2-(N-methylperfluorooctane sulfonamido) acetate and branched isomers of perfluorooctane sulfonate.
CONCLUSION: Concentrations of PCBs, OCPs, and BB153 declined more in older women and those who breastfed their newborns, whereas the decline was smaller among women who lost more weight after delivery.
PMID:40816047 | DOI:10.1016/j.envint.2025.109723
mSystems. 2025 Aug 15:e0087925. doi: 10.1128/msystems.00879-25. Online ahead of print.
ABSTRACT
Gut microbiota and systemic metabolites are critical for breast cancer progression and therapeutic response. This study investigated gut microbiota and metabolic profiles of breast cancer patients before and after adjuvant endocrine therapy (AET). Using 16S rRNA sequencing and untargeted metabolomics, we identified significant disruptions in microbial diversity and metabolic pathways. Alpha diversity was reduced in pre-AET patients, with partial restoration observed post-AET. Key genera, such as Bifidobacterium and Coprococcus, were enriched in pre-AET patients, whereas Proteus and Methylobacterium were enriched in post-AET patients. Metabolomic analysis revealed significant reductions in the levels of vitamin B6 metabolites in both the pre-AET and post-AET groups compared to those in the healthy control (HC) group, indicating potential nutrient deficiencies or metabolic stress. Elevated cholesterol and estrogen metabolite levels in pre-AET patients reflect dysregulated lipid and hormone metabolism, with post-AET decreases in estrogen metabolites, confirming therapeutic efficacy. Correlation analysis revealed that Klebsiella_724518 was positively correlated with estrogen and vitamin B6 metabolites, whereas Proteus, Methylobacterium, Treponema_D, and Holdemanella were negatively correlated with cholesterol. Receiver operating characteristic (ROC) curve analysis identified estriol (area under the curve [AUC] = 1.000) as a strong diagnostic biomarker for distinguishing HCs from pre-AET patients, whereas cholesterol (AUC = 0.880) and estradiol-17β (AUC = 0.870) were highly effective in monitoring the therapeutic response to AET. This study highlights the role of gut microbiota and its metabolic byproducts in breast cancer development and treatment outcomes. It also reveals promising microbial and metabolite signatures for non-invasive cancer detection, tracking progression, and monitoring treatment response.IMPORTANCEBreast cancer progression and treatment response remain challenging to predict and monitor effectively. Our findings demonstrate the dual role of the gut microbiota and its metabolic products in influencing both. Strong correlations between specific microbial taxa and key metabolites provide new mechanistic insights into the influence of gut microbes on therapeutic outcomes during endocrine therapy. Importantly, we identified high-performance biomarkers, with estriol showing perfect diagnostic accuracy (AUC = 1.000) and cholesterol effectively monitoring treatment response (AUC = 0.880), highlighting their potential for non-invasive clinical applications. This study provides a foundation for applying gut microbiome research to develop clinical tools that could improve breast cancer management.
PMID:40815148 | DOI:10.1128/msystems.00879-25
Environ Int. 2025 Aug 11;203:109725. doi: 10.1016/j.envint.2025.109725. Online ahead of print.
ABSTRACT
Exposure to multiple endocrine-disrupting chemicals (EDCs) may have some adverse impacts on child health; yet, little data is available on the body burdens, co-exposure patterns, health risks, and possible sources of a broad range of EDCs in school-age children. A total of 33 chemicals including 3 non-specific pyrethroid pesticide metabolites, 2 specific organophosphorus pesticide metabolites, 5 chlorophenols, 4 phenols, 5 parabens and 14 toxic and essential elements were quantified in urine. A 24-hour dietary recall survey was conducted to collect dietary information, and seven food categories were classified accordingly. Multivariable linear regression models were applied to estimate associations of dietary information and drinking water types with urinary EDC concentrations. A total of 31 chemicals were detected in more than 50 % of urinary samples. The number of 10 (2.44 %), 32 (7.80 %), 4 (0.98 %), 20 (4.88 %), and 3 (0.73 %) children who experienced exposure levels of over 75th percentiles was found, for pesticides, phenols, parabens, selected toxic elements and these chemical mixtures, respectively. The consumption of dairy products was positively associated with urinary 2,4,6-trichlorophenol concentrations. Meat and meat products and vegetable consumption predicted higher urinary concentrations of methyl- and ethyl-paraben, respectively. Cereal intakes were positively associated with urinary cadmium, arsenic and cobalt levels, and the consumption of aquatic products was in relation to increases of urinary lead and cadmium concentrations. Children who mainly drank filtered water had lower urinary concentrations of chlorpyrifos metabolite and bisphenol A, while those with bottled water as the main drinking water source had higher 2,4-dichlorophenol concentrations and lower selenium levels in urine, compared to those who mainly drank tap water. Our findings suggested that children in this area were widely exposed to multiple classes of EDCs, and diet and drinking water were potential exposure sources of the analyzed chemicals.
PMID:40816046 | DOI:10.1016/j.envint.2025.109725
Environ Int. 2025 Aug 11;203:109723. doi: 10.1016/j.envint.2025.109723. Online ahead of print.
ABSTRACT
OBJECTIVE: Upon exposure, persistent organic pollutants (POPs) accumulate in the body. One-time point measurement of POPs plasma concentrations can reflect body burden. This study aimed to assess whether maternal factors including age, breastfeeding, and weight, influence changes in plasma concentrations of POPs in women during critical periods of physical changes from pregnancy to 15-60 months after delivery.
METHODS: Ninety-nine self-identified Hispanic women who were diagnosed with gestational diabetes mellitus (GDM) and originally enrolled in the GDM cohort study in 1993-1995 were included in this study. Plasma concentrations of 21 polychlorinated biphenyls (PCBs), 7 organochlorine pesticides (OCPs), 5 polybrominated diphenyl ethers (PBDEs), 2,2',4,4',5,5'-hexabromobiphenyl (BB153), and 6 per- and polyfluoroalkyl substances (PFAS) were quantified in archived samples collected in the 3rd trimester of pregnancy and post-delivery (81.8 % were from 15 months after delivery, the rest were from 30-60 months post-delivery). Multivariable linear regression was used to analyze associations of maternal factors such as weight change, age and breastfeeding status after delivery with changes in POPs concentrations from 3rd trimester of pregnancy to the post-delivery visit.
RESULTS: From pregnancy to post-delivery period, plasma concentrations of 4 PBDEs and 6 PFAS significantly increased, while those of 20 PCBs, all OCPs and BB153 significantly decreased (all p-values < 0.05). Additionally, older age and breastfeeding after delivery were significantly associated with greater reduction in concentrations of PCBs, OCPs, and BB153 from pregnancy to the post-delivery period, whereas weight loss was associated with a smaller reduction in these POPs (all p-values < 0.05). Post-delivery weight gain was associated with greater elevation in concentrations of 2-(N-methylperfluorooctane sulfonamido) acetate and branched isomers of perfluorooctane sulfonate.
CONCLUSION: Concentrations of PCBs, OCPs, and BB153 declined more in older women and those who breastfed their newborns, whereas the decline was smaller among women who lost more weight after delivery.
PMID:40816047 | DOI:10.1016/j.envint.2025.109723
Mar Pollut Bull. 2025 Aug 14;221:118570. doi: 10.1016/j.marpolbul.2025.118570. Online ahead of print.
ABSTRACT
Dibutyl phthalate (DBP), a prevalent industrial plasticizer, can infiltrate various aquatic environments due to plastic pollution. The current knowledge on the effects of DBP on marine micro-invertebrates is still relatively scarce. In this study, we investigated the ecological risks and toxicity mechanisms of 0-4.01 mg/L DBP on the marine rotifer Brachionus plicatilis at the population, individual, biochemical, and molecular levels. The 24 h-LC50 value of DBP against B. plicatilis is 8.02 mg/L, indicating significant ecological risks DBP poses. Furthermore, DBP exposure led to reduced individual and egg size, increased offspring production, extended lifespan, and altered feeding behavior in rotifers. Faster growth of rotifer populations in the 0.80 mg/L DBP-exposed group. This suggests DBP may significantly influence the stability of zooplankton community structures at lower concentrations (≤ 0.80 mg/L). DBP at 4.01 mg/L resulted in a significant decrease in the feeding rate of rotifers and caused glutathione cycle activation, oxidative stress, apoptosis, and neurological damage at the molecular level. These findings suggest that prolonged exposure to high levels of DBP adversely affects rotifers, ultimately leading to a slowdown in population growth. Moreover, DBP regulates nitric oxide production by binding to estrogen receptors, ultimately affecting rotifers' reproductive capacity. This study highlights the impact of endocrine disruptors on the survival and reproduction of marine invertebrates.
PMID:40816120 | DOI:10.1016/j.marpolbul.2025.118570
Ecotoxicol Environ Saf. 2025 Aug 14;303:118874. doi: 10.1016/j.ecoenv.2025.118874. Online ahead of print.
ABSTRACT
Breast cancer is a leading cause of death in women worldwide. Data suggests that hereditary factors only account for 5-10 % of breast cancer incidence, resulting in increased concern regarding the carcinogenicity involved with environmental and lifestyle-related factors. Among these, phthalates - ubiquitous endocrine disrupting chemicals founds in plastics, cosmetics, and food packaging - pose a growing concern. Human exposure to phthalates occurs through ingestion, inhalation, dermal contact, and critical windows such as intrauterine development. As an endocrine-responsive organ, the breast is particularly susceptible to disruption by these compounds. This review highlights emerging evidence linking phthalate exposure to the initiation, progression, and metastasis of breast cancer. This comprehensive overview of carcinogenesis-promoting mechanisms of phthalates, involving estrogen receptor signaling, oncogenic pathway activation, promotion of cancer stemness, and induction of therapy resistance, will provide crucial insights into phthalate-driven mechanisms in breast cancer that can inform future research directions, public health strategies, and regulatory efforts aimed at mitigating environmental cancer risks.
PMID:40816212 | DOI:10.1016/j.ecoenv.2025.118874
Aquat Toxicol. 2025 Aug 5;287:107528. doi: 10.1016/j.aquatox.2025.107528. Online ahead of print.
ABSTRACT
Ocean warming and acidification are climate change related drivers that impact the physiology of marine organisms and their ability to cope with future environments. Marine ecosystems are also facing pollution from an ever-growing diversity of chemical contaminants, including endocrine disruptors. A common example is the 17α-ethynylestradiol (EE2), which can affect the endocrine regulation of fish and hence potentially impact their fitness. Thus, fish have to cope to multiple climatic and chemical stresses that can interact, influencing the overall impact on fish physiology. In this study, we investigated whether the direct and carry-over effect of early exposure to EE2 (15 ng.L-1; one month during embryo-larval development) are modulated by the RCP8.5 scenario (+3°C; -0.4 pH unit). Five months post-contamination, we measured survival, growth and reproductive axis of prepubertal sticklebacks. Our findings revealed that the survival of juveniles, when exposed to EE2 during early development, is reduced under Current but not RCP8.5 scenario. Furthermore, under RCP8.5-EE2, a significantly lower body length was observed. Sex and tissue specific responses in terms of the expression profiles of genes related to development and sexual maturation was reported. Interestingly, significant interaction between RCP8.5 and EE2 was observed for the expression of ovarian aromatase (cyp19a1a), suggesting a long-lasting estrogenic effect under RCP8.5 scenario. Additionally, the skewed sex ratios and the presence of intersex individuals in both scenarios early exposed to EE2 suggested a feminization due to EE2, which could potentially disrupt sexual maturation and future reproduction. Hence, the early EE2 exposure had carry-over physiological effects on sticklebacks, and these effects can be modulated by the climate scenario. This underscores the importance of conducting long-term multi-stress studies to comprehensively understand the vulnerability on fish populations in future environments.
PMID:40816007 | DOI:10.1016/j.aquatox.2025.107528
Int J Mol Sci. 2025 Jul 28;26(15):7289. doi: 10.3390/ijms26157289.
ABSTRACT
Tetrabromobisphenol A (TBBPA) is a brominated flame retardant widely used in consumer products. TBBPA is often detected in soil, water, organisms, and even in human blood and breast milk. Hence, it is accessible to developing fetuses and nursing offspring after maternal exposure. The reported evidence for the endocrine disruption of TBBPA in the brain has raised concerns regarding its effects on neurodevelopmental and behavioral functions. This study investigated the effects of TBBPA exposure on neurodevelopment. A cell-based developmental neurotoxicity assay was performed to determine whether TBBPA is a developmental neurotoxicant. The assay revealed TBBPA to be a developmental neurotoxicant. C57BL/6N maternal mice were administered TBBPA at 0, 0.24, and 2.4 mg/kg during pregnancy and lactation, and their offspring underwent behavioral testing. The behavioral experiments revealed sex-specific effects. In females, only a deterioration of the motor ability was observed. In contrast, deteriorations in motor function, memory, and social interaction were noted in males. Furthermore, we validated changes in the expression of genes associated with behavioral abnormalities, confirming that perinatal exposure to TBBPA, at the administered doses, can affect neurodevelopment and behavior in offspring. These findings highlight the need for more in-depth and multifaceted research on the toxicity of TBBPA.
PMID:40806421 | PMC:PMC12346716 | DOI:10.3390/ijms26157289
Int J Mol Sci. 2025 Jul 25;26(15):7207. doi: 10.3390/ijms26157207.
ABSTRACT
Plastic pollution has recently become a serious environmental problem, since the continuous increase in plastic production and use has generated enormous amounts of plastic waste that decomposes to form micro- and nanoparticles (MPs/NPs). Recent evidence suggests that nanoplastics may be potent toxins because they are able to freely cross biological barriers, posing health risks, particularly to developing organisms. Therefore, the aim of the current study was to investigate the toxic potential of polystyrene nanoparticles (PS-NPs) on the jejunum of immature rats. Two-week-old animals were orally exposed to environmentally relevant dose of small PS-NPs (1 mg/kg b.w.; 25 nm) for 3 weeks. We detected a significant accumulation of PS-NPs in the epithelium and subepithelial layer of the intestine, which resulted in significant changes in the expression of genes related to gut barrier integrity, nutrient absorption, and endocrine function. Moreover, increased expression of proinflammatory cytokines was observed together with decreased antioxidant capacity and increased markers of oxidative damage to proteins. Additionally, in the jejunal extracts of exposed rats, we also noted changes in the metabolite profile, mainly amino acids involved in molecular pathways related to cellular energy, inflammation, the intestinal barrier, and protein synthesis, which were consistent with the observed molecular markers of inflammation and oxidative stress. Taken together, the results of the metabolomic, molecular, and biochemical analyses indicate that prolonged exposure to PS-NPs may disrupt the proper function of the intestine of developing organisms.
PMID:40806334 | PMC:PMC12346606 | DOI:10.3390/ijms26157207
Int J Mol Sci. 2025 Aug 4;26(15):7526. doi: 10.3390/ijms26157526.
ABSTRACT
Bisphenol A (BPA), a prevalent endocrine-disrupting chemical, is widely found in various consumer products and poses significant health risks, particularly through hormone receptor interactions, oxidative stress, and mitochondrial dysfunction. BPA exposure is associated with reproductive, metabolic, and neurodevelopmental disorders. Melatonin, a neurohormone with strong antioxidant and anti-inflammatory properties, has emerged as a potential therapeutic agent to counteract the toxic effects of BPA. This review consolidates recent findings from in vitro and animal/preclinical studies, highlighting melatonin's protective mechanisms against BPA-induced toxicity. These include its capacity to reduce oxidative stress, restore mitochondrial function, modulate inflammatory responses, and protect against DNA damage. In animal models, melatonin also mitigates reproductive toxicity, enhances fertility parameters, and reduces histopathological damage. Melatonin's ability to regulate endoplasmic reticulum (ER) stress and cell death pathways underscores its multifaceted protective role. Despite promising preclinical results, human clinical trials are needed to validate these findings and establish optimal dosages, treatment durations, and safety profiles. This review discusses the wide range of potential uses of melatonin for treating BPA toxicity and suggests directions for future research.
PMID:40806654 | PMC:PMC12347934 | DOI:10.3390/ijms26157526
Int J Mol Sci. 2025 Jul 28;26(15):7305. doi: 10.3390/ijms26157305.
ABSTRACT
The epigenetic landscape plays a pivotal role in regulating the functions of both germ and somatic cells (Sertoli and Leydig cells) within the testis, which are essential for male fertility. While somatic cells support germ cell maturation and testosterone synthesis, the epigenetic regulation of germ cells is critical for proper spermatogenesis and function. Epigenetic modifications such as DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs (ncRNAs) are crucial for regulating gene expression that is essential for spermatogenesis and reproductive function. Although numerous studies have highlighted the significance of the epigenome and its implications for male reproductive health, a comprehensive overview of the existing literature and knowledge is lacking. This review aims to provide an in-depth analysis of the role of epigenetics in spermatogenesis and reproductive health, with a specific focus on DNA methylation, histone remodeling, and small noncoding RNAs (sncRNAs). Additionally, we examine the impact of lifestyle and environmental factors, such as diet, smoking, physical activity, and exposure to endocrine-disrupting chemicals, on the sperm epigenome. We emphasize how these factors influence fertility, embryonic development, and potential transgenerational inheritance. This review underscores how recent advances in the understanding of the epigenetic modulation of testicular function can inform the pathophysiology of male infertility, thereby paving the way for the development of targeted diagnostic and therapeutic strategies.
PMID:40806437 | PMC:PMC12347184 | DOI:10.3390/ijms26157305
Foods. 2025 Jul 30;14(15):2689. doi: 10.3390/foods14152689.
ABSTRACT
PET (polyethylene terephthalate) bottles contain different chemicals that can act as endocrine disruptors. Phthalates and bisphenol A can be found in various foods and beverages packaged in PET packaging or aluminum cans. For some phthalates, the European Union has established specified tolerable daily intakes for humans. This study aimed to establish the changes, types of phthalates (dimethyl phthalate, diethyl phthalate, diisobutyl phthalate, dibutyl phthalate, bis(2-ethylhexyl) phthalate, di-n-octyl phthalate), and bisphenol A concentrations in beer packaged in PET bottles and stored at two temperatures (4 °C and 20 °C) for four months. Beers were obtained from a local brewery after packaging into PET bottles and stored at the designated temperatures. GC-MS analysis was performed to determine phthalates and bisphenol A. Obtained data show that beers packaged in PET bottles can contain significant amounts of bisphenol A, and that their concentration increases with storage time. Phthalates were also identified in the samples, with the highest concentration of bis(2-ethylhexyl) phthalate found in the sample kept at 20 °C after 1 month of storage, sample P5; this concentration was 164.814 µg/L. BPA was recorded with the highest concentration in sample P11, which underwent 4 months of storage at a temperature of 20 °C.
PMID:40807627 | PMC:PMC12346225 | DOI:10.3390/foods14152689
Int J Mol Sci. 2025 Aug 6;26(15):7600. doi: 10.3390/ijms26157600.
ABSTRACT
Globally, endometriosis affects almost 10% of reproductive-aged women, leading to chronic pain and discomfort. Endocrine-disrupting compounds (EDCs) seem to play a pivotal role as a causal factor. The current manuscript aims to explain potential molecular pathways, synthesize current evidence regarding EDCs as causative agents of endometriosis, and highlight implications in the general population and clinical work. A thorough review of experimental, epidemiologic, and mechanistic research studies was conducted to explain the association between EDCs and endometriosis. Among the primary EDCs under investigation are polychlorinated biphenyls, dioxins, phthalates, and bisphenol A (BPA). Despite methodological heterogeneity and some discrepancies, epidemiologic evidence supports a positive association between some increased levels of BPA, phthalates, and dioxins in urine or in blood, and endometriosis. Experiments support some effect of EDCs on endometrial cells and causing endometriosis. EDCs function as xenoestrogens, alter immune function, induce oxidative stress, and disrupt progesterone signaling. Epigenetic reprogramming may play a role in mediating EDC-induced endometriosis. Endocrine, immunological, and epigenetic pathways link EDCs and endometriosis. Prevention techniques require deeper comprehension of those factors. Causal linkages and possible treatment targets should be based on longitudinal studies and multi-omics techniques. Restriction of EDCs could be beneficial for endometriosis prevalence limitation.
PMID:40806727 | PMC:PMC12347297 | DOI:10.3390/ijms26157600
Ecotoxicol Environ Saf. 2025 Aug 13;303:118831. doi: 10.1016/j.ecoenv.2025.118831. Online ahead of print.
ABSTRACT
Bisphenol S (BPS), a widespread plasticizer and endocrine-disrupting compound, can adversely affect steroidogenesis and the hypothalamic-pituitary-gonadal (HPG) axis. This study exposed adult male zebrafish (Danio rerio) to an environmentally relevant BPS concentration (0.5 µg/L) for 14 days (d), assessing its effects on 11-ketotestosterone (11-KT) levels, spermatogenesis, and sperm quality. Additionally, we examined paternal transmission of BPS effects by breeding exposed males with untreated females and evaluating hatching rates, development, survival, and gene expression in offspring. Direct embryonic exposure (0.5 µg/L) was also investigated. BPS exposure increased 11-KT levels in plasma and testes, stimulated meiotic and post-meiotic cysts, and enhanced sperm production. These histomorphometric changes aligned with upregulated expression of sycp3l (meiotic marker), cyp17a1 (androgen synthesis), and genes regulating epigenetic modifications. However, sperm quality was impaired, with reduced motility and fertilization success. In the F1 generation, paternal BPS exposure led to delayed hatching, increased malformations (e.g., absent somites, tail detachment), and higher mortality. In contrast, direct embryonic exposure did not significantly impact development or survival but elevated estrogenic gene expression (esr1, cyp19a1b, vtg1). No estrogenic effects were observed in exposed adults or F1 larvae. Our findings uniquely demonstrate that paternal BPS exposure has greater adverse effects on embryo development and survival than direct embryonic exposure. This study highlights the impact of BPS on hormonal regulation, spermatogenesis, sperm quality, and transgenerational viability, providing new insights into its ecological risks.
PMID:40812092 | DOI:10.1016/j.ecoenv.2025.118831
Aquat Toxicol. 2025 Aug 11;287:107538. doi: 10.1016/j.aquatox.2025.107538. Online ahead of print.
ABSTRACT
Bisphenol A (BPA), a pervasive environmental endocrine disruptor, increasingly threatens aquatic ecosystems due to its reproductive toxicity. This study investigates how BPA disrupts ovarian development in Macrobrachium nipponense - by analyzing its tissue-specific bioaccumulation (ovaries, hepatopancreas, fertilized eggs), antioxidant responses, and developmental gene regulation. Experimental results demonstrated that after 10-day exposure to 10, 100, and 1000 μg/L BPA, significant BPA accumulation was observed in both ovaries and hepatopancreas, while fertilized eggs showed notable accumulation only at the highest concentration (1000 μg/L) (P < 0.05). The ovarian glutathione peroxidase (GSH-Px) activity displayed a concentration-dependent increase, contrasting with the inverse pattern observed in fertilized eggs. Gene expression analysis revealed that cytochrome P450 49A1 (CYP49a1) in both ovaries and hepatopancreas reached peak levels at the highest BPA concentration, whereas cathepsin D (CTSD) and catalase (CAT) expression peaked at the intermediate concentration (100 μg/L) in both tissues (P < 0.05), while female sterile homeotic (fsh) in ovaries remained steady but significantly decreased in hepatopancreas upon BPA exposure (P < 0.05). These results provide preliminary evidence that BPA may disrupt ovarian development in M. nipponense through interfering with antioxidant systems and altering the expression of key developmental genes, highlighting its potential endocrine-disrupting effects in this commercially important crustacean species.
PMID:40812141 | DOI:10.1016/j.aquatox.2025.107538
Environ Res. 2025 Aug 12;285(Pt 4):122583. doi: 10.1016/j.envres.2025.122583. Online ahead of print.
ABSTRACT
BACKGROUND: Phthalates, a group of endocrine disrupting chemicals used in plastics, are ubiquitous in the environment and may influence cellular processes related to child health and development. Mitochondrial DNA copy number (mtDNAcn), telomere length (TL), and DNA methylation-based epigenetic gestational age acceleration (EGAA) are accessible biomarkers associated with biological aging and development. Little is known about how gestational phthalate exposure, individually and in mixtures, may impact biomarkers of biological aging through childhood.
METHODS: We used data and samples from the Columbia Children's Center for Environmental Health (CCCEH) Mothers and Newborns Cohort, which recruited women in the third trimester from Northern Manhattan and the South Bronx, New York. Children returned for follow up at ages 5 and 7. We measured phthalate metabolites in third trimester maternal urine, relative mtDNAcn in cord blood (n = 262) or childhood whole blood (n = 340), relative leukocyte TL (rLTL) in cord blood (n = 151) or childhood whole blood (n = 155), and cord blood DNA methylation (n = 188). Phthalates were assessed as metabolites or summed into parent compounds. Associations between phthalate exposure and biomarkers of aging were modeled with generalized linear models. Phthalate mixture effects were assessed using quantile g-computation.
RESULTS: Associations between phthalate metabolites and mtDNAcn and rLTL may reflect altered cellular health but were not robust to multiple comparison correction. At birth, a 10 % increase in monobutyl phthalate was positively associated with mtDNAcn (β = 1.96, 95 % CI: 0.40, 3.52) while a 10 % increase in mono-iso-butyl phthalate was negatively associated with mtDNAcn (β = -1.51, 95 % CI: -2.90, -0.12). A 10 % increase in mono-(3-carboxypropyl) phthalate was associated with a 1.06 percent increase in rLTL at birth (β = 1.06, 95 % CI: 0.17, 1.95). No significant associations were seen with phthalate exposure and EGAA, nor the phthalate mixture.
CONCLUSION: We observed low evidence for the impact of phthalate metabolites on biomarkers of aging.
PMID:40812703 | DOI:10.1016/j.envres.2025.122583
J Appl Toxicol. 2025 Aug 14. doi: 10.1002/jat.4874. Online ahead of print.
ABSTRACT
Heavy metal exposure (e.g., Pb, Cd, Hg, and As) remains a critical public health concern because of bioaccumulation and links to chronic diseases like hypertension, diabetes, and cancer. This systematic review (PRISMA compliant) synthesizes evidence from 32 studies (2015-2025) elucidating toxicity mechanisms via oxidative stress, inflammation, endocrine disruption, and epigenetic dysregulation. Key biomarkers-blood/urinary metal levels, oxidative stress markers (8-OHdG and MDA), and inflammatory cytokines (CRP, IL-6, and TNF-α)-enable early detection and toxicity assessment. Pro-inflammatory responses dominated across studies, with Pb and Cd consistently elevating CRP, TNF-α, and IL-6, alongside tissue-specific inflammation (liver and kidneys). ELISA emerged as the primary analytical method, although biomarker variability underscored influences of dose, duration, and individual susceptibility. Critically, anti-inflammatory IL-10 was frequently downregulated. We highlight the clinical utility of biomarkers in public health surveillance, chelation therapy, and preventive strategies. Future directions prioritize omics-based profiling, CRISPR technology, portable biosensors, and standardized protocols for real-time monitoring and personalized risk assessment. Integrating current biomarkers with these innovations will advance precision medicine to mitigate heavy metal toxicity globally.
PMID:40813054 | DOI:10.1002/jat.4874
Foods. 2025 Jul 30;14(15):2689. doi: 10.3390/foods14152689.
ABSTRACT
PET (polyethylene terephthalate) bottles contain different chemicals that can act as endocrine disruptors. Phthalates and bisphenol A can be found in various foods and beverages packaged in PET packaging or aluminum cans. For some phthalates, the European Union has established specified tolerable daily intakes for humans. This study aimed to establish the changes, types of phthalates (dimethyl phthalate, diethyl phthalate, diisobutyl phthalate, dibutyl phthalate, bis(2-ethylhexyl) phthalate, di-n-octyl phthalate), and bisphenol A concentrations in beer packaged in PET bottles and stored at two temperatures (4 °C and 20 °C) for four months. Beers were obtained from a local brewery after packaging into PET bottles and stored at the designated temperatures. GC-MS analysis was performed to determine phthalates and bisphenol A. Obtained data show that beers packaged in PET bottles can contain significant amounts of bisphenol A, and that their concentration increases with storage time. Phthalates were also identified in the samples, with the highest concentration of bis(2-ethylhexyl) phthalate found in the sample kept at 20 °C after 1 month of storage, sample P5; this concentration was 164.814 µg/L. BPA was recorded with the highest concentration in sample P11, which underwent 4 months of storage at a temperature of 20 °C.
PMID:40807627 | PMC:PMC12346225 | DOI:10.3390/foods14152689
Cell Commun Signal. 2025 Aug 14;23(1):372. doi: 10.1186/s12964-025-02371-0.
ABSTRACT
BACKGROUND: In many species, including human, stress is accompanied by disruption of reproductive functions. The endocrine stress-response is activated and regulated by members of the corticotropin releasing factor (CRF) protein family. Stress stimuli may affect reproductive functions locally, recruiting autocrine/paracrine strategies. Yet, the molecular mechanisms mediating these effects are not fully understood.
METHODS: To explore the molecular mechanism mediating the ovarian stress response, we used three different models: (1) ICR mice subjected to chronic variable stress (CVS) procedure for 4 weeks. The stress procedure consisted of 9 different stressors per week, approximately 2 stressors per day both in the dark and the light phases. (2) wild-type mice undergoing intraovarian injection of the CRF receptor antagonist, β-asstressin, and (3) CRF-R1 knockout mice.
RESULTS: We report herein that ovulation rate was significantly elevated, and the litter size was substantially increased, in the following estrous cycle of female mice subjected to mild chronic variable stress (CVS). These females exhibited lower serum estrogen levels associated with reduced ovarian 17β-HSD3 expression. Exploration of the involvement of a neuroregulatory mechanism in this event revealed upregulation of the corticotropin releasing factor type 1 receptor (CRFR1) in the theca-interstitial cells of large ovarian follicles. In agreement, CRFR1 knockout mice, as well as wild-type females undergoing intraovarian injection of the CRF receptor antagonist, β-asstressin, displayed reduced ovulation rate, enhanced estrogen secretion and an increase in 17β-HSD3 expression.
CONCLUSIONS: Our findings show a direct gonadal response to neuroendocrine and central stress-response regulators. The mechanism of this unexpected beneficial effect of CVS on reproduction may provide a neuro-endocrine background to the well-known "Baby Boom" phenomenon.
PMID:40813666 | PMC:PMC12351781 | DOI:10.1186/s12964-025-02371-0
Biol Methods Protoc. 2025 Jul 1;10(1):bpaf052. doi: 10.1093/biomethods/bpaf052. eCollection 2025.
ABSTRACT
Obesity is defined as a disease in which abnormal excessive body fat accumulation causes adverse effects on health. One proposed contributing factor to the rise in obesity is the exposure to endocrine disruptors acting as obesogens. Semitransparent zebrafish larvae, with their well-developed white adipose tissue (WAT), offer a unique opportunity for studying the effects of toxicant chemicals and pharmaceuticals on adipocyte dynamics and whole-organism adiposity in a vertebrate model. The work presented here is a detailed optimized zebrafish obesogenic test (ZOT) protocol. The method allows to assess the effects of diet composition, drugs and environmental contaminants, acting as obesogens or anti-obesogens, alone or in combination, on WAT levels in zebrafish larvae. Zootechnical parameter guidelines, including larvae rearing conditions, feeding, and selection of larvae to be enrolled are provided. An optimized procedure for in vivo staining of adipocyte lipid droplets with Nile Red before and after exposure to compounds is provided to enhance reproducibility. Using suitable subcutaneous WAT locations, a rationally defined guide for wide-field fluorescence microscopy signal acquisition is proposed. The ZOT analysis software was developed to enable automated and efficient image data processing by using custom-trained supervised deep-learning models. The present ZOT protocol distinguishes intrinsic variability of the test method from the biological effect measured. It is the basis of a specific, sensitive, and robust quantitative in vivo assay for high-throughput screening of compounds and food content that influence adipocyte hyper/hypotrophy. As such, it provides relevant information for environmental as well as human risk and benefit assessments.
PMID:40799311 | PMC:PMC12343004 | DOI:10.1093/biomethods/bpaf052
Transl Androl Urol. 2025 Jul 30;14(7):2118-2123. doi: 10.21037/tau-2025-319. Epub 2025 Jul 25.
ABSTRACT
BACKGROUND: Chronic kidney disease (CKD) and its advanced form, end-stage kidney disease (ESKD), disrupt male reproductive capacity, largely due to endocrine disturbances and impaired sperm production. Kidney transplantation (KTx) may reverse these effects by normalizing kidney function and recalibrating the hypothalamic-pituitary-gonadal (HPG) axis. Here, we report the first known case of natural conception in a male with ESKD and non-obstructive azoospermia (NOA) after KTx.
CASE DESCRIPTION: A 32-year-old man experienced reduced sexual desire, mild erectile dysfunction, and infertility for four years. Workup revealed stage 3 CKD from chronic glomerulonephritis and hypertension, later advancing to ESKD, along with NOA confirmed by two semen analyses. Choosing KTx over prompt surgical sperm extraction, he achieved normalized renal function and partial endocrine recovery by 3 months post-transplant. Semen analysis confirmed restored sperm production, leading to a spontaneous pregnancy, which unfortunately ended in a miscarriage at 7 weeks.
CONCLUSIONS: This case underscores the possibility of fertility restoration in azoospermic men with ESKD after KTx. Despite challenges such as sperm quality issues and immunosuppressive drugs potentially affecting outcomes, KTx appears to enhance sexual function and sperm production, providing a promising fertility option for ESKD patients. Additional reports are essential to elucidate treatment strategies and the long-term impacts of immunosuppressive agents on male reproductive health.
PMID:40800101 | PMC:PMC12336720 | DOI:10.21037/tau-2025-319
Ecotoxicol Environ Saf. 2025 Aug 12;303:118845. doi: 10.1016/j.ecoenv.2025.118845. Online ahead of print.
ABSTRACT
OBJECTIVE: To provide a theoretical basis for investigating ADHD etiology in children, we aimed to investigate an association between environmental endocrine disruptors (EEDs) and attention deficit and hyperactivity disorder (ADHD) in children.
METHODS: Relevant studies on the relationship between EEDs and ADHD in children from January 2008 to December 2023 were collected. The fixed-effects model was used for studies with I2 < 50 %, whereas the random-effects model was used for studies with I2 > 50 % per the results of the literature heterogeneity test. A sensitivity analysis was performed to evaluate the stability of the combined results. Furthermore, Egger's and Begg's tests were used in combination with funnel plots to evaluate publication bias.
RESULTS: In total, 19 articles were included in the present meta-analysis. These results indicated that BPA and PAE exposure would increase the risk of ADHD. The results of the meta-analysis of sex subgroups showed that exposure to BPA, PAEs, PAHs increased the risk of ADHD in male children, whereas an inverse association was observed between exposure to PFAS and ADHD in female children.
CONCLUSION: EEDs included in this study, such as BPA and PAEs, were associated with the increased risk of ADHD in children.
PMID:40803269 | DOI:10.1016/j.ecoenv.2025.118845
Ecotoxicol Environ Saf. 2025 Aug 12;303:118845. doi: 10.1016/j.ecoenv.2025.118845. Online ahead of print.
ABSTRACT
OBJECTIVE: To provide a theoretical basis for investigating ADHD etiology in children, we aimed to investigate an association between environmental endocrine disruptors (EEDs) and attention deficit and hyperactivity disorder (ADHD) in children.
METHODS: Relevant studies on the relationship between EEDs and ADHD in children from January 2008 to December 2023 were collected. The fixed-effects model was used for studies with I2 < 50 %, whereas the random-effects model was used for studies with I2 > 50 % per the results of the literature heterogeneity test. A sensitivity analysis was performed to evaluate the stability of the combined results. Furthermore, Egger's and Begg's tests were used in combination with funnel plots to evaluate publication bias.
RESULTS: In total, 19 articles were included in the present meta-analysis. These results indicated that BPA and PAE exposure would increase the risk of ADHD. The results of the meta-analysis of sex subgroups showed that exposure to BPA, PAEs, PAHs increased the risk of ADHD in male children, whereas an inverse association was observed between exposure to PFAS and ADHD in female children.
CONCLUSION: EEDs included in this study, such as BPA and PAEs, were associated with the increased risk of ADHD in children.
PMID:40803269 | DOI:10.1016/j.ecoenv.2025.118845
Front Public Health. 2025 Jul 28;13:1621495. doi: 10.3389/fpubh.2025.1621495. eCollection 2025.
ABSTRACT
BACKGROUND: Perfluorooctanoic acid (PFOA) and Perfluorooctane sulfonate (PFOS) are among numerous chemicals in the Per- and polyfluoroalkylated substances (PFAS) group, which are commonly present in various consumer and industrial products. These chemicals are recognized for their persistency, the ability to accumulate in biological systems and their documented adverse effects on human health. Previous research, which has primarily centered on global methylation patterns, has suggested that some effects of PFAS on human health may be linked to modifications in DNA methylation (DNAm). The aim of our study was to assess the relationship between the serum levels of PFOS and PFOA and CpG site-specific methylation of DNA from peripheral blood.
METHODS: We used a case-control study on breast cancer nested within the E3N cohort, a prospective study of French women, in which we measured DNAm at more than 850,000 CpG sites with the Illumina Infinium MethylationEPIC BeadChip for 166 case-control pairs. Serum levels of PFOS and PFOA were measured by liquid chromatography coupled to tandem mass spectrometry.
RESULTS: We found 64 CpG sites with significant hypomethylation or hypermethylation associated with increased levels of PFOA or PFOS (p-valueBonferroni < 0.05). The strongest association was found between PFOA serum levels and decreased DNAm at cg06874740 (p-valueBonferroni = 2.2×10-5) and between PFOS serum levels and decreased DNAm at cg02793158 (p-valueBonferroni = 9.3×10-5). Gene-set enrichment analyses using all CpG sites associated with PFOA or PFOS with an unadjusted p-value <0.01, identified 20 KEGG pathways for each of these compounds.
CONCLUSION: PFAS exposure may be linked to substantial and widespread changes in the methylome that may be involved in the consequences on health of these pollutants. Our findings indicate that the biological and health effects of PFOA and PFOS may be more intricate and varied than previously thought, reinforcing the need for policies aimed at regulating this class of endocrine-disrupting chemicals.
PMID:40791616 | PMC:PMC12336190 | DOI:10.3389/fpubh.2025.1621495
J Clin Res Pediatr Endocrinol. 2025 Aug 12. doi: 10.4274/jcrpe.galenos.2025.2025-3-22. Online ahead of print.
ABSTRACT
OBJECTIVE: Endocrine-disrupting chemicals (EDC) may influence the process of puberty including the development of premature thelarche (PT). This study aimed to investigate the relation between exposure to bisphenol A (BPA) and parabens with PT among a sample of Iranian girls.
METHODS: This case-control study was conducted in 2022-2023 on girls with a mean (SD) age of 7.5(0.6) years in Isfahan, Iran. Participants were 90 newly diagnosed PT cases and 114 healthy controls. Spot urine samples were collected from both groups to measure the levels of BPA and paraben metabolites. We performed analyses of BPA and paraben metabolites including methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP) and benzylparaben (BzP) using gas chromatography-mass spectrometry. The association between concentrations of creatinine-standardized urinary bisphenol A and parabens and PT was analyzed with multiple logistic regression models, after adjusting for potential confounders.
RESULTS: The results showed that individuals in the highest quartile of methyl paraben (OR=4.3, 95% CI:1.2-14.9, P=0.023), ethyl paraben (OR=4.7, 95% CI:1.3-17.2, P=0.018) and BPA (OR=5.03, 95% CI:1.4-17.9, P=0.013) had a significantly higher odds for PT compared to those in the lowest quartile.
CONCLUSION: The findings of this study suggest that exposure to BPA, MeP and EtP is related to increased odds of early breast development in girls. Limiting the exposure to these chemicals may help to reduce the risk of precocious puberty.
PMID:40793795 | DOI:10.4274/jcrpe.galenos.2025.2025-3-22
Environ Geochem Health. 2025 Aug 12;47(9):371. doi: 10.1007/s10653-025-02707-2.
ABSTRACT
Di-butyl phthalates are endocrine disruptors commonly used in plastics to increase the flexibility and durability of polymeric materials. Due to their extensive use in personal care products and plastic packaging, and their tendency to leach from these materials, di-butyl phthalates have been frequently detected in various aquatic environments, including groundwater, drinking water, and wastewater. Given their frequent occurrences in water sources, di-butyl phthalates are capable of interfering with the endocrine system, which may lead to cancer, reproductive problems, and impaired physical growth. Finding energy-efficient and affordable technology to remove di-butyl phthalates from the atmosphere and the aquatic system is imperative considering all these ramifications. With emphasis on pilot-scale and commercial applications, this review assesses existing microbiological and advanced di-butyl phthalates treatment methods, degradation mechanisms such as photocatalysis, knowledge gaps, and future research prospects. Among various remediation strategies, biological treatment methods stand out for their high efficiency in degrading di-butyl phthalates, often exceeding 90%. Despite these promising results, future research should focus on developing environmentally friendly and time-efficient techniques for di-butyl phthalates removal.
PMID:40794312 | DOI:10.1007/s10653-025-02707-2
Biol Futur. 2025 Aug 12. doi: 10.1007/s42977-025-00282-2. Online ahead of print.
ABSTRACT
The fauna of Lake Hévíz is unique due to its status as the world's only natural warm-water medicinal lake with a peat bed. A population of dwarf common carp (Cyprinus carpio carpio morpha hungaricus) forms an isolated, self-sustaining community in the lake, adapted to extreme thermal and chemical conditions. During continuous research conducted since 2007, we identified a hermaphroditic individual for the first-time following sampling during the winter period in 2024. Macroscopic examination revealed testicular tissue distinguishable from ovarian tissue. Histological analysis indicated that the small-bodied fish were in a pre-spawning phase, with gonads displaying traits of simultaneous hermaphroditism. In addition was capable of producing mature eggs and sperm concurrently. According to both literature and our experimental findings, this individual may have been capable of self-fertilization. Further investigation is required to ascertain whether specific or combined suboptimal environmental factors and/or endocrine-disrupting chemicals contributed to the emergence of hermaphroditism in this individual.
PMID:40794361 | DOI:10.1007/s42977-025-00282-2
Spectrochim Acta A Mol Biomol Spectrosc. 2025 Aug 7;345:126799. doi: 10.1016/j.saa.2025.126799. Online ahead of print.
ABSTRACT
Initially, it was considered as a feasible solution to replace the harmful bisphenol A with structurally similar bisphenol S (BPS). However, with the deepening of research, BPS has also been pointed out to have similar endocrine-disrupting effects and physiological hazards to bisphenol A. Therefore, it is necessary to develop an efficient and convenient method for BPS detection. By combining pH adjustment and the polydopamine nanoparticles (DPA-PDs), which were synthesized according to a one-step hydrothermal method with dopamine hydrochloride as the precursor, a ratiometric fluorescence sensing platform for BPS has been constructed in this work. The analyte BPS has weak fluorescence in acidic and neutral environments. However, deprotonated BPS exhibits stronger fluorescence emission at 460 nm in an alkaline environment, and the synchronously enhanced absorption bands of BPS overlaps with both the excitation spectrum and emission spectrum of DPA-PDs. Consequently, the fluorescence of DPA-PDs can be quenched by BPS based on the inner filtration effect, and the intrinsic fluorescence of BPS is positively correlated with the concentration of BPS. The limit of detection for the single-signal sensing model based on the intrinsic fluorescence of BPS is as low as 0.075 μM, and the limit of detection for the ratiometric fluorescence sensing model based on the enhanced BPS versus quenched DPA-PDs is 0.257 μM. The proposed method does not require composite materials with complex preparation processes, and the advantages of sensitivity, rapidity and simplicity are conducive to the application in BPS monitoring.
PMID:40795716 | DOI:10.1016/j.saa.2025.126799
J Sex Med. 2025 Aug 10:qdaf205. doi: 10.1093/jsxmed/qdaf205. Online ahead of print.
ABSTRACT
BACKGROUND: Phthalates are endocrine-disrupting chemicals that can dysregulate hormonal systems supporting female sexual function (eg, estrogen interference). Female sexual function is important for positive sexual expression, fertility, and well-being but remains understudied in the context of environmental toxicants to which females are ubiquitously exposed. Identifying environmental determinants of female sexual dysfunction can inform exposure-reduction strategies and clinical practice to improve sexual health.
AIM: We investigated associations between phthalate exposure and sexual function in a cohort of North American females.
METHODS: We leveraged cross-sectional data from a subset of 21-45-year-old females trying to conceive enrolled in Pregnancy Study Online (n = 347) to assess associations between phthalate and phthalate alternative exposure and sexual function, measured on a modified version of the Female Sexual Function Index-6 (FSFI-6). We summed FSFI-6 responses (range = 2-30); lower scores reflected poorer function. We measured urinary concentrations of 18 phthalate and alternative metabolites using online solid phase extraction coupled with high-performance liquid chromatography isotope dilution tandem mass spectrometry. Given that the biomarkers were nonlinearly associated with FSFI-6 scores, we categorized creatinine-corrected biomarker concentrations in tertiles. We used multivariable linear regression to estimate mean differences (β) with 95% confidence intervals (CIs) in FSFI-6 scores per tertile increase in biomarker concentrations, adjusting for hypothesized confounders. In secondary analyses, we considered individual FSFI-6 items (range = 1-5) as outcome variables.
OUTCOMES: Female sexual function measured on the FSFI-6.
RESULTS: Most biomarkers were not associated with FSFI-6 scores. Mono-n-butyl phthalate concentrations were weakly and non-monotonically associated with lower summed FSFI-6 scores (β = -0.8, 95% CI = -1.8, 0.2) and orgasm scores (β = -0.3, 95% CI = -0.7, 0.1) at the second (vs first) tertile, reflecting poorer sexual function. Mono-2-ethyl-5-carboxypentyl terephthalate concentrations were weakly associated with poorer scores for orgasm, while other biomarkers (notably, mono-carboxyisononyl phthalate) were associated with higher summed FSFI-6 and FSFI-6 item scores.
CLINICAL IMPLICATIONS: Exposure to phthalates should be considered in clinical settings, particularly for females experiencing issues with sexual function.
STRENGTHS AND LIMITATIONS: This study represents one of the first to assess associations of phthalate exposure and female sexual function, and we investigated associations in an established cohort with a validated measure of sexual function. We were limited by our sample size and cross-sectional study design.
CONCLUSION: Although associations for most phthalate biomarkers were null, some were weakly associated with female sexual function, suggesting exposure to certain chemicals may affect female sexual function with implications for clinical practice and exposure reduction strategies.
PMID:40795774 | DOI:10.1093/jsxmed/qdaf205
Annu Rev Pharmacol Toxicol. 2025 Aug 12. doi: 10.1146/annurev-pharmtox-071724-100915. Online ahead of print.
ABSTRACT
When I was young and pictured my future, it wasn't a path that could be determined a priori. The world was full of interesting things. Obtaining the qualifications to become a professor and a researcher was the easy part. The rest relied on being in the right place at the right moment and having the intuition to feel the importance of events we were witnessing. This is how I met my mentors and how my scientific partner and I came upon the paradox that caused us to propose the principle of biological inertia. This is also how we discovered that estrogens leached from plasticware were ruining our experiments, and thus we became "toxicologists by accident." Indeed, we were never formally trained in pharmacology or toxicology; however, our discovery that the estrogen nonylphenol leached from plastics made us pioneers of the new field of endocrine disruptors that encompasses endocrinology and toxicology.
PMID:40796130 | DOI:10.1146/annurev-pharmtox-071724-100915
Front Public Health. 2025 Jul 28;13:1621495. doi: 10.3389/fpubh.2025.1621495. eCollection 2025.
ABSTRACT
BACKGROUND: Perfluorooctanoic acid (PFOA) and Perfluorooctane sulfonate (PFOS) are among numerous chemicals in the Per- and polyfluoroalkylated substances (PFAS) group, which are commonly present in various consumer and industrial products. These chemicals are recognized for their persistency, the ability to accumulate in biological systems and their documented adverse effects on human health. Previous research, which has primarily centered on global methylation patterns, has suggested that some effects of PFAS on human health may be linked to modifications in DNA methylation (DNAm). The aim of our study was to assess the relationship between the serum levels of PFOS and PFOA and CpG site-specific methylation of DNA from peripheral blood.
METHODS: We used a case-control study on breast cancer nested within the E3N cohort, a prospective study of French women, in which we measured DNAm at more than 850,000 CpG sites with the Illumina Infinium MethylationEPIC BeadChip for 166 case-control pairs. Serum levels of PFOS and PFOA were measured by liquid chromatography coupled to tandem mass spectrometry.
RESULTS: We found 64 CpG sites with significant hypomethylation or hypermethylation associated with increased levels of PFOA or PFOS (p-valueBonferroni < 0.05). The strongest association was found between PFOA serum levels and decreased DNAm at cg06874740 (p-valueBonferroni = 2.2×10-5) and between PFOS serum levels and decreased DNAm at cg02793158 (p-valueBonferroni = 9.3×10-5). Gene-set enrichment analyses using all CpG sites associated with PFOA or PFOS with an unadjusted p-value <0.01, identified 20 KEGG pathways for each of these compounds.
CONCLUSION: PFAS exposure may be linked to substantial and widespread changes in the methylome that may be involved in the consequences on health of these pollutants. Our findings indicate that the biological and health effects of PFOA and PFOS may be more intricate and varied than previously thought, reinforcing the need for policies aimed at regulating this class of endocrine-disrupting chemicals.
PMID:40791616 | PMC:PMC12336190 | DOI:10.3389/fpubh.2025.1621495
Plant Direct. 2025 Aug 7;9(8):e70095. doi: 10.1002/pld3.70095. eCollection 2025 Aug.
ABSTRACT
Houttuynia cordata is an important medicinal and vegetable crop in Southwest China. Due to the accumulation of heavy metal ions such as lead ions (Pb2+) in H. cordata, consumption of this plant carries risks, such as ingestion of lead-contaminated H. cordata, may lead to Pb2+ bioaccumulation, which is associated with developmental retardation, endocrine disruption, and impairments to immune and neurological functions. In order to screen H. cordata germplasm for low Pb2+ absorption and identify the Pb2+ adsorption-related agronomic traits and molecular markers, the genetic diversity of a germplasm resource of H. cordata comprising collected 72 accessions was comprehensively evaluated based on agronomic traits and Pb2+ contents in the underground stems of the plant. Further, intersimple sequence repeats (ISSR) markers and generalized linear model (GLM) correlation analyses were performed to identify the ISSR loci related to the Pb2+ absorption. Ward clustering analysis grouped the 72 accessions of H. cordata into five major classes through analysis of morphological traits. Combined analysis of the Pb2+ contents of underground stems with the phenotypic traits revealed significant changes in members within the five classes, indicating that the Pb2+ content significantly affected the results of the evaluation of agronomic traits. Greyscale analysis and subsequent verification revealed that the underground stem thickness was closely related to the Pb2+ absorption. Based on ISSR markers and subsequent verification, two loci, namely, Locus 21 and Locus 29, were found to have better screening effects on germplasms with low Pb2+ adsorption. The accessions that did not carry these two loci in the genome generally exhibited low lead ion adsorption. This study presents a faster marker-based screening for H. cordata plants that are safer for consumption.
PMID:40786686 | PMC:PMC12331442 | DOI:10.1002/pld3.70095
Environ Sci Technol. 2025 Aug 19;59(32):16839-16851. doi: 10.1021/acs.est.4c14630. Epub 2025 Aug 10.
ABSTRACT
As an alternative to traditional pesticides, sulfoxaflor (SFX) is a sulfoximine insecticide with the same mechanism of action as neonicotinoid insecticides (NNIs). However, increasing evidence suggests that SFX poses a threat to aquatic organisms. To investigate the toxic effects and potential risks in amphibians, bioaccumulation and elimination experiments were conducted at environmentally relevant concentrations. The results indicate that although SFX exhibits low acute toxicity and accumulation, it demonstrates neurotoxicity and endocrine-disruptive properties. SFX alters regulatory patterns of growth-related genes and interferes with the regulation of thyroid hormones and its genes, promoting the tadpoles' growth. Additionally, SFX induces oxidative stress, leading to inflammation and immune regulation in the tadpoles. It also affects neurotransmitter transmission as well as the genes associated with neural synapses, receptor, and signal transmission and interferes with tadpole behavior. These toxic effects persisted until the elimination stage. Compared with other NNIs, SFX has the most binding sites with AChR and a weak interaction, and binding to β-agonists is similar in molecular docking. Risk assessment suggests that SFX has a potential risk and impact on aquatic amphibians, which may be underestimated. The result provides valuable reference and new perspective for the ecological safety assessment and supervision of SFX, NNIs, and insecticides of low acute toxicity.
PMID:40785081 | DOI:10.1021/acs.est.4c14630
Tob Induc Dis. 2025 Aug 8;23. doi: 10.18332/tid/205903. eCollection 2025.
ABSTRACT
INTRODUCTION: Numerous studies have shown that polycyclic aromatic hydrocarbons (PAHs) are endocrine disruptors associated with reproduction, with tobacco smoke identified as a major non-occupational source of PAH exposure. However, there is still a lack of information on the relationship between PAH exposure - particularly from tobacco-related sources - and miscarriage.
METHODS: The data for this study were obtained from the National Health and Nutrition Examination Survey (NHANES) 2005-2014. Excluding populations with missing PAH, miscarriage, or baseline information, a total of 2573 individuals were included in this study. Logistic regression, linear regression, restricted cubic spline (RCS) analysis and subgroup analysis were used to analyze the effects of PAHs.
RESULTS: Following logistic and linear regression analyses, we found that higher concentrations of 2-hydroxynaphthalene, 3-hydroxyfluorene, 2-hydroxyfluorene, 1-hydroxyphenanthrene, and 1-hydroxypyrene were associated with miscarriage (p<0.05, OR>1). Moreover, after RCS, we found a nonlinear relationship between 1-hydroxynaphthalene and miscarriage (p=0.01). The relationship between 1-hydroxynaphthalene and miscarriage could be described as an 'n-shaped' curve, with a cutoff value (4705 ng/L). At concentrations lower than the cutoff, there was a positive correlation between 1-hydroxynaphthalene and miscarriage. Conversely, at concentrations higher than the cutoff, there was a negative correlation between the two variables. Finally, a subgroup analysis was performed to explore the interaction effect of confounders with the outcome variables, to further demonstrate the robustness of the results.
CONCLUSIONS: The probability of miscarriage increases with increasing concentration of certain PAHs in the body. Enhancing monitoring of tobacco-related PAHs exposure is highly important for the prevention of miscarriage.
PMID:40785795 | PMC:PMC12332853 | DOI:10.18332/tid/205903
Probiotics Antimicrob Proteins. 2025 Aug 11. doi: 10.1007/s12602-025-10704-1. Online ahead of print.
ABSTRACT
Chlorpyrifos (CPF), a widely used organophosphorus pesticide, induces adverse effects such as organ toxicity, endocrine disruption, oxidative stress, and histopathological damage in non-target organisms. Emerging evidence suggests that lactic acid bacteria (LABs) can alleviate CPF-induced tissue damage. This study investigated the protective effects of probiotic lactobacilli against subacute CPF toxicity in the heart and lungs of rats. Eight groups of male Sprague‒Dawley rats were exposed to CPF and probiotics for 6 weeks. CPF toxicity triggered lipid peroxidation, evidenced by a 40% and 60% rise in malondialdehyde (MDA) levels in heart and lung tissues, respectively. Additionally, CPF significantly elevated superoxide dismutase (SOD) and IL-1β, indicating oxidative and pro-inflammatory responses. Probiotic treatment effectively suppressed CPF-induced increases in MDA, SOD, and IL-1β. Histopathological analysis demonstrated that Lactobacillus acidophilus (heart) and Lactobacillus casei (lungs), particularly the probiotic bacterial mixture in each respective tissue, attenuated CPF-induced tissue damage. In conclusion, probiotic supplementation mitigates CPF-mediated cardiotoxicity and pulmonary toxicity by modulating antioxidant and inflammatory pathways.
PMID:40788456 | DOI:10.1007/s12602-025-10704-1
Environ Res. 2025 Aug 9;285(Pt 4):122419. doi: 10.1016/j.envres.2025.122419. Online ahead of print.
ABSTRACT
Mixture exposures dominate real-world environmental settings, yet the toxic impacts of neonicotinoid insecticides (NEOs), one of the most widely used pesticide classes, when combined with co-occurring pollutants on non-target invertebrates remain poorly synthesized. This extensive global analysis integrated data from 47 studies retrieved via Web of Science, PubMed, and CNKI, covering 1706 toxicity endpoint records standardized by toxicological parameters (e.g., survival rate, mortality, enzyme activity), pollutant types, exposure conditions, and species taxonomy, and used Hedges'g as the effect size statistic with a three-level model to assess the impact of NEOs and coexisting pollutant mixtures on non-target invertebrate toxicity. The results revealed that the presence of coexisting pollutants changed NEO toxicity, exacerbating growth and development (Hedges' g = -2.61 ± 0.26), accumulation (Hedges' g = 0.98 ± 0.19), and oxidative damage (Hedges' g = -0.59 ± 0.08), while lowering endocrine disruption and neurotoxic effects (Hedges' g = 0.19 ± 0.12) in specific contexts. Variations in toxicity were found to be influenced by the invertebrate species, NEO type, and pollutant category. Specifically, NEO co-toxicity variations affected by co-existing pollutants were recorded in the higher sensitivity of pollinators (e.g., Hymenoptera bees) and aquatic invertebrates, stronger toxicity of thiacloprid/thiamethoxam, amplified NEO toxicity by fungicides, heavy metals, microplastics and inorganic pollutants, the more severe effects of oral compared contact exposure, and the higher vulnerability of juvenile and early life stages. Meta-regression analysis revealed correlations with biological type, pollutant concentrations, types, and exposure durations, with a slight negative correlation observed between NEO levels, exposure time, and impact severity in co-exposure scenarios, as well as no significant associations with logKow. The limitations and prospects of the study highlighted challenges in extrapolating laboratory findings to natural settings, underscoring the need for research focusing on multiple pollutants, prolonged exposure periods, and realistic conditions to enhance ecological risk assessments. This investigation advanced our understanding of combined NEO toxicity mechanisms, providing valuable insights for evidence-based environmental mixture risk management.
PMID:40784634 | DOI:10.1016/j.envres.2025.122419
Sci Total Environ. 2025 Aug 9;997:180214. doi: 10.1016/j.scitotenv.2025.180214. Online ahead of print.
ABSTRACT
Exposure to bisphenols and perfluoroalkyl substances (PFAS) is linked to various health impairments, including (developmental) neurotoxicity. Evidence indicates that bisphenols and PFAS can impact early neurodevelopmental processes such as proliferation, migration, and differentiation, although little is known about the effects of these compounds on neuronal activity and network development. Therefore, we assessed the effects of acute and chronic exposure to different bisphenols (bisphenol-A (BPA), bisphenol-F (BPF), and bisphenol-S (BPS)) and PFAS (perfluorooctanoate (PFOA), perfluorooctanesulfonate (PFOS), and perfluorohexanesulfonate (PFHxS)) on neuronal activity and network development in rat primary cortical cultures using micro-electrode array recordings. Acute exposure to BPA and BPF decreased neuronal activity, while BPS had no effect. Chronic exposure to 100 μM BPA decreased network development, while chronic exposure to 10 μM BPA, 100 μM BPF, and 100 μM BPS induced a hyperexcitation. Thus, differences in the molecular structure of bisphenols and exposure duration influence the effects of these compounds on neuronal activity and network development. In contrast, both acute and chronic exposure to PFOS, PFOA, and PFHxS had limited effects on neuronal activity and network development. Since bisphenols and PFAS are known endocrine-disrupting compounds, we also evaluated the possible involvement of estrogen, glucocorticoid, thyroid hormone, and aryl hydrocarbon receptor pathways in the observed neurotoxic effects. Our cortical cultures appeared insensitive to endocrine-mediated effects of (ant)agonists of these pathways, making it unlikely that the observed neurotoxic effects are endocrine-mediated. These findings contribute to hazard assessment for toxicological risk assessments and emphasize the need to consider molecular structure in evaluating neurotoxicity.
PMID:40784309 | DOI:10.1016/j.scitotenv.2025.180214
Int J Hyg Environ Health. 2025 Aug 9;269:114647. doi: 10.1016/j.ijheh.2025.114647. Online ahead of print.
ABSTRACT
This prospective cohort study investigated the impact of maternal exposure to endocrine-disrupting chemicals, specifically phthalates and bisphenol A (BPA), on infant neurodevelopment. From 2019 to 2022, 672 pregnant women consented to participate in the study during their initial prenatal appointments at the Obstetrics and Gynecology Clinic of King Faisal Specialist Hospital & Research Centre. Two urine samples were collected each trimester to measure seven phthalate metabolites and BPA levels. Neurodevelopmental performance was evaluated using the Ages & Stages Questionnaires® Third Edition at 6, 12, and 18 months of age, and the risk of autism was assessed with the Modified Checklist For Autism in Toddlers at 18 months. Linear mixed models and logistic regression were applied to evaluate trimester-specific and overall associations using natural log-transformed urinary concentrations of phthalates and BPA. Our results showed that each one-unit increase in the log-transformed concentration of specific phthalates and BPA was associated with significant changes in infant developmental scores. During the first trimester, elevated levels of mono-n-butyl phthalate (MnBP), mono-iso-butyl phthalate (MiBP), and BPA were associated with 4.3 %-5.6 % decreases in gross motor (GM) scores. In contrast, monoethyl phthalate (MEP) and low-molecular-weight (∑LMW) phthalates were linked to 4 %-4.5 % increases in communication (COMM) scores. In the third trimester, MECPP and Σ3DEHP were positively associated with GM and fine motor (FM) scores, while MiBP was associated with reduced personal-social (PSoc) scores. Sex-stratified analyses revealed differences in susceptibility, with males showing stronger adverse associations in problem-solving and social domains and females more affected in gross and fine motor scores. Mediation analysis identified free thyroxine (FT4) as a partial mediator, accounting for 12.7 % of the effect of ∑LMW phthalates on COMM scores during the first trimester. However, most mediation effects through maternal thyroid hormones were small and not statistically significant. Additionally, some first-trimester exposures, such as MEP and mono-(2-ethyl-5-oxohexyl) phthalate, appeared to be associated with lower odds of a positive M-CHAT screen. At the same time, MnBP showed a potential increase in risk. However, these exploratory findings were based on crude models and a limited number of positive cases and should be interpreted cautiously. Our study also examined overall exposure to phthalates and BPA across pregnancy, revealing consistent yet subtle impacts across developmental domains. This study adds novel insights by assessing trimester-specific exposures and investigating maternal thyroid hormones as potential mediators of early neurodevelopmental outcomes.
PMID:40784189 | DOI:10.1016/j.ijheh.2025.114647
Sci Total Environ. 2025 Aug 9;997:180214. doi: 10.1016/j.scitotenv.2025.180214. Online ahead of print.
ABSTRACT
Exposure to bisphenols and perfluoroalkyl substances (PFAS) is linked to various health impairments, including (developmental) neurotoxicity. Evidence indicates that bisphenols and PFAS can impact early neurodevelopmental processes such as proliferation, migration, and differentiation, although little is known about the effects of these compounds on neuronal activity and network development. Therefore, we assessed the effects of acute and chronic exposure to different bisphenols (bisphenol-A (BPA), bisphenol-F (BPF), and bisphenol-S (BPS)) and PFAS (perfluorooctanoate (PFOA), perfluorooctanesulfonate (PFOS), and perfluorohexanesulfonate (PFHxS)) on neuronal activity and network development in rat primary cortical cultures using micro-electrode array recordings. Acute exposure to BPA and BPF decreased neuronal activity, while BPS had no effect. Chronic exposure to 100 μM BPA decreased network development, while chronic exposure to 10 μM BPA, 100 μM BPF, and 100 μM BPS induced a hyperexcitation. Thus, differences in the molecular structure of bisphenols and exposure duration influence the effects of these compounds on neuronal activity and network development. In contrast, both acute and chronic exposure to PFOS, PFOA, and PFHxS had limited effects on neuronal activity and network development. Since bisphenols and PFAS are known endocrine-disrupting compounds, we also evaluated the possible involvement of estrogen, glucocorticoid, thyroid hormone, and aryl hydrocarbon receptor pathways in the observed neurotoxic effects. Our cortical cultures appeared insensitive to endocrine-mediated effects of (ant)agonists of these pathways, making it unlikely that the observed neurotoxic effects are endocrine-mediated. These findings contribute to hazard assessment for toxicological risk assessments and emphasize the need to consider molecular structure in evaluating neurotoxicity.
PMID:40784309 | DOI:10.1016/j.scitotenv.2025.180214
Reprod Toxicol. 2025 Aug 9;137:109029. doi: 10.1016/j.reprotox.2025.109029. Online ahead of print.
ABSTRACT
Preeclampsia (PE) is a complex hypertensive disorder and a leading cause of maternal and perinatal morbidity worldwide. Emerging evidence suggests that exposure to endocrine-disrupting chemicals (EDCs) may contribute to the etiology of PE, yet this association remains underexplored. This review aimed to investigate epidemiological and experimental studies assessing the potential link between EDC exposure and PE development. A literature search was conducted across PubMed, ScienceDirect, and Google Scholar for original articles published in the last ten years. Forty studies were selected, including epidemiological cohorts, in vivo, and in vitro models, focusing on the association between EDCs and PE or related biomarkers. Epidemiological findings were heterogeneous: while large cohorts often showed no association, several case-control studies linked specific EDCs, such as bisphenol A, phthalates, cadmium, and PFOS, to increased PE risk and elevated blood pressure. Experimental evidence revealed that EDCs impair key placental processes, including decidualization, angiogenesis, and trophoblast invasion. These disruptions were often accompanied by oxidative stress, hormonal imbalances, and endothelial dysfunction, central features in PE pathogenesis. In vivo models also replicated PE-like syndrome after EDC exposure. Although current epidemiological evidence remains inconsistent, mechanistic studies strongly support the biological plausibility of EDC involvement in PE. This review highlights that the contribution of EDCs to PE may be underestimated and calls for multidisciplinary research to clarify exposure thresholds, vulnerable windows, and population-specific susceptibilities.
PMID:40784377 | DOI:10.1016/j.reprotox.2025.109029
Environ Res. 2025 Aug 9;285(Pt 4):122419. doi: 10.1016/j.envres.2025.122419. Online ahead of print.
ABSTRACT
Mixture exposures dominate real-world environmental settings, yet the toxic impacts of neonicotinoid insecticides (NEOs), one of the most widely used pesticide classes, when combined with co-occurring pollutants on non-target invertebrates remain poorly synthesized. This extensive global analysis integrated data from 47 studies retrieved via Web of Science, PubMed, and CNKI, covering 1706 toxicity endpoint records standardized by toxicological parameters (e.g., survival rate, mortality, enzyme activity), pollutant types, exposure conditions, and species taxonomy, and used Hedges'g as the effect size statistic with a three-level model to assess the impact of NEOs and coexisting pollutant mixtures on non-target invertebrate toxicity. The results revealed that the presence of coexisting pollutants changed NEO toxicity, exacerbating growth and development (Hedges' g = -2.61 ± 0.26), accumulation (Hedges' g = 0.98 ± 0.19), and oxidative damage (Hedges' g = -0.59 ± 0.08), while lowering endocrine disruption and neurotoxic effects (Hedges' g = 0.19 ± 0.12) in specific contexts. Variations in toxicity were found to be influenced by the invertebrate species, NEO type, and pollutant category. Specifically, NEO co-toxicity variations affected by co-existing pollutants were recorded in the higher sensitivity of pollinators (e.g., Hymenoptera bees) and aquatic invertebrates, stronger toxicity of thiacloprid/thiamethoxam, amplified NEO toxicity by fungicides, heavy metals, microplastics and inorganic pollutants, the more severe effects of oral compared contact exposure, and the higher vulnerability of juvenile and early life stages. Meta-regression analysis revealed correlations with biological type, pollutant concentrations, types, and exposure durations, with a slight negative correlation observed between NEO levels, exposure time, and impact severity in co-exposure scenarios, as well as no significant associations with logKow. The limitations and prospects of the study highlighted challenges in extrapolating laboratory findings to natural settings, underscoring the need for research focusing on multiple pollutants, prolonged exposure periods, and realistic conditions to enhance ecological risk assessments. This investigation advanced our understanding of combined NEO toxicity mechanisms, providing valuable insights for evidence-based environmental mixture risk management.
PMID:40784634 | DOI:10.1016/j.envres.2025.122419
Aquat Toxicol. 2025 Aug 6;287:107527. doi: 10.1016/j.aquatox.2025.107527. Online ahead of print.
ABSTRACT
Levonorgestrel (LNG), a common synthetic progestogen, has emerged as an endocrine-disrupting contaminant in aquatic ecosystems. Although recent studies have recognized its androgenic effects, there exist critical gaps in understanding its influence on growth and associated molecular mechanisms. The processes driving anal fin elongation in mosquitofish (Gambusia affinis) following exposure to progestogens, such as LNG, remain poorly characterized. To address these knowledge gaps, we investigated LNG-induced androgenic effects on growth and the molecular basis of anal fin masculinization in adult female mosquitofish exposed to environmentally relevant LNG concentrations (500 ng/L) over a four-week period. Comprehensive physiological and morphological assessments (e.g., Fulton's condition factor, gonadosomatic index, and anal fin/skeletal analyses) revealed significant masculinization in LNG-exposed females. Transcriptomic profiling of anal fin tissue demonstrated that LNG-mediated masculinization and elongation at 500 ng/L were associated with the activation of the transforming growth factor-beta (TGF-β) and bone morphogenetic protein (BMP) signaling pathways. The exposure altered the transcriptional levels of key osteoblast- and osteoclast-related genes (i.e., sp7, col10a1, and nfatc1), implicating dysregulated bone remodeling in fin structural changes. Androgen receptor (ar) expression in anal fin tissue remained unchanged, suggesting that LNG's androgenic effects occurred independently of direct ar transcriptional modulation in this tissue. This study provides the first evidence that LNG disrupts bone morphogenetic and sex-related gene transcription, driving anal fin masculinization in female mosquitofish. These findings advance our understanding of LNG's androgenic impacts and propose the mosquitofish anal fin as a potential biomarker for endocrine disruption. By elucidating molecular pathways linking LNG exposure to morphological changes, this study paves the way for assessing the ecological risks of progestogen pollution in aquatic ecosystems.
PMID:40782708 | DOI:10.1016/j.aquatox.2025.107527
Chem Biodivers. 2025 Aug 8:e01266. doi: 10.1002/cbdv.202501266. Online ahead of print.
ABSTRACT
This study investigated the chemical composition and antioxidant activities of the essential oils and hydrolates from two varieties of spontaneous rosemary: Salvia rosmarinus var. laxiflorus and S. rosmarinus var. troglodytorum, which are endemic to southern Tunisia. Total phenolic and flavonoid contents were quantified, the chemical composition of the essential oils was analyzed by gas chromatography-mass spectrometry (GC-MS), antioxidant activity was determined using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays, and molecular docking along with endocrine-disrupting potential analyses was also performed. The hydrolate of laxiflorus variety had the highest phenolic and flavonoid content. The major compounds identified in essential oils extracted from laxiflorus variety were 1,8-cineole, eugenol, α-pinene, camphor, and α-terpineol, whereas those of troglodytorum variety include 1,8-cineole, camphor, α-pinene, α-terpineol, and borneol. Notably, eugenol was present at a high percentage in the laxiflorus variety, but it was absent in the troglodytorum variety. The essential oils and hydrolates of S. rosmarinus var. laxiflorus exhibited the highest antioxidant activity. Additionally, molecular docking revealed that eugenol had the strongest interaction with the 3QFT protein, whereas 1,8-cineole, camphor, and eugenol showed low endocrine-disrupting potential. Finally, the study demonstrates that rosemary is a natural source of antioxidant compounds and highlights the potential of its essential oils and hydrolates for applications in the pharmaceutical and food industries.
PMID:40779741 | DOI:10.1002/cbdv.202501266
Aquat Toxicol. 2025 Aug 7;287:107521. doi: 10.1016/j.aquatox.2025.107521. Online ahead of print.
ABSTRACT
Environmental pollutants, particularly endocrine disruptors, are known to significantly dysregulate lipid homeostasis, causing severe health issues. However, their obesogenic effects on invertebrate species, such as the planktonic crustacean Daphnia magna, remain poorly understood. Previous research suggested that compounds such as organotin tributyltin and the insecticide pyriproxyfen promote lipid accumulation, particularly triacylglycerol species. However, bulk LC-MS methodologies used did not retain the spatial context of the biomolecules analyzed, failing in providing crucial insights into the tissue-specific molecular effects of pollutant exposure and risk assessment. The present study evaluates the disruptive effects of these compounds at the lipidomic level using a novel spatial MALDI-MSI-based approach integrated with ion mobility. In terms of toxicological assessment, MALDI-MSI revealed distinct lipidomic disruptions. Both pollutants increased glycerolipids, but glycerophospholipids exhibited opposing patterns. Tributyltin significantly altered the lipid composition of the nervous system, whereas pyriproxyfen predominantly affected the cardiovascular system. In conclusion, the integration of MALDI-MSI with ion mobility not only enhanced the identification of lipids but also allowed to provide deeper insights into the tissue-specific toxicological mechanisms of environmental obesogens in Daphnia magna. Additionally, this study emphasizes the potential of these state-of-the-art analytical techniques in advancing spatial biology and environmental risk assessment.
PMID:40779922 | DOI:10.1016/j.aquatox.2025.107521
Environ Int. 2025 Jul 11;202:109681. doi: 10.1016/j.envint.2025.109681. Online ahead of print.
ABSTRACT
BACKGROUND: Population studies have found associations between prenatal exposure to endocrine-disrupting chemicals (EDCs) in personal care products (PCPs) and childhood asthma; however, few have examined adult-onset asthma. We investigated the associations between commonly used PCPs and the risk of adult-onset asthma in a prospective cohort study of U.S. women.
METHODS: We analyzed 39,408 participants from the Sister Study who self-reported their usage frequency of 41 PCPs in the 12-month period before baseline (2003-2009). In our combined PCP analyses, we used Least Absolute Shrinkage and Selection Operator (LASSO) to select key PCPs that predict the risk of adult-onset asthma. In group-specific analyses, PCPs were aggregated into four product groups (i.e., beauty, everyday hair, hygiene, and skincare products). Subsequently, we conducted latent class analysis to identify groups of participants with similar patterns of PCP use (e.g., infrequent (reference), moderate, and frequent). Multivariable Cox regression models were used to assess the associations between PCP use and incident adult-onset asthma.
RESULTS: Over an average 12.5-year follow-up, 1,774 incident asthma cases were identified. We found a positive association between combined PCP use and adult-onset asthma risk (moderate users, hazard ratio [HR] = 1.19 (95% confidence interval (CI):1.05,1.33) and frequent users, HR = 1.19 (95% CI:1.06,1.34)). In group-specific analyses, moderate (HR = 1.21 (95% CI:1.07,1.37)) and frequent (HR = 1.22 (95% CI:1.08,1.38)) users of beauty products had higher asthma risk compared to infrequent users. Similar associations were observed for hygiene (moderate: HR = 1.14 (95% CI:1.01,1.29) and frequent: HR = 1.20 (95% CI:1.06,1.36)) and skincare products (moderate: HR = 1.21 (95% CI:1.06,1.38) and frequent: HR = 1.20 (95% CI:1.06,1.35)).
CONCLUSIONS: Our findings suggest that PCP use potentially contributes to future risk of adult-onset asthma among women.
PMID:40779943 | PMC:PMC12365912 | DOI:10.1016/j.envint.2025.109681
Eur J Med Res. 2025 Aug 8;30(1):725. doi: 10.1186/s40001-025-02910-y.
ABSTRACT
BACKGROUND: Polycystic ovary syndrome (PCOS) and subclinical hypothyroidism (SCH) are both common endocrine disorders. This study investigates the impact of SCH on the endocrine features of patients diagnosed with PCOS.
METHODS: This retrospective study included 124 women diagnosed with PCOS between January 2020 and November 2022. Participants were divided into two groups: those with PCOS alone (n = 93) and those with both PCOS and SCH (n = 31).Clinical parameters (age, body mass index, blood pressure, age at menarche) and endocrine markers were collected. Hormonal measurements included follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), prolactin (PRL), testosterone (TES), progesterone (PRG), TSH, free triiodothyronine (FT3), FT4, and Anti-Müllerian hormone (AMH). Thyroid autoantibodies, including antithyroid peroxidase (TPO-Ab) and antithyroglobulin antibody (TG-Ab), were also assessed. Antral follicle count (AFC) was evaluated using transvaginal ultrasound.
RESULTS: The study found that patients with PCOS and SCH exhibited significantly higher levels of TSH and PRL compared to those with PCOS alone. However, there were no significant differences in PRG, LH, FSH, TES, and E2 levels between the groups. The PCOS group showed a moderate positive correlation between TSH and AMH, whereas the PCOS with SCH group demonstrated a negative correlation between TSH and FSH, albeit not statistically significant.
CONCLUSIONS: Subclinical hypothyroidism in women with PCOS is associated with altered thyroid-prolactin axis activity and a disrupted correlation between TSH and AMH, while gonadotropin levels and ovarian morphology appear unaffected. These findings warrant confirmation through prospective studies.
PMID:40775635 | PMC:PMC12333113 | DOI:10.1186/s40001-025-02910-y
BMC Pregnancy Childbirth. 2025 Aug 8;25(1):830. doi: 10.1186/s12884-025-07980-8.
ABSTRACT
BACKGROUND: Preterm birth (< 37 weeks gestation) is a leading cause of infant morbidity and mortality, yet the underlying causes remain unknown in many cases. Environmental exposures, including endocrine-disrupting chemicals such as phthalates, have been implicated in preterm birth risk. Phthalates are commonly used as plasticisers in consumer products, resulting in widespread human exposure. While some studies suggest an association between maternal phthalate exposure and reduced gestational length, findings remain inconsistent. This study aimed to investigate the relationship between urinary phthalate metabolite concentrations and gestational length in an Australian pregnancy cohort.
METHODS: This prospective cohort study was nested within the Omega-3 to Reduce the Incidence of Prematurity (ORIP) trial. A total of 605 women with singleton pregnancies from South Australia provided urine samples between 22- and 26-weeks' gestation for phthalate metabolite analysis. Thirteen phthalate metabolites were quantified using liquid chromatography-tandem mass spectrometry. Gestational age at birth was determined from medical records. Linear regression models assessed associations between phthalate concentrations and gestational length, adjusting for maternal characteristics including age, BMI, socioeconomic status, education, smoking, and alcohol consumption.
RESULTS: Phthalate metabolites were detected in > 99% of urine samples, with the highest concentrations observed for mono-ethyl phthalate (MEP), mono-isobutyl phthalate (MiBP), and mono-butyl phthalate (MBP). There was no evidence of an association between phthalate exposure and gestational length in either unadjusted or adjusted analyses. No significant association was found between phthalate exposure and preterm birth risk.
CONCLUSIONS: Despite widespread phthalate exposure, no clear link was identified between maternal phthalate levels and shortened gestation in this Australian cohort. However, continued surveillance is needed to monitor emerging plasticiser exposures and inform public health policies on maternal and infant health.
TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry number, ACTRN12613001142729. Date of registration: 27/09/2013.
PMID:40781296 | PMC:PMC12335031 | DOI:10.1186/s12884-025-07980-8
J Hazard Mater. 2025 Aug 5;496:139432. doi: 10.1016/j.jhazmat.2025.139432. Online ahead of print.
ABSTRACT
The rapid expansion of industrial activities has led to the increased release of harmful pollutants into groundwater, posing significant risks to human health and the environment. Traditional toxicity assessments, which rely on animal testing or limited chemical analyses, often fail to capture complex biological effects or efficiently prioritize risks. To address these challenges, we developed an effect-based framework that integrates high-throughput screening (HTS), high-content screening (HCS), Adverse Outcome Pathways (AOPs), and computational ToxPi analysis. We evaluated the framework using four common industrial contaminants and applied it to groundwater samples from a petrochemical plant. Cell-based assays identified the samples with potential liver and kidney toxicity, evidenced by high cytotoxicity, increased mitochondrial reactive oxygen species (ROS) production, apoptosis, and endocrine-disrupting effects, such as altered steroid hormone production. ToxPi analysis integrated the results from multiple endpoints to generate composite scores and enabled the systematic ranking of groundwater samples according to their overall potential risk. Our findings demonstrate that combining HTS/HCS assays with mechanistic insights from AOPs and computational analysis provides a comprehensive and efficient strategy for groundwater toxicity screening, supporting more effective environmental monitoring and public health protection.
PMID:40773838 | DOI:10.1016/j.jhazmat.2025.139432
J Hazard Mater. 2025 Aug 5;496:139447. doi: 10.1016/j.jhazmat.2025.139447. Online ahead of print.
ABSTRACT
Bisphenol A (BPA), a persistent endocrine disruptor, poses critical water treatment challenges. In this study, cubic catalysts dominated by {100} crystal facets (i@Co@CeO2 CNs) were synthesized via crystal surface engineering combined with a cobalt (Co) impregnation strategy. This approach aimed to enhance activation of peroxymonosulfate (PMS) for the degradation of BPA by modulating the exposed crystal facets of cerium dioxide (CeO2) carriers. The {100} facets exhibited enhanced oxygen vacancies (Ov) (Oβ: 29.57 %) and Co dispersion (0.58 at%), achieving 93 % BPA removal within 120 min (k = -0.0184 min⁻¹)-15.3 × faster than {111}-faceted systems. The system maintained > 85 % efficiency across pH 2-10 and resisted anion interference (Cl⁻/SO₄²⁻), retaining > 80 % activity. Radical quenching and EPR identified •OH, SO4•⁻, and O2•⁻ as dominant oxidants (>75.2 % contribution). DFT calculations revealed strong PMS chemisorption (Eads = -3.17 eV) on {100} facets, enabling targeted electron injection into O-O σ* orbitals that weakened O-O bonds (lowest cleavage barrier: 1.01 eV). Toxicity assessment confirmed intermediates had orders-of-magnitude lower acute toxicity than BPA, with progressive mineralization (40.6 % TOC removal in 120 min) to CO₂/H₂O. This work demonstrates crystal facet engineering as a novel strategy for designing eco-efficient water remediation catalysts.
PMID:40773843 | DOI:10.1016/j.jhazmat.2025.139447
J Steroid Biochem Mol Biol. 2025 Aug 6;254:106840. doi: 10.1016/j.jsbmb.2025.106840. Online ahead of print.
ABSTRACT
Polycystic Ovary Syndrome (PCOS) is a severe and heterogeneous endocrine disorder affecting 6-20 % of women of reproductive age globally. Despite its high prevalence, the underlying etiology and pathophysiology remain unclear, necessitating the use of animal models to study disease mechanisms and therapeutic targets. This review critically evaluates various induction agents used in PCOS animal models and their ability to mimic the clinical, metabolic, and reproductive manifestations of the human condition. Induction agents explored include androgens [Testosterone, Dihydrotestosterone (DHT), Dehydroepiandrosterone (DHEA)], estrogen (estradiol valerate), aromatase inhibitors (letrozole), endocrine disruptors (bisphenol A), and dietary modifications (high-fat or high-sugar diets). These agents, administered in species such as rats, mice, zebrafish, reproduce hallmark PCOS features, including hyperandrogenism, anovulation, polycystic ovaries, and insulin resistance. The review highlights the mechanisms, symptom profiles, and translational relevance of each model. Comparative analysis is provided to assess the strengths and limitations associated with each agent, considering factors such as hormonal balance, metabolic function, and reproductive outcomes. Animal models serve as essential tools for understanding PCOS and testing therapeutic interventions. Each inducing agent offers unique insights into specific aspects of the disorder, although none fully replicates the human syndrome. The selection of the agent and animal species based on research goals is vital for clinical relevance. Future work should focus on integrating models that reflect both reproductive and metabolic features of PCOS to improve translational value.
PMID:40774400 | DOI:10.1016/j.jsbmb.2025.106840
Food Chem Toxicol. 2025 Aug 5;205:115687. doi: 10.1016/j.fct.2025.115687. Online ahead of print.
ABSTRACT
BACKGROUND: Depression may be influenced by environmental factors, including phthalate exposure as endocrine-disrupting chemicals (EDCs). Gut microbiota may modulate phthalate toxicity, and probiotics have been shown to alleviate depressive symptoms; however, their interrelationship remains unclear.
METHODS: This cross-sectional study included 7999 participants from the 2005-2018 National Health and Nutrition Examination Survey (NHANES). Data on probiotic/yogurt consumption, urinary phthalate metabolites, depressive symptoms (measured by PHQ-9), and covariates were collected. Weighted generalized linear models (W-GLM) were employed to elucidate variable associations. Mediation analyses assessed whether phthalates mediated the association between probiotic/yogurt consumption and depressive symptoms. Similarly, subgroup analyses were conducted to elucidate sex-specific differences.
RESULTS: The data revealed that probiotic/yogurt consumption was significantly associated with lower PHQ-9 scores. Furthermore, probiotic/yogurt consumption was inversely associated with urinary MBzP and MiBP levels, with MiBP mediating 7 % of its association with depressive symptoms. Multiple-group mediation analysis showed that the mediating effect was significant in females only, indicating possible sex-specific mechanisms.
CONCLUSIONS: Probiotic/yogurt consumption may be linked to reduced depressive symptoms via lowered phthalate exposure, particularly MiBP. Phthalates affect females more than males, suggesting sex-specific susceptibility to EDCs. Further studies are required to validate the underlying molecular mechanisms.
PMID:40774406 | DOI:10.1016/j.fct.2025.115687
Clin Chim Acta. 2025 Aug 5;578:120534. doi: 10.1016/j.cca.2025.120534. Online ahead of print.
ABSTRACT
The detection of 17β-estradiol (E2), a potent endocrine-disrupting compound, is critical for both environmental monitoring and biomedical diagnostics. Traditional detection methods often suffer from limitations in sensitivity, selectivity, and cost-effectiveness. Aptasensors, which utilize aptamers as biorecognition elements, offer promising alternatives because of their high specificity, stability, and adaptability. This paper explores recent advancements in aptasensor technologies for E2 detection, highlighting optical, electrochemical, and surface-enhanced Raman scattering (SERS)-based platforms. The integration of nanomaterials such as gold nanoparticles, carbon dots, and conductive polymers significantly enhances sensor performance, achieving ultralow detection limits and broad dynamic ranges. By leveraging these innovations, aptasensors provide scalable solutions for real-time monitoring of E2 in environmental, food, and clinical samples, paving the way for improved endocrine regulation and public health safety.
PMID:40774446 | DOI:10.1016/j.cca.2025.120534
Reprod Toxicol. 2025 Aug 6;137:109023. doi: 10.1016/j.reprotox.2025.109023. Online ahead of print.
ABSTRACT
BACKGROUND: Brominated flame retardants (BFRs) are endocrine-disrupting contaminants; however, the impact of BFR mixtures on sex steroid hormone levels in adults remains unclear.
METHODS: This study included 2513 male and female adults from the 2013-2016 National Health and Nutrition Examination Survey (NHANES). Weighted linear regression was employed to examine the associations between individual BFR exposures and total testosterone(TT), estradiol(E2), sex hormone binding globulin (SHBG), free androgen index (FAI), and TT/E2. The generalized additive model (GAM) was used to explore the nonlinear associations between BFRs and sex steroid hormones. Additionally, weighted quantile sum (WQS) regression and Quantile G-computation (QGC) were applied to evaluate the overall effects of BFRs mixtures on these five sex hormone biomarkers and to identify key contributing chemicals. We also explored potential effect modifications by age, BMI and educational level.
RESULT: The weighted linear regression results indicated that, after adjusting for covariates, PBDE209 was significantly negatively associated with SHBG in males (β = -8.495, 95 % CI: -15.915, -1.073), while PBB153 and PBDE85 were negatively associated with female TT/E2 (β = -0.718, 95 % CI: -1.362, -0.075) and E2 (β = -2.910, 95 % CI: -5.126, -0.693), respectively. The Generalized Additive Model (GAM) revealed nonlinear associations between certain BFRs and TT, E2, FAI, and TT/E2 in both males and females. WQS regression analysis showed a significant negative association between the WQS index and male SHBG (β = -1.919, 95 % CI: -3.706, -0.133), which was consistent with the results from the weighted linear regression. However, no significant associations were observed between mixed BFR exposure and female sex hormone levels. Further confirmation of the WQS regression findings was provided by QGC analysis. Notably, PBDE209 was identified as the primary BFR influencing SHBG levels.
CONCLUSION: Exposure to mixed BFRs significantly affects SHBG levels in adult males, while no significant impact on sex steroid hormone levels was observed in adult females. Further studies are required to evaluate the potential long-term health consequences.
PMID:40774634 | DOI:10.1016/j.reprotox.2025.109023