BMC Womens Health. 2025 Oct 14;25(1):491. doi: 10.1186/s12905-025-04051-0.
ABSTRACT
INTRODUCTION: Breast cancer is the predominant malignancy among women globally and is a major contributor to cancer-related mortality in Pakistan, where one in nine women is affected. Recent data indicate that endocrine-disrupting chemicals (EDCs) in personal care products may increase the risk of breast cancer. However, our understanding of these carcinogenic risks remains limited. This study assessed the awareness of breast cancer risk factors, including the role of personal care products, among female medical students at Jinnah Sindh Medical University, Karachi.
METHODOLOGY: This cross-sectional study included 381 female undergraduate MBBS students (mean age: 20.1 ± 1.3 years) at Jinnah Sindh Medical University. Data were collected through a structured and pilot-tested questionnaire validated with Cronbach's alpha of 0.721, comprising sociodemographic details, awareness of breast cancer risk factors and screening methods, usage patterns of personal care products, and knowledge of EDCs. Descriptive statistics and chi-square tests were used to analyze the data, with a significance threshold of p ≤ 0.05.
RESULTS: Among the participants, 87.1% indicated that exposure to chemicals in cosmetics was a probable risk factor. Sunscreens (77.2%), deodorants (69.3%), and moisturizers (64.8%) exhibited the highest daily usage rates. Only 39.9% of respondents were aware that these products contained EDCs. Recommendations from beauticians (p = 0.001), doctors (p = 0.041), and social media (p = 0.017) significantly influenced the purchasing decisions. Only 35.4% conducted independent investigations of substances, while 79.3% endorsed legislative measures against carcinogens in cosmetics.
CONCLUSION: This study highlights that future doctors possess limited knowledge about breast cancer, especially concerning environmental risk factors, such as endocrine-disrupting chemicals (EDCs) in personal care products. While it does not establish a causal relationship, the study underscores significant gaps in the participants' understanding.
PMID:41088134 | DOI:10.1186/s12905-025-04051-0
Clin Endocrinol (Oxf). 2025 Oct 14. doi: 10.1111/cen.70050. Online ahead of print.
ABSTRACT
OBJECTIVE: To clarify the link between environmental pollution and diabetes risk by focusing on pancreatic β-cells as key targets of environmental insults, with emphasis on the role of endocrine-disrupting chemicals (EDCs) in pancreatic dysfunction and diabetes pathogenesis.
METHODS: This narrative review synthesises recent research on EDCs, focusing on their effects on β-cells. The literature search included studies in English on EDCs, diabetes, and β-cell function, utilising Boolean operators to refine the search.
RESULTS: EDCs impair β-cell function through mechanisms such as oxidative stress, mitochondrial damage, and epigenetic changes. These pollutants disrupt insulin synthesis, secretion, and β-cell survival, which is distinct from their general metabolic effects. Additionally, EDCs may interact synergistically with traditional diabetes risk factors, such as high-fat diets, amplifying the risk of diabetes.
CONCLUSION: Environmental pollutants play a significant role in β-cell dysfunction and diabetes, offering new directions for research and prevention.
PMID:41088529 | DOI:10.1111/cen.70050
Front Oncol. 2025 Sep 29;15:1682794. doi: 10.3389/fonc.2025.1682794. eCollection 2025.
ABSTRACT
Chromatin domain-binding protein 4 (CHD4), the ATPase core component of the NuRD complex, exerts dual roles in epigenetic regulation-mediating both gene silencing and activation. We report a case of occult breast cancer with extensive bone metastasis harboring a novel somatic truncation mutation in the catalytic SNF2 domain (CHD4 p.Trp736Ter). This mutation, unreported in other cancers to date, abolishes ATPase activity and disrupts NuRD complex assembly. Multimodal analysis (PET/CT, biomarkers, pathology) confirmed the case as luminal-A subtype and revealed a significant response to endocrine therapy. We hypothesize that this CHD4 mutation may alter the protein's dual regulatory balance, particularly enhancing its potential gene-activating functions, and propose that impaired chromatin remodeling driven by such mutations is associated with metastatic progression of breast cancer.
PMID:41089506 | PMC:PMC12515663 | DOI:10.3389/fonc.2025.1682794
Anim Cells Syst (Seoul). 2025 Oct 11;29(1):598-614. doi: 10.1080/19768354.2025.2569881. eCollection 2025.
ABSTRACT
Bisphenol A (BPA) is a widely used xenoestrogen that can disrupt neuroendocrine and immune regulation through multiple hormone receptors. This study investigated BPA-induced long non-coding RNA (lncRNA)-mRNA interactions in the cerebral cortex and hypothalamic-pituitary-thyroid (HPT) axis of adult male mice. Transcriptome sequencing and comprehensive lncRNA annotation identified 14,858 novel lncRNA transcripts. Integrated network analysis using weighted gene co-expression network analysis (WGCNA) revealed four distinct tissue-specific modules: neuronal signaling alterations (Tac1, Htr1b, Npy), RNA splicing modifications (Srsf5), PI3K/Akt-mediated cellular dysfunction (Creb5, Cdkn1a), and immune receptor signaling disruptions (Trbv15, Fcrla). These findings suggest that BPA reprograms transcriptional networks in a tissue-specific manner, potentially disrupting hormone-related neurotransmission, metabolic regulation, and immune signaling via lncRNA-mediated mechanisms. Such systems-level reprogramming of the immune-neuroendocrine network (INEN) provides novel mechanistic insights and biomarker candidates for assessing and mitigating the health impacts of environmental endocrine disruptors.
PMID:41090079 | PMC:PMC12517422 | DOI:10.1080/19768354.2025.2569881
Ecotoxicology. 2025 Oct 14. doi: 10.1007/s10646-025-02982-w. Online ahead of print.
NO ABSTRACT
PMID:41085888 | DOI:10.1007/s10646-025-02982-w
Environ Pollut. 2025 Oct 12:127252. doi: 10.1016/j.envpol.2025.127252. Online ahead of print.
ABSTRACT
Botanical pesticides are increasingly promoted as environmentally benign alternatives to synthetic chemicals in integrated pest management. However, the ecological safety of their persistent ultra-low residues remains poorly understood, particularly regarding non-target natural predators. In this study, we investigated the chronic toxicological effects of an ultra-low concentration (ULC; 1/100 of LC30 of 15.106 mg/mL) of a botanical pesticide mixture-composed of commercially available tea saponin and matrine mixed at a ratio of 10:1 (v:v)-on the generalist Propylea japonica. Long-term exposure significantly prolonged larval development, reduced pupal mass, and compromised female fecundity, indicating potential disruptions to population stability and biocontrol efficacy. Gene expression analyses revealed stage-specific alterations in detoxification and hormone-related pathways: fourth-instar larvae exhibited elevated expression of GST and DuoX, downregulation of JHAMT1 and PjIRS1, and upregulation of EcR, whereas adult females showed marked suppression of JHDK, FOXO, PjIRS1, and Vg. These changes point to endocrine disruption and impaired reproductive capacity. Moreover, 16S rRNA sequencing revealed that ULC exposure significantly decreased microbial diversity and altered symbiont composition, particularly in adult beetles. Collectively, our findings demonstrate that even ultra-low residues of botanical pesticides can impose sublethal physiological stress and reshape symbiotic microbial communities in beneficial insects. This work underscores the need for refined ecological risk assessments of green pesticides and advocates for pest management strategies that balance effective control with the conservation of natural enemies.
PMID:41086911 | DOI:10.1016/j.envpol.2025.127252
Rapid Commun Mass Spectrom. 2026 Jan;40(1):e10155. doi: 10.1002/rcm.10155.
ABSTRACT
RATIONALE: Phenolic endocrine-disrupting chemicals (EDCs), including alkylphenols (APs) and bisphenols (BPs), pose significant environmental and public health concerns due to their widespread presence in aquatic ecosystems and potential toxicity at trace concentrations. This study developed and validated a sensitive analytical method for the simultaneous determination of 16 phenolic EDCs in environmental waters.
METHODS: The method involves sample acidification to pH 2, hydrophilic-lipophilic balance (HLB), solid-phase extraction (SPE), and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis with negative electrospray ionization (ESI-). Systematic optimization revealed that an alkaline mobile phase (methanol/0.1% ammonia) significantly enhanced the ionization efficiency of phenolic compounds, improving sensitivity by approximately an order of magnitude compared to acidic conditions. Chromatographic separation was optimized using an ACQUITY UPLC BEH C18 column, which provided superior peak shapes and improved retention of hydrophobic compounds.
RESULTS: Acidification of samples prior to SPE was critical for maximizing analyte recovery (57.9%-94.2%). The validated method demonstrated outstanding analytical performance, achieving low detection limits (0.01-0.4 ng/L), excellent linearity (R = 0.991-0.999) across a broad concentration range (1.0-50.0 μg/L) and high precision (RSDs = 1.3%-13.6%). Application of the method to environmental samples collected from rivers, wastewater treatment plants, and landfill leachates identified eight target compounds, with alkylphenols detected at higher concentrations than BPs.
CONCLUSION: This reliable and robust method provides a valuable tool for monitoring trace levels of phenolic EDCs in diverse aquatic environments, supporting technically comprehensive environmental assessments and regulatory compliance.
PMID:41087191 | DOI:10.1002/rcm.10155
Naunyn Schmiedebergs Arch Pharmacol. 2025 Oct 15. doi: 10.1007/s00210-025-04629-3. Online ahead of print.
ABSTRACT
Epoxy resin is the precursor of bisphenol A and is an important component in a wide range of daily used products. It produces toxic effects by oxidative stress, inflammation and endocrine disruption. Its exposure to humans occur through inhalation, dermal contact and ingestion. Several studies link the epoxy resin components to reproductive toxicity including impaired ovarian function and hormonal imbalance in males and females. The study was aimed to assess the reproductive toxicity in female rats due to epoxy resin exposure and demonstrate the curative potential of resveratrol and pterostilbene against epoxy resin-induced reproductive toxicity. The study included eight groups of rats (n = 6). One was the control group receiving only vehicle, while the other one was the epoxy resin-treated group in which the female rats were given orally epoxy resin at 15 mg/kg/day for 4 weeks. Other six groups were administered resveratrol and pterostilbene orally at different doses (50, 25 and 12.5 mg/kg/day) for 4 weeks. Dose selection was performed according to the previously published data. After the study duration, female rats were ovariectomized and assessed for body weight changes, oxidative stress and histopathological changes. ELISA analysis was performed for inflammatory markers in ovaries while caspase-3 gene was evaluated in ovaries by PCR. Statistical comparison was performed by one-way ANOVA followed by Tukey's post hoc test. The subsequent treatment with resveratrol and pterostilbene depicted marked improvements in LH, FSH, estrogen, progesterone and testosterone levels. The female rats exposed to epoxy resin showed a high content of the caspase-3 gene responsible for apoptosis. Moreover, the oxidative stress markers such as SOD, CAT and GSH were increased while MDA decreased in the ovary of rats treated with resveratrol and pterostilbene, whereas anti-inflammatory markers such as TNF-α and NF-κB were increased significantly with the epoxy resin exposure but treatment drugs employed reduction in their levels significantly. It was concluded that epoxy resin produced marked damage to the ovary and this toxicity can be reduced with resveratrol and pterostilbene treatments.
PMID:41087713 | DOI:10.1007/s00210-025-04629-3
Sage Open Pediatr. 2025 Oct 8;12:30502225251380331. doi: 10.1177/30502225251380331. eCollection 2025 Jan-Dec.
ABSTRACT
Pediatric neurological disorders such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are increasingly understood to arise from complex interactions between genetics and environmental factors. Emerging evidence highlights the role of epigenetic mechanisms, particularly DNA methylation, histone modification, and non-coding RNAs, in mediating how early-life exposures shape brain development. This review synthesizes findings from 48 recent studies, including human cohorts and animal models, linking prenatal stress, maternal nutrition, endocrine disruptors, and air pollution to epigenetic alterations that disrupt neurogenesis, synaptic plasticity, and neural differentiation. These mechanisms offer insight into clinical phenomena and open potential for early screening and epigenetic interventions in pediatric neurology. The main finding reveals that early environmental exposures can leave lasting epigenetic marks that significantly influence neurodevelopment and contribute to pediatric neurological disorders.
PMID:41084638 | PMC:PMC12515299 | DOI:10.1177/30502225251380331
Front Microbiol. 2025 Sep 25;16:1630636. doi: 10.3389/fmicb.2025.1630636. eCollection 2025.
ABSTRACT
Steroid estrogens, including the naturally occurring hormones estrone (E1), estradiol (E2), and estriol (E3), as well as the synthetic estrogen ethinylestradiol (EE2), play essential physiological roles in the regulation of the reproductive systems and development of secondary sex characteristics in humans and animals. Environmental pollution with steroid estrogens is gaining rising concerns worldwide due to their endocrine-disrupting and carcinogenic properties, which can harm humans and aquatic organisms. Hence, efficient removal of these compounds, particularly from wastewater, is deemed key to prevent environmental pollution with estrogens. Although several physicochemical treatments contribute to estrogen elimination from wastewater treatment plants (WWTPs), biological treatment via microbial biodegradation remains the most efficient estrogen removal approach. Several estrogen-degrading/transforming bacteria were isolated mainly from activated sludge samples collected from WWTPs. Moreover, biochemical, and molecular aspects for estrogen degradation pathways were revealed recently for estrone and estradiol. On the contrary, less knowledge is currently available for E3 and EE2 biodegradation pathways. Despite high structural similarity among steroid estrogens, they can be degraded via a diversity of biodegradation and biotransformation pathways. Nonetheless, these pathways exhibit common as well as unique biochemical and molecular features. Moreover, steroid estrogens are interconvertible, which can affect their environmental concentrations, and hence, their persistence/biodegradability. In this review, we present and discuss the various steroid estrogen biodegradation and biotransformation pathways, with a focus on the biochemical aspects. Furthermore, we highlight some of the known abiotic estrogen reactions and the recent discoveries on microbial estrogenesis and envisage how they can affect estrogen susceptibility to microbial degradation.
PMID:41078513 | PMC:PMC12507874 | DOI:10.3389/fmicb.2025.1630636
Front Immunol. 2025 Sep 26;16:1625087. doi: 10.3389/fimmu.2025.1625087. eCollection 2025.
ABSTRACT
Depressive disorders exhibit significant comorbidity with lipid dysregulation. Clinical observations indicate that poor lifestyle factors contribute to lipid dysregulation in depressed patients. This dysregulation disrupts gut microbiota homeostasis and endocrine balance. Mitochondria and endoplasmic reticulum, critical organelles for lipid metabolism, also show impaired homeostasis in depression, further contributing to lipid dysregulation. Such alterations activate peripheral and central immune-inflammatory responses, compromise blood-brain barrier integrity, and disrupt neuroimmune cytokine signaling. This process induces and aggravates neuroinflammation, thereby contributing to the onset and progression of depressive disorders. These disruptions in homeostasis further exacerbate lipid dysregulation. This review delineates the molecular mechanisms by which dysregulation of lipid metabolism exacerbates depressive disorders via neuroinflammatory pathways, offering critical insights into pathogenesis and therapeutic strategies.
PMID:41080588 | PMC:PMC12510854 | DOI:10.3389/fimmu.2025.1625087
Front Cell Dev Biol. 2025 Sep 25;13:1670716. doi: 10.3389/fcell.2025.1670716. eCollection 2025.
ABSTRACT
The skeleton functions as an endocrine organ. Osteocytes maintenance of skeletal strength and energy balance by sensing mechanical stress and communicating with surrounding cells. They are currently considered key regulators of bone remodeling, mineral metabolism, and systemic homeostasis. Osteocytes originate from osteoblasts and are embedded in the lacunar-tubular network. They express proteins such as DMP1, sclerostin, and FGF23, and influence Wnt signaling, the RANKL/OPG axis, and phosphate metabolism. We review the latest studies in the field of osteocyte biology, focusing on their mechanotransduction through Piezo1 and integrins, regulation of osteoclastogenesis and osteogenesis, and their interactions with the bone marrow microenvironment, including immune and vascular cells. In osteoporosis, osteocyte dysfunction is manifested by apoptosis, ferroptosis, and pyroptosis. These changes, together with altered secretion, lead to uncoupled remodeling, disruption of the lacuno-canalicular network and metabolic imbalances that are intertwined with inflammation and bone marrow fat deposition. Osteocytes play an important role in fracture healing and adaptive remodeling under mechanical stimulation, promoting angiogenesis and stem cell recruitment. A growing number of emerging approaches, including stem cell therapy, CRISPR editing, and AI-driven multi-omics for precision medicine, are accelerating osteocyte-related research and the development of therapeutic strategies. These studies reveal the clinical potential of osteocyte-targeted therapies to prevent osteoporosis, improve bone strength, and enhance regeneration. By integrating molecular, cellular, and systems knowledge, we highlight osteocytes as a key therapeutic target to combat bone diseases and promote bone regeneration.
PMID:41081044 | PMC:PMC12508660 | DOI:10.3389/fcell.2025.1670716
Reprod Toxicol. 2025 Oct 11:109081. doi: 10.1016/j.reprotox.2025.109081. Online ahead of print.
ABSTRACT
Polycyclic aromatic hydrocarbons (PAHs) and phthalates (PAEs) exert endocrine-disrupting effects; however, research investigating the relationship between co-exposure to these two classes of pollutants and sex hormone levels in pregnant women remains limited. To address this gap, we enrolled 454 women in early pregnancy from the Zunyi Birth Cohort (ZBC) and used linear mixed-effects models (LMM), Bayesian kernel machine regression (BKMR), and restricted cubic spline (RCS) models to examine associations between early-pregnancy both individual and combined exposur to PAHs and PAEs and maternal estradiol levels. LMM results revealed no significant associations between PAH metabolites and estradiol, but significant associations between PAE metabolites and estradiol-primarily driven by monoisobutyl phthalate (MIBP) and monobutyl phthalate (MBP), with corresponding β values (95% confidence intervals [CIs]) of -534.77 (-761.17, -308.37) and 473.19 (233.80, 712.58), respectively. BKMR analyses showed that exposure to PAH metabolites alone was negatively associated with estradiol, primarily involving 4-hydroxyphenanthrene (4-OHPH) and 1-hydroxypyrene (1-OHPYR). Exposure to PAE metabolites alone was also negatively associated with estradiol, driven mainly by monoethyl phthalate (MEP), MIBP, and MBP. Concurrent exposure to PAE and PAH metabolites was negatively associated with estradiol, with key contributors including 2-hydroxyfluorene (2-OHFLU), MiBP, MBP, mono(2-ethylhexyl) phthalate (MEHP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP). RCS results demonstrated an inverted U-shaped relationship between 2-OHFLU and estradiol (F=2.8, P=0.019), a non-linear negative association between MIBP and estradiol (F=3.3, P=0.002), and an inverted U-shaped relationship between MEOHP and estradiol (F=4.4, P=0.005). Collectively, these findings indicate that both individual and combined exposure to PAHs and PAEs in early pregnancy is associated with estradiol levels in pregnant women, with evidence of exposure-response relationships. Reducing exposure to PAH and PAE metabolites in early pregnancy is recommended to further safeguard maternal and fetal health.
PMID:41083018 | DOI:10.1016/j.reprotox.2025.109081
Comp Biochem Physiol C Toxicol Pharmacol. 2025 Oct 11:110371. doi: 10.1016/j.cbpc.2025.110371. Online ahead of print.
ABSTRACT
Dibutyl phthalate (DBP), a ubiquitous environmental contaminant, has been shown to induce developmental toxicity and thyroid hormone disruption in aquatic organisms. In this study, we evaluated the protective effects of the natural astaxanthin (AST) against DBP-induced toxicity in early-life stage zebrafish. Exposure to DBP (0.1-1 mg/L) significantly impaired embryonic development, reduced body length and weight, and disrupted thyroid hormone homeostasis by decreasing T4 and increasing T3 levels. These effects were accompanied by oxidative stress, inflammation, and dysregulated expression of key genes along the hypothalamic-pituitary-thyroid (HPT) axis, including dio2, tg, crhβ, and tsh. AST supplementation dose-dependently alleviated these developmental and thyroid hormone disruption, restored redox balance and anti-inflammatory responses, and normalized HPT axis gene expression. Molecular docking identified strong binding affinities between AST and core regulatory targets (HSP90AB1, HIF1A, MTOR, NFKB1), demonstrating its multi-target mechanism involving oxidative stress mitigation, metabolic regulation, and immune modulation. These findings provide new insight into AST's protective role against endocrine-disrupting pollutants and suggest its potential application in aquatic toxicology and human health.
PMID:41083114 | DOI:10.1016/j.cbpc.2025.110371
Ecotoxicol Environ Saf. 2025 Oct 11;305:119140. doi: 10.1016/j.ecoenv.2025.119140. Online ahead of print.
ABSTRACT
Cadmium (Cd), as a widespread environmental pollutant, poses a persistent threat to reproductive health due to its biological half-life of 30 years and endocrine-disrupting properties. Epidemiological studies have associated Cd exposure with adverse pregnancy outcomes such as spontaneous abortion (SA), although the underlying molecular mechanisms are largely unexplored. Decidualization is a critical process for embryo implantation and the maintenance of pregnancy. Impaired decidualization directly leads to spontaneous abortion. In this study, multi-element quantification in decidual tissues demonstrated significantly higher Cd concentrations in SA patients compared to normal controls, suggesting local Cd accumulation as a potential contributor to decidual dysfunction. Based on proteomic analysis of uterine Cd-exposed mouse models, we identified downregulation of F-box protein FBXO2, a key regulator of ubiquitination, which was further validated in decidual tissues from SA patients. Utilizing in vitro Cd-exposed stromal cell models and in vivo Cd-induced SA mouse model, we demonstrated that FBXO2 expression increases progressively during decidualization, whereas Cd exposure downregulates FBXO2 and its downstream IL6ST/STAT3 signaling axis, concomitant with impaired decidualization. Notably, FBXO2 overexpression enhanced K63-linked ubiquitination of IL6ST concomitant with restoration of STAT3 signaling, thereby rescuing Cd-induced suppression of decidualization markers PRL, IGFBP1, and FOXO1. Taken together, the results of our study predict potential Cd-binding sites on the FBXO2 protein and demonstrate that Cd disrupts decidualization by suppressing FBXO2 and its downstream IL6ST/STAT3 signaling, ultimately contributing to pathogenesis of SA.
PMID:41076860 | DOI:10.1016/j.ecoenv.2025.119140
Environ Pollut. 2025 Oct 10:127223. doi: 10.1016/j.envpol.2025.127223. Online ahead of print.
ABSTRACT
Microplastic (MP) and nanoplastic (NP) pollution has permeated virtually all aspects of life on earth - from high altitude clouds and arctic ice cores to single celled algae and unborn fetuses. Compared to MPs, the ability of NPs to infiltrate biological barriers such as the blood-brain and testes barriers is concerning to human health. Evidence of accumulation across human tissues has accrued, but the long-term health consequences are not well understood. Previously, we exposed zebrafish larvae to environmentally relevant doses of NPs (0 -10,000 parts per billion) for five days during early development, reporting NP accumulation, hyperactivity, and disruption of neuromuscular, metabolic, and epigenetic pathways immediately post-exposure. Here, we reared these developmentally exposed animals to adulthood, assessing reproductive capacity, offspring neurobehavior, and transcriptomics of brain and gonadal tissue for comparison. NP exposure impaired reproduction in adulthood: while high level exposure profoundly reduced overall spawning capacity, intermediate exposure also decreased fertilization of elicited eggs. Surviving offspring from the intermediate group were also hyperactive, like their parents, demonstrating a persistent and heritable neurobehavioral phenotype. Overall, far more significantly differentially expressed genes were found in adult tissues than in larvae; however, larval disruption of endocrine and neurological disease pathways persisted into adulthood. While female transcriptomics suggested recovery from early life NP exposure, male tissues were deleteriously and disproportionately affected. Male transcriptomics implicated neuromuscular and neurodegenerative diseases, endocrine disruption, and cancer. Oxidative stress was a consistently present mechanism underlying persistent disruption and adult-onset pathologies.
PMID:41077166 | DOI:10.1016/j.envpol.2025.127223
Environ Pollut. 2025 Oct 10:127223. doi: 10.1016/j.envpol.2025.127223. Online ahead of print.
ABSTRACT
Microplastic (MP) and nanoplastic (NP) pollution has permeated virtually all aspects of life on earth - from high altitude clouds and arctic ice cores to single celled algae and unborn fetuses. Compared to MPs, the ability of NPs to infiltrate biological barriers such as the blood-brain and testes barriers is concerning to human health. Evidence of accumulation across human tissues has accrued, but the long-term health consequences are not well understood. Previously, we exposed zebrafish larvae to environmentally relevant doses of NPs (0 -10,000 parts per billion) for five days during early development, reporting NP accumulation, hyperactivity, and disruption of neuromuscular, metabolic, and epigenetic pathways immediately post-exposure. Here, we reared these developmentally exposed animals to adulthood, assessing reproductive capacity, offspring neurobehavior, and transcriptomics of brain and gonadal tissue for comparison. NP exposure impaired reproduction in adulthood: while high level exposure profoundly reduced overall spawning capacity, intermediate exposure also decreased fertilization of elicited eggs. Surviving offspring from the intermediate group were also hyperactive, like their parents, demonstrating a persistent and heritable neurobehavioral phenotype. Overall, far more significantly differentially expressed genes were found in adult tissues than in larvae; however, larval disruption of endocrine and neurological disease pathways persisted into adulthood. While female transcriptomics suggested recovery from early life NP exposure, male tissues were deleteriously and disproportionately affected. Male transcriptomics implicated neuromuscular and neurodegenerative diseases, endocrine disruption, and cancer. Oxidative stress was a consistently present mechanism underlying persistent disruption and adult-onset pathologies.
PMID:41077166 | DOI:10.1016/j.envpol.2025.127223
Curr Opin Insect Sci. 2025 Oct 10:101451. doi: 10.1016/j.cois.2025.101451. Online ahead of print.
ABSTRACT
Global insect populations are declining at an alarming rate, threatening biodiversity and the ecosystem services on which humans depend. One potential driver of this decline is the alteration of key biological functions, including parental care, by anthropogenic factors such as chemical pollution and exposure to endocrine-disrupting compounds (EDCs). This review synthesizes current knowledge on how EDCs may affect insect parental care, highlighting major gaps and opportunities for research. We first discuss the taxonomic bias in EDC research and its implications for understanding insect susceptibility. We then summarize what is known about the hormonal regulation of insect parental care, emphasizing that current knowledge is limited to a few species, a few behaviours, and primarily juvenile hormone. Next, we examine the sparse evidence for direct or indirect effects of chemical pollutants on parental behaviors. Finally, we propose five research priorities to elucidate the interplay between EDC exposure, hormonal regulation, and parental care in insects: clarifying hormonal mechanisms, applying unbiased -omics approaches combined with functional analyses, identifying EDCs most likely to disrupt care, expanding taxonomic and behavioral coverage, and linking individual-level effects to population outcomes. Addressing these priorities is timely to establish causal links between hormones, behaviour, and pollutants, providing essential insights to predict and mitigate the impacts of EDCs on insect populations, ecosystem functioning, and evolutionary dynamics.
PMID:41077223 | DOI:10.1016/j.cois.2025.101451
Sci Total Environ. 2025 Oct 10;1003:180658. doi: 10.1016/j.scitotenv.2025.180658. Online ahead of print.
ABSTRACT
Polychlorinated naphthalenes (PCNs) are a class of persistent organic pollutants (POPs) that can exhibit high environmental persistence, bioaccumulation properties and significant toxicological effects. Historically, PCNs have been used as insulators and fire retardants in various electrical and industrial applications due to their stability and compatibility. Despite the implementation of global regulatory initiatives such as the 'phase-out policy' and Stockholm Convention on POPs, their legacy contamination and ongoing emissions continue to pose environmental and public health risks, especially in Asia. This review investigated current knowledge on the sources, occurrences and health impacts of PCNs in rapidly developing and densely populated urban Asian regions. Our findings indicate that metallurgy industries are the major source of PCNs, contributing over 97 % of total emissions, followed by thermal processes, historical usage and emerging concerns of electronic waste recycling activities. Lower chlorinated PCN congeners (mono to tetra) levels were found to vary significantly from fg to ng levels in environmental distribution, contributing to the extensive contamination of air, soil, water, sediments and biota samples in proximity to industrial areas. Occupational exposure was associated with increased cancer risks (CR), while elevated non-CR were observed in vulnerable populations such as infants and children. Ingestion was the primary exposure route, occurring through consumption of PCNs contaminated food. PCNs exposure showed potential health risks including carcinogenicity, neurotoxicity, endocrine disruption and reproductive disorders. This review highlights the need for further research on emerging potential sources, longitudinal environmental monitoring and epidemiological studies to evaluate health impacts of PCN exposures in Asian regions.
PMID:41075568 | DOI:10.1016/j.scitotenv.2025.180658
Toxicology. 2025 Oct 9:154301. doi: 10.1016/j.tox.2025.154301. Online ahead of print.
ABSTRACT
The integrated assessment of estrogenic and androgenic endocrine disruption using a combination of receptor dimerization and transactivation assays is an effective approach for providing information the mechanistic action of chemical compounds that disrupt estrogen and androgen signaling pathways at the cellular level. This study integratedly evaluated the estrogenic and androgenic endocrine-disrupting properties of a total of 29 chemicals, including representative bisphenols, phthalates, and biocides, which are commonly exposed to humans. As a result, most bisphenols showed estrogenic agonist activity through transactivation via dimerization of estrogen receptors alpha and beta, while also exhibiting androgenic antagonist activity by inhibiting dihydrotestosterone-induced transactivation through interference with androgen receptor dimerization. Most phthalates also exhibited estrogenic agonist activity through transactivation via dimerization of estrogen receptors alpha and beta, and only some of them showed androgenic antagonist activity by interfering with androgen receptor dimerization and inhibiting dihydrotestosterone-induced transactivation. Biocides showed estrogenic and androgenic endocrine-disrupting properties through various mechanisms depending on their structural diversity. This integrated assessment effectively provided clues to the mechanism of action of endocrine-disrupting chemicals in estrogen and androgen signaling pathways at the cellular level, based on the adverse outcome pathway framework.
PMID:41075969 | DOI:10.1016/j.tox.2025.154301
Immunol Lett. 2025 Oct 9:107102. doi: 10.1016/j.imlet.2025.107102. Online ahead of print.
ABSTRACT
Prevalence of allergic diseases has increased globally, reflecting environmental and behavioral changes. The exposome concept encompasses cumulative chemical, microbial, nutritional, psychosocial, and physical exposures across the life course, offering a unifying framework to understand how immune tolerance is shaped or disrupted. Emerging evidence highlights that early-life exposures are particularly critical. Pollutants, endocrine disruptors, microbial deprivation, dietary shifts, and psychosocial stress contribute to barrier dysfunction, dysbiosis, and immune dysregulation, favoring Th2 dominance and allergy development. In contrast, exposures that enhance biodiversity, microbial diversity, pollution-free air, and balanced nutrition support active tolerance development, especially via regulatory T cells. Mechanistic insights point to the barrier-microbiota-immune axis as central pathways linking the environment to allergic outcomes. Translational studies, including biodiversity enrichment interventions, maternal and infant dietary strategies, and microbiome-based therapies, illustrate the potential of exposome-informed approaches to allergy prevention. However, major challenges remain in measuring complex exposure mixtures, identifying causal pathways, and integrating exposome data with systems immunology. This review synthesizes current knowledge on how the exposome modulates immune tolerance and outlines future research directions toward precision prevention. A deeper understanding of these interactions is essential to address the rising global allergy burden.
PMID:41076098 | DOI:10.1016/j.imlet.2025.107102
ALTEX. 2025 Oct 10. doi: 10.14573/altex.2506011. Online ahead of print.
ABSTRACT
The European Union's main chemicals regulation, Registration, Evaluation, Authorization and Restriction of Chemicals (REACH), requires chemicals to be evaluated for health and environmental impacts, with animal tests the basis for many evaluations. Most discussions of REACH animal use focus on mammals, yet fish tests are also a significant component. Here we report the animal count for fish tests completed, ongoing, and pending un-der REACH, based directly on test reports. The estimated total to date is 382,000 fish, used for short-term fish toxicity, long-term fish toxicity, endocrine disruption, and bioaccumulation tests. This count does not include new tests that will result from the 2022 REACH amendment, which extends requirements for long-term fish toxicity tests and removes the most common basis for waivers previously accepted for this test. An estimated 940-1,240 new long-term fish toxicity tests may result from these changes, requiring 520,000-680,000 fish. The count also does not include potential expansion of endocrine disruption testing in the upcoming REACH revision. New non-animal alternatives to long-term fish toxicity and endocrine disruption tests are needed to reduce these impacts. For other fish tests, recently defined non-animal methods for short-term toxicity and the newly approved Hyalella azteca Bioconcentration Test for bioaccumulation should be evaluated for inclusion in REACH guidance, both to incentivize their use and to better comply with the REACH mandate to use animal testing only as a last resort.
PMID:41069134 | DOI:10.14573/altex.2506011
Acta Endocrinol (Buchar). 2024 Oct-Dec;20(4):444-454. doi: 10.4183/aeb.2024.444. Epub 2025 Oct 3.
ABSTRACT
OBJECTIVE: Infertility affects an estimated 17.5% of couples worldwide, according to the last report published in 2023 by WHO. A significant cause of this global fertility decline is due to environmental endocrine-disrupting chemicals exposure, which have the ability to interfere with the endocrine system. Bisphenol A (BPA), a synthetic chemical product leads to health concerns for its endocrine-disrupting properties. Jujube honey contains antioxidants and active compounds, has various therapeutic properties. This study aims to determine testicular dysfunction and endocrine imbalance induced by BPA chronic exposure and the possible protective effect of jujube honey in gerbil.
MATERIALS AND METHODS: Eighteen adult male gerbil was either considered as control (n=6, group 1) or exposed to 50 mg BPA/kg/day Group 2, n=6) and the BPA-treated group was given jujube honey at 200 mg/kg/day by oral gavage Group 3, n=6) for six weeks. At the end of the experiment, testicular weight, epididymal sperm count, endocrine status, histopathology of testis tissue and oxidative stress parameters were evaluated.
RESULTS: The results showed a decrease in testicular weight, sperm quality and plasma levels of testosterone and estradiol in the BPA-treated group. Furthermore, histopathological findings revealed germinal epithelium alteration characterized by germ cell degeneration, disordered arrangement of the germ cell layers and vacuolization and decreased number of Ki-67-positive germ cells. The results showed a decrease in testicular levels of superoxide dismutase, catalase and reduced glutathione with an increase of malondialdehyde in the BPA-treated group. However, in the jujube honey+BPA group, histopathological studies revealed a systematic array of germ cells with less vacuolization, improved sperm parameters, restored plasma testosterone and estradiol levels and increased antioxidative capacity of the testes.
CONCLUSION: These findings suggest a potential protective effect of jujube honey against BPA-induced testicular damage and oxidative stress caused by endocrine-disrupting chemicals.
PMID:41069536 | PMC:PMC12506881 | DOI:10.4183/aeb.2024.444
Neuroimmunomodulation. 2025 Oct 8:1-16. doi: 10.1159/000548813. Online ahead of print.
ABSTRACT
Chronic Chagas disease can affect multiple organs, most notably the heart and gastrointestinal tract, and in some cases, the nervous system. However, the underlying pathophysiological mechanisms of this parasitic infection remain incompletely understood. Evidence from studies in both mice with acute Trypanosoma cruzi infection and in patients with Chagas disease has revealed a range of immune-neuroendocrine alterations and metabolic disruptions. In this review, we highlight key findings in human Chagas disease related to these abnormalities and discuss their potential contributions to disease pathogenesis.
PMID:41069094 | DOI:10.1159/000548813
Biol Reprod. 2025 Oct 10:ioaf229. doi: 10.1093/biolre/ioaf229. Online ahead of print.
ABSTRACT
Organophosphate esters (OPEs), widely used as flame retardants and plasticizers, are frequently detected in indoor environments and human tissues, raising concerns about their potential endocrine-disrupting effects. In this study, we examined the effects of a household dust-based mixture of OPEs, along with two structural distinct sub-mixtures, on the phenotype, function, and lipidome on MA10 Leydig cells. Using high-content imaging, we identified increase in oxidative stress levels and accumulation of lipid droplets as common phenotypic effects across mixtures. Notably, the triaryl OPE sub-mixture exhibited greater potency, suggesting that specific structural features contribute to the toxicity of OPEs. While the OPE mixture did not impair basal steroid hormone production in MA-10 cells, changes were observed in stimulated progesterone levels and transcriptional regulation of key steroidogenic transcripts. When comparing lipidomic profiles across three steroidogenic cell lines (MA-10, H295R, and KGN), we found that glycerolipids, particularly triglycerides and diglycerides, consistently appeared to be the most affected lipid species, highlighting a common disruption in the composition of lipid droplet. However, cell line specific effects were also observed, especially in the regulation of cholesterol esters, likely reflecting differences in cholesterol sourcing and steroidogenic pathways. These findings emphasize the importance of evaluating environmentally relevant chemical mixtures and demonstrate that OPEs can disrupt steroidogenic function and lipid metabolism.
PMID:41071121 | DOI:10.1093/biolre/ioaf229
Neurochem Res. 2025 Oct 10;50(5):320. doi: 10.1007/s11064-025-04579-5.
ABSTRACT
Chronic stress disrupts immune-endocrine balance and contributes to major depressive disorder (MDD) through dysregulated autophagy and neuroinflammation pathways, yet their interactions and persistence remain unclear. This study investigated these mechanisms using chronic restraint stress (CRS) in male Wistar rats and in silico MDD gene analysis. Rats were exposed to CRS for 15 days (Res15) or 30 days (Res30), followed by a 30-day stress-free recovery period without intervention (Res30/Rec30). Behavioral assessments (anxiety, depression-like behaviors, and cognition) were conducted via standard tests. Blood samples were analyzed for neutrophil-to-lymphocyte ratio (NLR) and corticosterone levels. Hippocampal cytokine expression (TNF-α, IL-1β, IL-16), Beclin1 levels, and neuronal damage were evaluated via molecular and histopathological methods. In silico analysis linked these pathways to human MDD by identifying upregulated autophagy- and inflammation-related genes (including IL1B, PTGS2, GNAI3, RAB1A, MAP1LC3B, SQSTM1, and KIF5B), bridging rodent stress models to clinical depression. CRS induced anxiety- and depression-like behaviors, cognitive impairment, hippocampal neurodegeneration, elevated corticosterone and NLR, and upregulation of pro-inflammatory and autophagy markers. Although partial recovery in depression-like behaviors and cytokine levels was observed after 30 days, anxiety-like behaviors, cognitive impairment, elevated NLR, and hippocampal neurodegeneration persisted. These findings reveal persistent neurobiological consequences of chronic stress, advancing understanding of MDD pathophysiology and suggesting that targeting autophagy and neuroinflammation could offer novel treatments for depression, particularly for symptoms that endure post-stress.
PMID:41071241 | DOI:10.1007/s11064-025-04579-5
Sci Total Environ. 2025 Oct 9;1003:180680. doi: 10.1016/j.scitotenv.2025.180680. Online ahead of print.
ABSTRACT
Endocrine disrupting chemicals (EDCs) that interfere with estrogenic, androgenic, thyroidal and steroidogenic (EATS) pathways, as well as non-EATS pathways, should be identified and classified under EU chemical regulations. Identifying and classifying obesogenic EDCs is particularly challenging, as they are typically regulated through non-EATS mechanisms and lack standardized test methods and guidance for evaluation. This review evaluates fish models of obesity, synthesizes current evidence on chemical effects on fish adipogenesis, and discusses the regulatory challenges associated with EDC identification and classification. Diet-induced obesity (DIO) fish models have been developed in species such as zebrafish, medaka, tilapia, rainbow trout, and others. However, the composition and quantity of diets in these studies vary significantly. Notably, the high calorie diet used to induce obesity in one zebrafish experiment may be equivalent to the control diet in another. Fat accumulation in fish has been studied in pharmaceuticals, bioactive chemicals, biocides, pesticides, and industrial chemicals. Body weight, body mass index (BMI), condition factor, and various endpoints derived from adipose tissue are commonly used to investigate obesity-related effects in fish. However, body weight alone may not reliably indicate adiposity. Obesity in fish is not explicitly addressed in existing OECD test guidelines. A mode of action (MOA) analysis is needed to identify and classify obesogenic EDCs. Both EATS and non-EATS pathways should be evaluated to establish biological plausibility regarding effects on population relevant obesogenic endpoints in fish. The challenges of using fish models of obesity are discussed, along with recommendations for incorporating relevant obesity related endpoints into test guidelines.
PMID:41072194 | DOI:10.1016/j.scitotenv.2025.180680
Anal Chim Acta. 2025 Nov 22;1376:344612. doi: 10.1016/j.aca.2025.344612. Epub 2025 Sep 4.
ABSTRACT
BACKGROUND: Bisphenol analogues (BPs) are recognized as endocrine disrupting chemicals (EDCs) that pose risks to human health. However, the accurate detection of BPs faces significant challenges due to their trace-level concentrations and matrix interference in environmental and food samples. Therefore, efficient enrichment procedures are usually required prior to instrumental analysis. For this reason, the development of novel functional materials capable of simultaneously enriching and rapidly capturing multiple BPs holds significant research importance.
RESULTS: In this study, a novel metalloporphyrin-based porous polymer was synthesized using 2,5-divinylterephthalaldehyde (Dva) and 5,10,15,20-Tetrakis-(4-aminophenyl)-porphyrin-Cu-(II) (CuTAPP). Adsorption performance tests demonstrated that CuTAPP-Dva exhibited remarkable adsorption capacity for three typical BPs, with saturated adsorption capacities of 343.96, 295.71, and 270.35 mg/g for bisphenol A (BPA), bisphenol F (BPF), and bisphenol S (BPS), respectively. Comprehensive characterization techniques revealed that the adsorption mechanism involves pore filling, π-π stacking interactions, and hydrogen bond. Benefiting from its excellent adsorption performance, CuTAPP-Dva was successfully developed as an efficient solid-phase extraction adsorbent. Milk, tea beverage, and fruit juice were pre-treated through operations such as centrifugation and filtration to obtain food extracts. Combined with HPLC-DAD, this method can be used for the analysis of food extracts, successfully achieving the enrichment and detection of BPs in milk, tea beverage, and fruit juice. Wide linear ranges were obtained, with LODs of 0.07-0.62 μg/L and LOQs of 0.20-1.88 μg/L. In spiked real samples, recoveries were≥ 82.66 %.
SIGNIFICANCE: This study successfully developed a novel functional material, achieving efficient enrichment and rapid capture of BPA, BPF, and BPS, demonstrating that porphyrin-based polymers with π-π conjugated structures possess the ability for synergistic adsorption of multiple BPs. This achievement not only provides an innovative material for the enrichment and monitoring of BPs, but also offers novel ideas and methods for the enrichment of other trace pollutants.
PMID:41073007 | DOI:10.1016/j.aca.2025.344612
Biol Trace Elem Res. 2025 Oct 11. doi: 10.1007/s12011-025-04840-6. Online ahead of print.
ABSTRACT
Fluoride exposure via contaminated drinking water is a significant global public health concern. Fluoride being beneficial at minimal concentrations was used for dental caries prevention, but excessive exposure of fluoride has been associated with numerous health disorders including skeletal and dental fluorosis, weakening of bones making them more prone to fractures, impaired intelligence, stunted growth, reduced birth and fertility rates, and disruption of thyroid function. This review provides a concise overview of all the existing literature on the effects of fluoride on the thyroid gland till date. Various data collection methods including PubMed, Scopus, ResearchGate, and Google Scholar were used to collect relevant research papers using keywords "changes caused by fluoride in thyroid" or "fluoride induced toxicity on the thyroid gland" ranging from 1976 till date. Fluoride adversely affects thyroid function via interfering with iodine metabolism (replacing iodine in the gland and also inhibiting its uptake). It also disrupts T3 and T4 production causing decrease in their levels, increased TSH, oxidative stress, and downregulated antioxidant and thyroid-related genes. Histopathological alterations caused by fluoride includes thyroid follicular cell apoptosis, necrosis, and hyperplasia of thyroid gland. Thyroid gland, in particular, is highly susceptible to fluoride accumulation, making it one of the most affected organs. Numerous studies have evaluated the impact of fluoride on mammalian models, with a focus on endocrine system particularly the thyroid gland. Fluoride exposure can lead to hypothyroidism, particularly detrimental during fetal and early developmental stages affecting IQ, brain, and hearing development.
PMID:41073679 | DOI:10.1007/s12011-025-04840-6
Environ Toxicol. 2025 Oct 10. doi: 10.1002/tox.24574. Online ahead of print.
ABSTRACT
Benzo[a]pyrene (BaP) is an environmental polycyclic aromatic hydrocarbon known to act as an endocrine disruptor. Cardamom (Elettaria cardamomum) is a widely used spice with strong biological and antioxidant properties. The current work aimed to clarify the mechanism of action of cardamom essential oil (CEO) and explore its phytochemical components and protective benefits to reduce testicular damage caused by BaP. GC-MS analysis revealed that the CEO had several potent antioxidant and radical scavenging components. Male Wistar Dawley rats were classified into 4 groups (7 rats/group): negative control, CEO (100 mg/kg bw), positive control (BaP; 5 mg/kg bw), and CEO plus BaP, respectively. Rats were administered daily oral doses for 4 weeks. Rats exposed to BaP exhibited significant (p < 0.05) increases in testicular TBARS, serum aminotransferases, and acid phosphatase. This was accompanied by a decrease in body weight, reduced glutathione, antioxidant enzymes, and hydroxysteroid dehydrogenase activities. Moreover, significant (p < 0.05) changes were observed in gene expression (Bax, Cas-3, Bcl-2, and Beclin-1), hormone levels (Testosterone, FSH, and LH), sperm quality, and histological structure. However, CEO pretreatment to BaP-intoxicated rats demonstrated a significant (p < 0.05) improvement in most indices compared to the BaP-exposed group. Conclusively, phenolic and flavonoid components of CEO demonstrated a potent antioxidant activity against BaP toxicity.
PMID:41070933 | DOI:10.1002/tox.24574
Environ Res. 2025 Oct 9;287:123037. doi: 10.1016/j.envres.2025.123037. Online ahead of print.
ABSTRACT
Per- and polyfluoroalkyl substances (PFAS) are persistent endocrine-disrupting chemicals (EDCs) linked to adverse reproductive outcomes. While the placenta is a known target of PFAS toxicity, most in vitro studies use two-dimensional (2D) cell culture models, often focusing on late-pregnancy tissue or blood PFAS concentrations and examining single compound exposures. In this study, we measure placenta PFAS concentrations in early pregnancy and design a placenta-relevant PFAS mixture to assess its impact on trophoblast function using a three-dimensional (3D) trophoblast spheroid model. PFAS levels in first-trimester placental tissue were quantified using liquid chromatography/triple quadrupole mass spectrometry. Six PFAS: perfluorononanoic acid (PFNA), perfluorooctanesulfonic acid (PFOS), perfluorobutanoic acid (PFBA), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), and perfluorodecanoic acid (PFDA); were selected based on their placenta concentrations and relevance to pregnancy complications to design the placenta real-life PFAS mixture. Next, trophoblast spheroids were propagated from two different cell lines, JEG-3 and HTR-8/SVneo, to assess the effects of PFAS mixture on trophoblast viability, apoptosis, invasion, hormone production, and gene expression. While trophoblast spheroid viability remained largely unaffected, we observed changes in trophoblast function. PFAS exposure significantly increased invasiveness in JEG-3 spheroids at 48 h, but markedly reduced it in HTR-8/SVneo spheroids at 96 h across varying concentrations. Additionally, pregnancy-specific hormone e.g. β-hCG production declined after 48 h of PFAS mixture exposure in JEG-3 spheroids. Gene expression analysis revealed altered apoptosis and proliferation pathways in both trophoblast spheroids. Overall, our study highlights that physiologically relevant 3D trophoblast models can contribute to the broader comprehension of PFAS-associated reproductive health risk assessments.
PMID:41067679 | DOI:10.1016/j.envres.2025.123037
Mar Pollut Bull. 2025 Oct 8;222(Pt 2):118794. doi: 10.1016/j.marpolbul.2025.118794. Online ahead of print.
ABSTRACT
Phenol derivatives such as bisphenol A (BPA), 4-tert-octylphenol (4-t-OP), and 4-nonylphenol (4-NP) are endocrine-disrupting compounds (EDCs) that enter the marine food web and are transported over long distances due to their affinity for organic matter. This study examined their occurrence and bioaccumulation in macrozoobenthic organisms from four Arctic fjords in Spitsbergen (Kongsfjorden, Hornsund, Adventfjorden, Isfjorden), considering spatial distribution, environmental conditions, and feeding strategies. Benthic invertebrates are exposed to EDCs through ingestion of suspended and resuspended organic matter and serve as prey for higher trophic levels, potentially facilitating contaminant transfer to fish, birds, and marine mammals. The highest 4-NP levels were found in Kongsfjorden, while BPA peaked in Hornsund. Filter feeders and deposit feeders exhibited the highest accumulation, indicating feeding mode as a key factor. EDC presence correlated with human activities (sewage, tourism) and long-range transport via ocean currents. Our findings confirm the widespread occurrence of phenol derivatives even in remote Arctic environments, highlighting their persistence and ecological risk. These results underscore the urgent need to reduce pollutant emissions, control long-range transport, and implement protective measures for vulnerable Arctic ecosystems.
PMID:41066842 | DOI:10.1016/j.marpolbul.2025.118794
Environ Toxicol Pharmacol. 2025 Oct 9;120:104842. doi: 10.1016/j.etap.2025.104842. Online ahead of print.
ABSTRACT
Polycystic ovary syndrome (PCOS) is an endocrine condition affecting women of reproductive age, characterized by hyperandrogenism, ovulatory dysfunction, and some metabolic disturbances. Emerging evidence has been suggesting a link between certain endocrine-disrupting chemicals (EDCs), such as bisphenol A (BPA) and phthalates, and the pathogenesis and/or exacerbation of PCOS. These exogenous compounds interfere with hormonal function, potentially inducing epigenetic modifications and disrupting insulin sensitivity, primarily when exposure occurs during specific periods. This review explores the role of EDCs in the onset and progression of the condition, and it also outlines current therapeutic strategies, including hormonal contraceptives, insulin sensitizers, ovulation induction agents, and anti-androgenic treatments. Novel approaches targeting gut microbiota, cytokine modulation, and antioxidant therapies are discussed, alongside preventive measures to reduce EDC exposure. Thus, this review highlights the need for a personalized, multimodal management of PCOS, integrating pharmacological, lifestyle, and behavioural intervention. Nevertheless, for some of these therapies, it also emphasizes some lack of causality, as well as limited clinical trial data to support their efficacy.
PMID:41067401 | DOI:10.1016/j.etap.2025.104842
Toxicology. 2025 Oct 7:154300. doi: 10.1016/j.tox.2025.154300. Online ahead of print.
ABSTRACT
Metabolism disrupting chemicals (MDCs) are a class of endocrine disrupting substances that promote metabolic changes leading to metabolic disorders in humans. Central to assessing their adverse effects is the need to better understand their modes of action (MoA). Cytochrome P450 (CYP) enzymes play a major role in xenobiotic metabolism, but also catalyse many endogenous metabolic reactions. Therefore, modulation of CYP functionality may impact homeostasis, contributing to adverse outcomes. At the functional level, alteration of the activity of human CYPs by MDCs largely remains unexplored. In this study we investigated the capability of six candidate MDCs, bisphenol A (BPA), perfluorooctanoic acid (PFOA), tributyltin (TBT), dichlorodiphenyldichloroethylene (p,p'-DDE), triclosan (TCS) and triphenylphosphate (TPP) to induce CYP1A2, CYP2B6 and CYP3A4 activities in the human hepatic HepaRG cell line. The CYP induction test method previously validated for pharmaceuticals was optimised and selected MDCs were tested in the context of the European Horizon 2020 GOLIATH project. Induction was revealed using a cocktail of CYP-selective probe substrates, followed by probe metabolite quantification by mass spectrometry. All MDCs except TCS induced CYP activities. PFOA, TBT, p,p'-DDE and TPP induced CYP1A2, TPP being the most potent inducer. BPA, PFOA, TBT and TPP induced CYP2B6, PFOA being the most potent inducer. BPA, PFOA, TBT, p,p'-DDE and TPP all induced CYP3A4, p,p'-DDE and BPA being the most potent inducers. These results highlight the capability of candidate MDCs to induce key CYP activities in a human hepatic relevant model, paving the way for a better understanding of MDCs mechanisms of action.
PMID:41067530 | DOI:10.1016/j.tox.2025.154300
Environ Res. 2025 Oct 9;287:123037. doi: 10.1016/j.envres.2025.123037. Online ahead of print.
ABSTRACT
Per- and polyfluoroalkyl substances (PFAS) are persistent endocrine-disrupting chemicals (EDCs) linked to adverse reproductive outcomes. While the placenta is a known target of PFAS toxicity, most in vitro studies use two-dimensional (2D) cell culture models, often focusing on late-pregnancy tissue or blood PFAS concentrations and examining single compound exposures. In this study, we measure placenta PFAS concentrations in early pregnancy and design a placenta-relevant PFAS mixture to assess its impact on trophoblast function using a three-dimensional (3D) trophoblast spheroid model. PFAS levels in first-trimester placental tissue were quantified using liquid chromatography/triple quadrupole mass spectrometry. Six PFAS: perfluorononanoic acid (PFNA), perfluorooctanesulfonic acid (PFOS), perfluorobutanoic acid (PFBA), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), and perfluorodecanoic acid (PFDA); were selected based on their placenta concentrations and relevance to pregnancy complications to design the placenta real-life PFAS mixture. Next, trophoblast spheroids were propagated from two different cell lines, JEG-3 and HTR-8/SVneo, to assess the effects of PFAS mixture on trophoblast viability, apoptosis, invasion, hormone production, and gene expression. While trophoblast spheroid viability remained largely unaffected, we observed changes in trophoblast function. PFAS exposure significantly increased invasiveness in JEG-3 spheroids at 48 h, but markedly reduced it in HTR-8/SVneo spheroids at 96 h across varying concentrations. Additionally, pregnancy-specific hormone e.g. β-hCG production declined after 48 h of PFAS mixture exposure in JEG-3 spheroids. Gene expression analysis revealed altered apoptosis and proliferation pathways in both trophoblast spheroids. Overall, our study highlights that physiologically relevant 3D trophoblast models can contribute to the broader comprehension of PFAS-associated reproductive health risk assessments.
PMID:41067679 | DOI:10.1016/j.envres.2025.123037
Brief Bioinform. 2025 Aug 31;26(5):bbaf531. doi: 10.1093/bib/bbaf531.
ABSTRACT
Type 2 diabetes (T2D) is a complex metabolic disorder strongly influenced by genetics. Most genetic studies, including expression quantitative trait loci (eQTL) analyses, use bulk pancreatic tissue, masking cell-specific mechanisms. Here, by integrating single-cell RNA sequencing, chromatin accessibility, and genome-wide association studies (GWAS) data, we systematically identified 328 pancreatic cell-type-specific cis-eQTLs associated with T2D. We pinpointed nine key genes (including STIL in beta and delta cells; ZSWIM5 in alpha, delta, and ductal cells; IL1RN, ANP32E, IPP, MLLT11, and SLC23A3 in delta cells; SNX4 in gamma cells; and RBMS1 in beta cells) whose SNPs overlapped with chromatin accessibility peaks. These genes highlight regulatory pathways in beta-cell dysfunction, metabolic stress responses, and disrupted pancreatic homeostasis. A public database, CTPeQTLs (https://ctpeqtls.netlify.app/), was developed to explore cis-eQTLs across diabetic and non-diabetic cohorts, revealing distinct regulatory patterns in both endocrine and exocrine cells, as well as disease-associated transcriptional dysregulation. Our findings uncover cell-specific genetic mechanisms in diabetes and provide potential therapeutic targets, supporting precision medicine strategies.
PMID:41066696 | PMC:PMC12510404 | DOI:10.1093/bib/bbaf531
Cureus. 2025 Sep 7;17(9):e91784. doi: 10.7759/cureus.91784. eCollection 2025 Sep.
ABSTRACT
While typically viewed as indolent, papillary thyroid carcinoma (PTC) is a clinically significant health condition, especially among women, as the primary treatment for PTC, thyroidectomy, and disproportionately affects them. Thyroidectomy disrupts endocrine function, often necessitating a lifetime of hormone replacement therapy, yet postoperative hormonal outcomes remain understudied. PTC's global research trends, post-treatment effects, and treatment methods are the primary focus of this bibliometric analysis, as the growing awareness of PTC and medical drug toxicity continues to stimulate medical research. Bibliometric methods were used to evaluate trends in PTC-related publications from 2016 to 2025, acquiring data from the Web of Science database. The database searched for the following keywords: "papillary thyroid carcinoma", "thyroidectomy", "hormone replacement therapy", and "women's health." Data were downloaded and analyzed using VOSviewer (Leiden University, Leiden, The Netherlands), a bibliometric network creation and visualization software. The qualitative analysis included analysis of co-occurrence of specific keywords in and between publications, common co-authorships, analysis of national collaboration networks, and thematic mapping. Results indicated that the literature primarily focuses on PTC and surgical treatments while neglecting endocrine outcomes, hormonal challenges, and postoperative quality of life. The keywords "surgery" and "management" are widespread, whereas "levothyroxine" and "replacement therapy" are rarely used. Despite the thyroid gland's central position in endocrine control, few studies connect treatment of PTC with any systemic hormonal effects. Moreover, international collaboration is highest between France, the People's Republic of China, and the United States, with the same nations also topping PTC publication figures. A growing interest is shown by the increasing number of publications. Throughout, the bibliometric analysis finds both a notable scarcity of literature on hormonal outcomes in female patients with PTC who have been treated with thyroidectomy and an abundance of surgical literature on common treatment methods for PTC. Unlike existing bibliometric studies, this paper centers on gender-specific consequences and underrepresented endocrine outcomes, offering new insights into long-neglected dimensions of PTC care.
PMID:41063907 | PMC:PMC12503003 | DOI:10.7759/cureus.91784
J Assist Reprod Genet. 2025 Oct 9. doi: 10.1007/s10815-025-03678-0. Online ahead of print.
ABSTRACT
Environmental changes are a growing global concern, and their impact on reproductive health remains incompletely understood. In this narrative review, conducted on behalf of the Italian Society of Fertility and Sterility and Reproductive Medicine (SIFES-MR), we examined the impact of the environment on male fertility, considering endocrine-disrupting chemicals (EDCs), air pollution, and global warming, with the aim of identifying strategies to improve reproductive outcomes. Scientific literature demonstrates that all these aspects may contribute to a decline in reproductive health, impairing sperm count, motility, and morphology as well as reducing testicular hormonal function. Future research should focus on the role of environmental factors in male hypogonadism, impaired spermatogenesis, genital abnormalities, and transgenerational effects.
PMID:41068550 | DOI:10.1007/s10815-025-03678-0
Mikrochim Acta. 2025 Oct 10;192(11):721. doi: 10.1007/s00604-025-07577-0.
ABSTRACT
A modified screen-printed carbon electrode (SPCE) has been developed for the determination of bisphenol A (BPA), a compound widely used in plastics and resins production, which can disrupt endocrine and reproductive human systems. Magnetic graphene oxide (MGO) was synthesized following a sustainable protocol based on mechanochemistry. Then, MGO was combined with a molecularly imprinted pyrrole-based polymer (MIPPy) for the preparation of a novel magnetic nanocomposite (BPA@MIPPy), characterized by several imaging, spectroscopic, and electrochemical techniques. The magnetic properties of BPA@MIPPy allowed the manipulation of the material, including separation, analyte preconcentration, and electrode modification. Differential pulse voltammetry (DVP) was the selected electrochemical technique for BPA detection, presenting high sensitivity (LOD = 29 nM, LOQ = 97 nM) and precision under optimum conditions. To study selectivity, the response of the sensor toward four potential interferents was evaluated (phenol, methanol, sodium nitrate, and ascorbic acid), and no interference was observed. Finally, a real wastewater sample was successfully analyzed, demonstrating that the method is adequate for water-control applications.
PMID:41068448 | DOI:10.1007/s00604-025-07577-0
Front Endocrinol (Lausanne). 2025 Sep 22;16:1638655. doi: 10.3389/fendo.2025.1638655. eCollection 2025.
ABSTRACT
BACKGROUND: Gestational Diabetes Mellitus (GDM) is a transient diabetogenic state that often leads to adverse maternal and fetal outcomes. The rising burden of exposure to endocrine-disrupting chemicals like phthalates essentially disrupts the tightly regulated endocrine system, thereby modulating the insulin signaling pathways, leading to GDM.
OBJECTIVE: In the present work, a systematic review was performed to examine the probable relation between maternal exposure to phthalates, as endocrine-disrupting compounds, and GDM.
METHODS: Relevant studies from their inception to April 2025 were identified by searching PubMed, Embase, Scopus, and Science Direct. The data were screened using the Rayyan tool, and the risk of bias was assessed using the New Castle Ottawa Scale selection tool.
RESULTS: We identified 13 studies that showed a significant presence of phthalates in the urine samples of GDM patients. 5 phthalate secondary metabolites, Monoethyl Phthalate, Monobutyl phthalate, Mono-Isobutyl Phthalate, and Monobenzyl Phthalate and the primary phthalate Di(2-ethylhexyl) Phthalate were found to be most commonly present in the urine samples of the GDM patients.
CONCLUSION: Urinary phthalate levels can be used as a non-invasive biomarker for GDM, thereby also reducing the risk of associated adverse pregnancy outcomes.
SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD420251023656.
PMID:41059223 | PMC:PMC12497590 | DOI:10.3389/fendo.2025.1638655
Sci Rep. 2025 Oct 8;15(1):35128. doi: 10.1038/s41598-025-19064-w.
ABSTRACT
Plastics pose a significant global threat to the ecosystems due to their accumulation and impact on human health. The degradation of plastics results in the formation of microplastics (MPs), small particles less than 5 mm in size, which are released into the environment. Polystyrene (PS) is a major chemical component of plastics, and exposure to PS-based microplastics (PS-MPs) has been linked to cellular damage. This study aimed to explore the effects of 1 μm PS-MPs on human gingival fibroblast cells (hGF). PS-MPs induced a limited cytotoxicity at the tested concentrations and time points. Confocal microscopy, TEM and flow cytometry revealed the uptake of PS-MPs in about 10% of hGF cells. Proteomics identified a profoundly altered proteostasis in PS-MPs treated cells. Enrichment analysis of differentially expressed proteins uncovered disruptions in cellular pathways, including metabolisms (glycolysis and adipogenesis), endocrine functions (androgen and oestrogen responses), inflammatory responses (interferons α and γ) and cancer progression (epithelial-mesenchymal transition). Consistent with the enrichment analysis, treated cells exhibited a significant increase in motility. This study demonstrated that PS-MPs are internalized by cells and influence key cellular pathways related to inflammation, motility, and survival, reinforcing the notion that PS-MP exposure may pose risks to human health.
PMID:41062560 | PMC:PMC12508049 | DOI:10.1038/s41598-025-19064-w
Hear Res. 2025 Oct 2;467:109442. doi: 10.1016/j.heares.2025.109442. Online ahead of print.
ABSTRACT
Polychlorinated biphenyls (PCBs), a class of persistent endocrine-disrupting chemicals, continue to pose significant risks to human and environmental health due to their widespread distribution, lipophilicity, and ability to bioaccumulate. Of particular concern is exposure during critical periods of neurodevelopment, which has been associated with long-lasting effects on sensory systems, including auditory processing. This review elaborates findings from both human epidemiological studies and animal models to examine the effects of PCBs on auditory function across the peripheral and central auditory pathways. Evidence indicates that PCB exposure during gestation and early postnatal life can lead to permanent auditory deficits. At the level of the auditory periphery, reductions in distortion-product otoacoustic emissions (DPOAEs) and auditory brainstem responses (ABRs) suggest cochlear outer hair cell dysfunction, potentially mediated by oxidative stress. Centrally, alterations in the primary auditory cortex and inferior colliculus have been observed, including disrupted tonotopic organization, excitation-inhibition imbalance, and impaired neuroplasticity. Notably, such central neural changes can occur out of proportion to abnormalities in ABRs, pointing to central auditory vulnerabilities. Epidemiological data in humans further support these findings, with certain PCB congeners linked to a significantly elevated risk of hearing impairment in children. PCB exposure coupled with loud noise exposure, which is growing in prevalence, leads to cumulative deficits in auditory processing. Together, these findings highlight the multi-level impact of PCB exposure on the auditory system and highlight the need for further investigation into the molecular and circuit-level mechanisms underlying these effects. Understanding the actions of PCB congeners on the auditory system in various human population cohorts is important to inform risk assessment and guide future public health policies.
PMID:41061429 | DOI:10.1016/j.heares.2025.109442
Ecotoxicol Environ Saf. 2025 Oct 7;305:119174. doi: 10.1016/j.ecoenv.2025.119174. Online ahead of print.
ABSTRACT
Parabens are widely used as antimicrobial preservatives in cosmetics, personal care products, and pharmaceuticals. However, their endocrine-disrupting potential, particularly their impact on 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), remains unclear. This study evaluated 9 parabens for their inhibitory potency against human placental and rat renal 11β-HSD2, mode of action, structure-activity relationship (SAR), molecular interactions (via in silico docking) and surface plasmon resonance (SPR) binding analysis, and effects on HSD11B2 expression and cortisol metabolism in human placental BeWo cells. Nonyl paraben was the most potent inhibitor in both species, with the lowest IC50 (human: 15.24 μM, rat: 10.79 μM) and strongest binding affinity (KD: human 3.38 × 10-5 M; ΔG: human: -6.43 kcal/mol, rat: -6.37 kcal/mol). Short-chain parabens (<C4) and paraben acid showed no inhibition at 100 μM, suggesting chain length-dependent activity. All active parabens exhibited mixed inhibition, binding both the free enzyme and the enzyme-substrate complex. These parabens also inhibited cortisol metabolism in intact BeWo cells at or below 100 μΜ and both heptyl and nonyl parabens downregulated HSD11B2 expression. Molecular docking revealed that nonyl paraben interacts with the NAD+ cofactor site in humans and rats. SAR analysis identified lipophilicity and molecular weight as key determinants of inhibitory strength, with higher values correlating with greater potency. A 3D-QSAR pharmacophore model confirmed hydrophobic interactions as essential for inhibition. Species-specific differences in binding mechanisms highlight the need for caution when extrapolating animal data to humans. These results provide critical insights into the endocrine-disrupting effects of parabens, emphasizing their potential to interfere with cortisol homeostasis in a structure and species-dependent manner.
PMID:41061448 | DOI:10.1016/j.ecoenv.2025.119174
Environ Int. 2025 Oct 4;204:109829. doi: 10.1016/j.envint.2025.109829. Online ahead of print.
ABSTRACT
Childhood obstructive sleep apnea (OSA) is a common pediatric sleep disorder characterized by recurrent sleep-related upper airway dysfunction. China has the highest number of OSA sufferers (176 million) globally. Environmental endocrine-disrupting chemicals (EDCs) posed unrecognized threats to pediatric OSA are not clear. We examined the associations of 34 kinds of EDCs with childhood OSA in Southern China. We recruited 334 children aged ≤ 15 years (July-September 2022) from a tertiary sleep clinic in Shenzhen. Using HPLC-MS/MS, we quantified 7 organophosphate flame retardants (OPFRs), 3 parabens, 10 phthalate metabolites (PAEs), 4 benzophenones (BPs), 7 synthetic phenolic antioxidants (SPAs), and 3 bisphenols. Multivariable linear regression evaluated single-chemical associations with polysomnography-derived indices: apnea-hypopnea index (AHI), obstructive AHI (OAHI), oxygen desaturation index (ODI), and blood oxygen saturation (SpO2) levels. Mixture effects were assessed through quantile-based g-computation (Qgcomp). Multiple EDCs demonstrated significant dose-response relationships with AHI, OAHI, and ODI (p < 0.05), while inversely associated with SpO2. Qgcomp revealed each tertile increase in EDC mixture concentration corresponded to elevated AHI [18.53 % (95 % CI: 6.18 to 32.31)], OAHI [23.27 % (13.88 to 34.99)], and ODI [15.03 % (5.13 to 24.61)], along with decreased baseline SpO2 [-0.25 (-0.49 to -0.01)], lowest SpO2 [-1.09 (-2.17 to -0.01)], and mean SpO2 [-0.39 (-0.70 to -0.07)], with DBP exhibiting the strongest negative effects on AHI, OAHI, and ODI, and BCIPP showing the greatest positive effects on baseline and mean SpO2. This first biomonitoring study implicates EDC mixtures, particularly phthalates and OPFRs, in pediatric OSA pathogenesis. Our findings underscore the need for chemical policy reforms and longitudinal investigations elucidating biological mechanisms linking environmental exposures to sleep-disordered breathing.
PMID:41061494 | DOI:10.1016/j.envint.2025.109829
Sci Rep. 2025 Oct 8;15(1):35128. doi: 10.1038/s41598-025-19064-w.
ABSTRACT
Plastics pose a significant global threat to the ecosystems due to their accumulation and impact on human health. The degradation of plastics results in the formation of microplastics (MPs), small particles less than 5 mm in size, which are released into the environment. Polystyrene (PS) is a major chemical component of plastics, and exposure to PS-based microplastics (PS-MPs) has been linked to cellular damage. This study aimed to explore the effects of 1 μm PS-MPs on human gingival fibroblast cells (hGF). PS-MPs induced a limited cytotoxicity at the tested concentrations and time points. Confocal microscopy, TEM and flow cytometry revealed the uptake of PS-MPs in about 10% of hGF cells. Proteomics identified a profoundly altered proteostasis in PS-MPs treated cells. Enrichment analysis of differentially expressed proteins uncovered disruptions in cellular pathways, including metabolisms (glycolysis and adipogenesis), endocrine functions (androgen and oestrogen responses), inflammatory responses (interferons α and γ) and cancer progression (epithelial-mesenchymal transition). Consistent with the enrichment analysis, treated cells exhibited a significant increase in motility. This study demonstrated that PS-MPs are internalized by cells and influence key cellular pathways related to inflammation, motility, and survival, reinforcing the notion that PS-MP exposure may pose risks to human health.
PMID:41062560 | PMC:PMC12508049 | DOI:10.1038/s41598-025-19064-w
Sci Rep. 2025 Oct 8;15(1):35054. doi: 10.1038/s41598-025-20174-8.
ABSTRACT
This study investigates the mechanisms by which environmental factors affect ovarian function. Environmental toxins and unhealthy lifestyles adversely affect women's health, primarily impair ovarian function. Environmental toxins and unhealthy lifestyles can negatively impact women's health, particularly by impairing ovarian function. Streptozotocin (STZ), dehydroepiandrosterone (DHEA) and letrozole (LET) with high-fat diet (HFD) (only LET was combined with HFD), induced models have been experimentally demonstrated to induce ovarian dysfunction. This investigation aims to elucidate their individual and synergistic effects on ovarian function to inform evidence-based prevention and intervention strategies for ovarian dysfunction. ICR/JCL mice (age 4-5 weeks) were subjected to three distinct pathophysiological modeling approaches to simulate ovarian dysfunction. Multiparametric analysis systematically evaluated physiological changes, glycometabolism function, endocrine parameters, and molecular biology. Experimental outcomes demonstrated that STZ, DHEA and LET with HFD significantly affected mice's metabolic and ovarian functions. Mechanistically, the PI3K/AKT signaling pathway was identified as a critical mediator of ovarian dysfunction. In conclusion, this study systematically compared, for the first time, the individual and synergistic effects of STZ, DHEA and LET with HFD on ovarian function in mice, confirming that these environmental factors induce ovarian dysfunction through metabolic disruption and signal transduction pathway dysregulation. Future research should prioritize elucidating the specific molecular mechanisms by which environmental factors impair ovarian function to establish a scientific foundation for developing targeted intervention strategies.
PMID:41062642 | PMC:PMC12508425 | DOI:10.1038/s41598-025-20174-8
Chemistry. 2025 Oct 8:e01905. doi: 10.1002/chem.202501905. Online ahead of print.
ABSTRACT
Esterases play a crucial role in the degradation of phthalic acid esters (PAEs), the common persistent organic pollutants and endocrine disrupting chemicals. However, only a few esterases for PAEs degradation have been characterized. In this study, a novel esterase from Desulfurellaceae bacterium (DeEst) has been identified. We found its hydrolytic activity toward three regioisomers of benzene-dicarboxylic acid esters (i.e., diethyl phthalate, diethyl isophthalate, and diethyl terephthalate). Notably, DeEst is capable of hydrolyzing diethyl phthalate and other PAEs to phthalic acid (PA). The biochemical characterization of DeEst was also investigated. DeEst exhibited strong thermal stability and demonstrated an uncommon thermal activation effect, highlighting its considerable potential for practical applications.
PMID:41058265 | DOI:10.1002/chem.202501905
J Hazard Mater. 2025 Oct 4;499:140051. doi: 10.1016/j.jhazmat.2025.140051. Online ahead of print.
ABSTRACT
The Arctic cryosphere, recognised as a reservoir for pollutants, faces the risk of becoming a secondary source of pollution due to climate-driven thawing and glacial melt. This study presents new data on concentrations and deposition fluxes of contaminants of emerging Arctic concern, specifically phenolic endocrine-disrupting compounds (PEDCs, e.g. bisphenol A and nonylphenols) and 17 pharmaceuticals and personal care products (PPCPs, including antibiotics, analgesics, hormones, and insect repellents). The samples were collected from snow and shallow ice cores from three glaciers in Svalbard during 2022-2023. Contaminants were consistently detected across all sites, with PPCPs dominating in 2023. Concentrations reached up to 211.6 ng/L for PEDCs and 106.3 ng/L for PPCPs, significantly exceeding levels previously reported for POPs. Spatial patterns indicate that local emissions and long-range atmospheric transport drive contaminant distribution. Deposition fluxes revealed the influence of snow density, altitude, and physicochemical properties of compounds on modulating contaminant accumulation. Snow and ice release contaminants annually, driven by the interaction of atmospheric deposition, interannual climate variability, and physical snow/ice changes. These findings underscore the rising environmental relevance of emerging pollutants in polar regions and the ecological risks posed by their remobilisation due to cryosphere melt.
PMID:41061542 | DOI:10.1016/j.jhazmat.2025.140051
Endocrinology. 2025 Oct 7:bqaf146. doi: 10.1210/endocr/bqaf146. Online ahead of print.
ABSTRACT
Endometriosis is a pathological condition characterized by the ectopic growth of endometrial cells, leading to chronic pelvic pain and infertility. Epidemiological studies have associated exposure to dioxin-like polychlorinated biphenyls (PCBs), particularly PCB126, with an increased risk of endometriosis. However, the underlying mechanisms of this association remain poorly understood. We utilized a surgically induced endometriosis mouse model and human endometrial cell lines to assess the impact of PCB126 on endometriosis progression. Mice were exposed to environmentally relevant doses of PCB126. Endometriotic lesion growth, estrogen receptor signaling, receptor tyrosine kinase activity, and gene expression changes induced by PCB126-mediated elevation of DNA methyltransferase 3A (DNMT3A) were evaluated using histology, bioluminescent imaging, immunoblotting, and RNA sequencing. Functional validation was conducted using a pharmacologic AXL inhibitor and tissue-specific Dnmt3a knockout mice. PCB-126 significantly promoted the growth of ectopic lesions and humanized models of endometriosis. Mechanistically, PCB-126 enhanced estrogen receptor beta (ESR2) activity by upregulating AXL and its ligand, Growth Arrest-Specific 6 (GAS6), and elevating DNMT3A expression. The inhibition of AXL signaling suppressed the growth of endometriotic lesions. ESR2 directly regulated Dnmt3a expression, and loss of Dnmt3a reduced lesion growth and inflammatory cytokine production, thereby reversing immune dysregulation. These findings establish a mechanistic link between PCB-126 exposure and epigenetic and immune reprogramming in endometriotic lesions. Our findings establish a mechanistic connection between environmental PCB-126 exposure and endometriosis progression via the AXL/ESR2/DNMT3A axis. This study provides new insight into how endocrine-disrupting chemicals promote hormone-sensitive diseases through epigenetic and immunological pathways, offering potential targets for therapeutic intervention.
PMID:41054802 | DOI:10.1210/endocr/bqaf146
J Hazard Mater. 2025 Oct 4;499:140054. doi: 10.1016/j.jhazmat.2025.140054. Online ahead of print.
ABSTRACT
Contaminants of emerging concern (CECs), including pharmaceuticals and personal care products (PPCPs) and endocrine-disrupting chemicals (EDCs), have raised increasing concerns due to their persistence and potential ecological risks in freshwater systems. However, the spatial characteristics and source contributions of CECs in river networks remain insufficiently understood. In this study, we developed an integrated source apportionment framework by coupling spatial statistics, multivariate statistical analyses, and receptor model to unravel the dynamic and origins of CECs in the Changle River watershed. Widespread of CEC contamination was observed, with average total concentrations ranging from 66.2-191 ng L-1 and 51.4-498 ng L-1 in the main channel, and 105-477 ng L-1 and 39.3-1970 ng L-1 in tributaries across wet and dry seasons, respectively. Integrated spatial and multivariate analyses identified anthropogenic hotspots, with untreated sewage (37.6 %) and swine wastewater (39.5 %) as primary sources, while WWTP effluents contributed minimally (9.77 %). Network analysis further revealed pollutant correlations, implying shared geochemical behaviors or common origins. The results highlighted a complex interplay of point and non-point sources, underscoring the need for tailored source control and integrated watershed management strategies to reduce ecological and health risks posed by CECs.
PMID:41056720 | DOI:10.1016/j.jhazmat.2025.140054
Medicine (Baltimore). 2025 Oct 3;104(40):e44909. doi: 10.1097/MD.0000000000044909.
ABSTRACT
Environmental endocrine disruptors (EDCs) are chemicals that disrupt the endocrine system and pose significant health risks. Perceived sensitivity to illness refers to the heightened susceptibility of an individual due to genetic or environmental factors. This study aims to examine how the awareness of women on EDCs influences their motivation to adopt health behaviors, focusing on the mediating role of perceived illness sensitivity. From October to November 2024, we conducted a cross-sectional survey of 200 adult women in Seoul and Gyeonggi Province, South Korea. Participants were recruited from community-based institutions and completed an online questionnaire assessing their EDCs knowledge, perceived illness sensitivity, and motivation for health behaviors. Data were analyzed using descriptive statistics, parametric tests (t-test, ANOVA) for normally distributed variables, and nonparametric tests (Mann-Whitney U, Kruskal-Wallis) for non-normally distributed variables. Pearson correlations and mediation analysis were also performed. The average knowledge score on EDCs was 65.9 (SD = 20.7). Perceived illness sensitivity averaged 49.5 (SD = 7.4), and health behavior motivation was 45.2 (SD = 7.5). Significant differences in EDCs knowledge, perceived illness sensitivity, and health behavior motivation were observed based on age, marital status, education level, and menopausal status. EDCs knowledge positively correlated with perceived illness sensitivity and motivation. Perceived illness sensitivity was also positively linked to motivation. Mediation analysis revealed that perceived sensitivity partially mediated the relationship between EDCs knowledge and motivation. These findings suggest that knowledge alone may not be sufficient to promote behavior change; cognitive and emotional awareness of illness risk plays a key mediating role. Therefore, effective interventions should combine education with strategies to enhance perceived illness sensitivity.
PMID:41054081 | PMC:PMC12499794 | DOI:10.1097/MD.0000000000044909
Stem Cell Res Ther. 2025 Oct 7;16(1):545. doi: 10.1186/s13287-025-04481-5.
ABSTRACT
Sarcopenia, a progressive age-related decline in skeletal muscle mass and function, is closely linked to impaired regenerative capacity of satellite cells (SCs), also known as satellite cells. Age-dependent SCs dysfunction, driven by intrinsic senescence and niche dysregulation, disrupts activation, proliferation, and differentiation, thereby exacerbating regenerative deficits in sarcopenia. The SCs niche undergoes age-related remodeling, characterized by immune cell infiltration, ECM stiffening, and aberrant FAPs differentiation toward Fibro-Adipogenic lineages. Immune subsets orchestrate inflammation resolution and SCs activation during regeneration, while FAPs exhibit dual roles: transient pro-regenerative WISP1 secretion and chronic fibrotic conversion. Concurrently, vascular-neural networks sustain SCs quiescence and neuromuscular junction integrity, with age-related degradation of these systems exacerbating regenerative decline. Single-cell omics and 3D genomic studies have revealed heterotypic interactions and chromatin structural changes underlying SCs dysfunction in aging. Emerging therapeutic strategies targeting SCs rejuvenation and niche restoration-including metabolic regulation, endocrine interventions, and cell-based therapies-are complemented by advances in single-cell omics and 3D modeling technologies, which offer unprecedented opportunities to dissect niche complexity and identify novel therapeutic targets for sarcopenia. This review synthesizes recent advancements in understanding the role of SCs and their dynamic niche microenvironment in sarcopenia pathogenesis, exploring novel therapeutic strategies while underscoring the critical importance of deciphering their bidirectional interplay for developing effective interventions against age-related muscle loss.
PMID:41057931 | PMC:PMC12505871 | DOI:10.1186/s13287-025-04481-5
World J Urol. 2025 Oct 7;43(1):599. doi: 10.1007/s00345-025-05964-z.
ABSTRACT
OBJECTIVE: To systematically examine the association between chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and male infertility, elucidate the pathophysiological mechanisms by which CP/CPPS impairs fertility, summarize current research advancements, and establish a foundation for targeted diagnosis and treatment strategies.
METHOD: This study synthesizes clinical research, meta-analyses, and experimental model evidence to examine alterations in semen parameters (concentration, motility, morphology, DNA fragmentation rate) and seminal plasma biomarkers (PSA, cytokines, hormones). It explores the interactions across various systems, including neuro-immune-endocrine dysregulation, metabolic diseases, microcirculatory dysfunction, aberrant intestinal-prostate axis activity, and mitochondrial autophagy. The study assesses diagnostic frameworks such as NIH-CPSI and UPOINT, along with their therapeutic effectiveness.
RESULTS: CP/CPPS markedly decreased sperm concentration (SMD= - 14.12), forward motility (SMD= - 5.94), and normal morphology rate (SMD= - 8.26), while elevating DNA fragmentation rates (> 30%). Principal mechanisms comprise: (1) Pro-inflammatory cytokines (e.g., IL-6, TNF-α) impairing mitochondrial function and DNA integrity; (2) Neuroendocrine dysfunction inhibiting the hypothalamic-pituitary-testicular axis; (3) Metabolic syndrome comorbidity (OR = 2.10) inducing an energy crisis via mitochondrial dysfunction; (4) Gut microbiota dysbiosis diminishing anti-inflammatory short-chain fatty acids (SCFAs), intensifying systemic and reproductive tract inflammation; (5) Mitophagy impairments (e.g., PINK1 dysfunction) resulting in the accumulation of damaged sperm mitochondria. UPOINTs phenotype-guided multimodal therapy mitigates clinical symptoms, with 77.5% of patients attaining a reduction of at least 6 points in the NIH chronic prostatitis symptom index (NIH-CPSI) scores within 6 months.
CONCLUSION: The intricate pathogenesis of male infertility in CP/CPPS encompasses a diverse array of pathways: inflammatory, autoimmune, neuroendocrine, metabolic, and mitochondrial. Future investigations should concentrate on the mechanisms of mitochondrial autophagy and the regulation of epigenetics. Clinical management may contemplate the implementation of multidisciplinary, collaborative, phenotype-oriented, comprehensive therapies to disrupt the "chronic pain-inflammation-infertility" vicious cycle and protect fertility health.
PMID:41055724 | DOI:10.1007/s00345-025-05964-z
PLoS One. 2025 Oct 6;20(10):e0330476. doi: 10.1371/journal.pone.0330476. eCollection 2025.
ABSTRACT
The escalating decline in biodiversity in agroecosystems is a growing concern. Chemical pollutants such as plasticizers are increasingly implicated in this decline, with potential implications for both food production and quality. Among these pollutants, the endocrine-disrupting compounds (EDC) bisphenol A (BPA) and di(2-ethylhexyl) phthalate (DEHP) are particularly widespread and well documented in agricultural environments. Previous studies have reported the bioaccumulation of BPA and DEHP in crop plants, resulting in impaired growth and productivity. However, these findings were based on contaminant concentrations thousands of times exceeding those typically found in the environment. This raised critical questions about the real effects of BPA and DEHP on crop plants at environmentally relevant doses, particularly under conditions of single or combined exposure. This study investigated the effects of environmental doses of BPA and DEHP on tomato plants (Solanum lycopersicum), one of the most important crops in the world. Plants were exposed via root application to low and intermediate environmental concentrations (0.05 µg.L-1 BPA and 0.5 µg.L-1 DEHP or 50 µg.L-1 BPA and 10 µg.L-1 DEHP, respectively), under both mono- and co-exposure. The results revealed disruption in plant growth and productivity, which varied based on the specific EDC, concentration and exposure conditions.
PMID:41052045 | PMC:PMC12500100 | DOI:10.1371/journal.pone.0330476
Anal Chem. 2025 Oct 14;97(40):22418-22426. doi: 10.1021/acs.analchem.5c04922. Epub 2025 Oct 5.
ABSTRACT
Endocrine-disrupting chemicals, particularly estradiol (E2), pose significant risks to environmental and human health due to their persistence and bioactivity. In this study, we developed a highly sensitive and label-free electrochemical sensor for E2 detection, based on a glass micropipette (GMP) filled with polydopamine nanotubes (PDA-NTs) and coupled with a small molecule-induced DNA strand dissociation strategy. PDA-NTs self-assemble into a densely packed structure at the tip of the GMP, providing abundant binding sites for E2 aptamer (Apt) immobilization and achieving the first signal amplification, which yields a detection limit of 1.29 pM. To further enhance sensitivity, a partially complementary DNA (cDNA) strand was hybridized with the aptamer to form an Apt-cDNA duplex. Upon E2 binding, the Apt in the Apt-cDNA duplex undergoes a conformational change that releases the sterically large cDNA, resulting in a significant increase in ionic current and enabling the second signal amplification. This second amplification improves the detection limit by 112-fold, reaching as low as 11.5 fM. The sensor can detect E2 in the detection range of 10 fM-10 nM and demonstrates high selectivity in complex mixed solutions such as fetal bovine serum (FBS) and environmental water. Beyond highly sensitive detection of E2, this dual-signal amplification also allows the detection of other small molecules through aptamer sequence replacement.
PMID:41047530 | DOI:10.1021/acs.analchem.5c04922
Analyst. 2025 Oct 6. doi: 10.1039/d5an00465a. Online ahead of print.
ABSTRACT
Food contamination by phthalate esters (PAEs) is an emerging issue due to their ubiquitous behavior. They are present in foods as a result of migration from food packing. They are known as endocrine disruptors and present an environmental health risk. These characteristics pose analytical challenges in their assessment due to contamination during their analysis. In this work, we present a novel, highly functional analytical method for the analysis of six phthalates, namely dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butylphthalate (DBP), butyl benzyl phthalate (BBP), bis(2-ethylhexyl) phthalate (DEHP) and di-n-octyl phthalate (DNOP), in chicken fat tissues. For this purpose, we developed a simple but powerful extraction method without one of the major sources of analysis contamination, the clean-up with solid phase extraction cartridges. The innovation relies on the reduced steps of sample preparation, the minimal sample quantities and the minimal extraction solvent quantities by liquid-liquid extraction with methanol and detection by liquid chromatography with tandem mass spectrometry. The limits of quantification results for each target analyte in the chicken fat tissues were 0.25 μg kg-1 for DMP, 0.5 μg kg-1 for DEP, 1.25 μg kg-1 for DBP, 1.25 μg kg-1 for BBP, 2.5 μg kg-1 for DEHP and 2 μg kg-1 for DNOP, respectively. The calculated measurement uncertainty ranges from 7.2% to 16%. The present validated method was found to be precise, sensitive, and rapid to determine 6 PAEs in chicken fat tissues. This method also shows potential for application in other matrices such as water and food. This approach reduces solvent consumption, minimizes contamination risk, and aligns with the principles of Green Analytical Chemistry. Additionally, this method makes use of only 10 mg of sample, demonstrating that accurate quantification of trace contaminants is achievable with minimal sample amounts, as supported by recent miniaturized methodologies for fat-rich matrices.
PMID:41048086 | DOI:10.1039/d5an00465a
Postgrad Med. 2025 Oct 9:1-12. doi: 10.1080/00325481.2025.2571943. Online ahead of print.
ABSTRACT
BACKGROUND: Persistent shoulder pain is often driven by inflammatory conditions, including tendinopathy, bursitis, and frozen shoulder. Treatment remains uncertain, but targeting underlying mechanisms like inflammation, metabolic factors, and nervous system disturbances may be more effective.
OBJECTIVE: This perspective review summarizes these underlying mechanisms' roles in patients with inflammatory-driven shoulder pain and potential effective treatments for these mechanisms.
RESULTS: Literature links inflammatory-driven shoulder pain to low-grade inflammation, obesity, hypertension, diabetes mellitus, and/or autonomic and central nervous system disturbances, which are interconnected. Both acute and chronic inflammation are evident in tissue around the shoulder joint, potentially compromising treatment outcomes and predisposing tissue to hyperresponsiveness. Persistent inflammation can disrupt endocrine and nervous system functions, leading to additional health issues. Metabolic factors, characterized by low-grade inflammation, increase the risk for developing inflammatory-driven shoulder pain. Patients with inflammatory-driven shoulder pain often exhibit autonomic and somatosensory dysregulation. The autonomic nervous system's involvement in the inflammatory pathway can be influenced by or influence inflammation when dysregulation precedes shoulder pain development. Its pathways overlap with pain processing, potentially affecting each other. Prolonged stress (mental or biological) can lead to a maladaptive state and trigger somatosensory dysregulation. Interventions targeting these mechanisms go beyond the joint and include pain neuroscience education, exercise therapy, graded motor imagery, stress management, lifestyle interventions, and combinations of these. However, evidence specific to shoulder pain is limited.
CONCLUSION: Future research should prioritize understanding these underlying mechanisms in patients with inflammatory-driven musculoskeletal shoulder pain and evaluating targeted interventions' effects on shoulder disabilities.
PMID:41047816 | DOI:10.1080/00325481.2025.2571943
Front Endocrinol (Lausanne). 2025 Sep 18;16:1589826. doi: 10.3389/fendo.2025.1589826. eCollection 2025.
ABSTRACT
INTRODUCTION: Perfluorooctane sulfonate (PFOS), known as a critical endocrine disruptor, was linked to potential intergenerational effect in population studies. Yet, the toxic metabolic mechanisms remain unclear, particularly at relatively low PFOS concentration.
METHODS: This study investigated the metabolic impacts of early-life (pregnancy and lactation) PFOS exposure on adult Sprague-Dawley (SD) offspring rats using an integrated transcriptomics and metabolomics approach. Metabolic phenotypes, including glucose tolerance, lipids, and metabolic biomarkers were measured.
RESULTS: Early-life exposure to 0.03 mg/kg PFOS was found to be associated with elevated fasting and 15-minute blood glucose, serum insulin, and adiponectin levels and a decrease of leptin level in dose of 0.3 mg/kg was observed. Differentially expressed genes induced by PFOS exposure were enriched in NOD-like receptor signaling, parathyroid hormone synthesis, secretion and action, unsaturated fatty acid biosynthesis, insulin signaling, retinol metabolism, fatty acid metabolism, glucagon signaling, type II diabetes, and PPAR signaling. Differentially expressed metabolites were linked to citric acid cycle, glycerophospholipid metabolism, and fatty acid biosynthesis. Coenrichment analysis revealed feature changes in several pathways, including glycerophospholipid metabolism, sphingolipid metabolism, and primary bile acid synthesis (0.03 mg/kg), and retinol metabolism, linoleic acid metabolism, DGlutamine and D-Glutamine biosynthesis, and fatty acid elongation (0.3 mg/kg).
CONCLUSION: Early-life exposure to PFOS might lead to metabolic perturbations in adult offspring, which might be triggered by changes in pathways, i.g. glycerophospholipid metabolism, retinol metabolism, linoleic acid metabolism, and fatty acid elongation. Further validation of these pathways is required.
PMID:41048434 | PMC:PMC12488417 | DOI:10.3389/fendo.2025.1589826
Mol Biol Rep. 2025 Oct 6;52(1):986. doi: 10.1007/s11033-025-11101-1.
ABSTRACT
BACKGROUND: Disorders of sex development (DSDs) are rare conditions characterized by discordance among chromosomal, gonadal, or anatomical sex. NR0B1 (DAX1) gene dosage is known to play a key role in sex determination.
METHODS AND RESULTS: We report a phenotypically female infant with ambiguous genitalia and a rare chromosomal aberration: 45,Y, der(X)t(13;X)(q10;p22.3),-13 mat. Clinical findings included clitoromegaly, penoscrotal hypospadias, a single perineal opening, and nonpalpable gonads. Cystourethroscopy and laparoscopy revealed internal Müllerian structures and testicular tissue on the left. Chromosomal microarray analysis identified a 2.2 Mb duplication at Xp21.2-p21.1 encompassing NR0B1, a dosage-sensitive gene involved in sex determination. Despite the presence of SRY and testicular tissue, NR0B1 duplication likely antagonized testicular development, resulting in partial gonadal dysgenesis. The patient's mother harbored the same structural aberration with NR0B1 triplication but exhibited a normal phenotype, suggesting sex-limited expression and potential skewed X-chromosome inactivation.
CONCLUSIONS: This case demonstrates how structural chromosomal rearrangements can alter NR0B1 gene dosage and disrupt sex development, even in the absence of coding sequence mutations. The findings emphasize the importance of comprehensive genetic and endocrine evaluation in DSDs and illustrate the variable expressivity of NR0B1 duplication depending on sex and X-inactivation patterns.
PMID:41051607 | DOI:10.1007/s11033-025-11101-1
J Vis Exp. 2025 Sep 19;(223). doi: 10.3791/69000.
ABSTRACT
Premature ovarian insufficiency (POI) is a critical condition leading to female infertility, necessitating reliable animal models for mechanistic and therapeutic research. Here, we present a standardized protocol for establishing and evaluating a cyclophosphamide (CTX)-induced POI mouse model. Six-to-eight-week-old female mice with regular estrous cycles were selected and subjected to intraperitoneal CTX injections: an initial dose of 100 mg/kg on day 1, followed by daily doses of 20 mg/kg for the subsequent 14 days. Dynamic changes in estrous cycles were monitored via vaginal smear cytology with Wright staining. Serum levels of estradiol (E2), follicle-stimulating hormone (FSH), and anti-Müllerian hormone (AMH) were quantified using ELISA to assess endocrine alterations. Ovarian histopathology was evaluated through hematoxylin-eosin (H&E) staining of paraffin-embedded sections to quantify follicular atresia, while immunohistochemical analysis of cleaved caspase-3 was performed to detect granulosa cell apoptosis. Results demonstrated disrupted estrous cyclicity, significantly reduced E2 and AMH levels, elevated FSH concentrations, increased follicular atresia, and enhanced granulosa cell apoptosis in CTX-treated mice, confirming successful POI modeling. This model-building method can highly mimic the mechanism of chemotherapy-induced ovarian damage, presenting typical pathological features such as follicle reserve depletion and sex hormone disorders. It provides a reliable experimental platform for revealing the reproductive toxicity mechanism of chemotherapy, screening ovarian-protecting drugs, and optimizing fertility preservation strategies. Moreover, this model is relatively simple to operate, low-cost, and has a short production cycle, making it easy to carry out and popularize. The methodology aligns with the requirements of JoVE for visualizable, step-by-step experimental demonstrations.
PMID:41052002 | DOI:10.3791/69000
J Biol Chem. 2025 Oct 4:110782. doi: 10.1016/j.jbc.2025.110782. Online ahead of print.
ABSTRACT
The Human Exposome Project (HEP) aims to decode how lifelong environmental exposures shape health and disease, complementing genomic insights with a systems-level understanding of external influences. Achieving this vision requires experimental platforms that move beyond the limitations of animal models, which often lack human relevance and mechanistic resolution. Microphysiological systems (MPS)-including organoids and organs-on-chips derived from human stem cells-offer such an opportunity. These engineered models recapitulate human tissue architecture and function under controlled conditions, enabling direct study of exposure-response relationships at the cellular and organ level. In this review, we outline how MPS can serve as a foundation for exposome research by bridging epidemiological observations with mechanistic biology. We describe applications ranging from air pollutant toxicity to food contaminants, endocrine disruptors, and nanomaterials, highlighting how MPS integrated with omics technologies and artificial intelligence (AI) can reveal pathways of injury, identify biomarkers, and support the development of digital twins to simulate exposure-disease trajectories. We also discuss frameworks for validation, quality assurance, and transparent reporting, which are essential for reproducibility and regulatory acceptance. Finally, we consider ethical issues such as donor rights, data sovereignty, and equitable access, underscoring the importance of anticipatory governance. Together, MPS represent more than alternatives to animal testing-they are strategic enablers of a human-relevant, AI-empowered exposome science. By anchoring statistical associations in mechanistic data, MPS can accelerate translation into public health policies that are predictive, preventive, and personalized.
PMID:41052635 | DOI:10.1016/j.jbc.2025.110782
Ecotoxicol Environ Saf. 2025 Oct 1;304:119124. doi: 10.1016/j.ecoenv.2025.119124. Epub 2025 Oct 4.
ABSTRACT
Environmental endocrine disruptors (EEDs) are exogenous chemicals that impair physiological health by disrupting endocrine function. The gut-brain axis represents a complex bidirectional communication network integrating the gut microbiome, immune system, neural signaling, and endocrine pathways to maintain systemic homeostasis. Within this interconnected system, gut microbiota influence mood regulation, immune activity modulates neural processes, and neural signaling governs circadian and sleep cycles. This review explores the multi-system impacts of EEDs across four key physiological domains: (1) gut microbial ecology, (2) immune function, (3) neuroendocrine regulation, and (4) developmental processes. Evidence indicates that EED exposure disrupts intestinal microbial composition, leading to dysbiosis marked by the depletion of beneficial taxa and the expansion of pathogenic species. Concurrently, EEDs impair gut-associated immune cell populations (T cells, B cells, and macrophages), undermining mucosal immunity and increasing susceptibility to inflammatory bowel disease, autoimmune conditions, and gastrointestinal malignancies. At the endocrine level, EEDs interfere with the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes, contributing to hormonal imbalances and impaired reproductive development. Neurochemically, they disrupt the synthesis, release, and degradation of key neurotransmitters, including norepinephrine, dopamine, and serotonin, while exerting direct neurotoxic effects such as cerebrovascular abnormalities and delayed cerebellar myelination. In summary, this review delineates the mechanistic pathways through which EEDs perturb gut-brain axis homeostasis. These insights provide a scientific basis for designing targeted therapeutic interventions and shaping evidence-based public health policies.
PMID:41046701 | DOI:10.1016/j.ecoenv.2025.119124
Aquat Toxicol. 2025 Sep 26;289:107590. doi: 10.1016/j.aquatox.2025.107590. Online ahead of print.
ABSTRACT
Synthetic phenolic antioxidants (SPAs) are widely utilized in industrial production and consumer goods owing to their excellent antioxidant properties. However, their potential for multiple toxic effects, coupled with the increasing levels of environmental pollution, has heightened public concern. Currently, there is a relative scarcity of study on the reproductive toxicology of SPAs in hydrobios, with a particular dearth of studies in invertebrates. This study investigates the reproductive toxicity of the typical SPAs butylhydroxytoluene (BHT) in male clams Ruditapes philippinarum across distinct breeding period. The finding show that,the processes of meiosis and spermatogenesis were inhibited, leading to a decreased number of mature sperm and a reduced gonad index. Furthermore, an increase in reactive oxygen species (ROS) content was observed in the testes under BHT stress, causing biomacromolecular damage. BHT induces different types of cell death processes in testis cells, thereby damaging sperm development.Ultimately, this investigation clarifies the molecular basis for reproductive toxicity caused by BHT in invertebrates living in water. The research specifically analyzed contributing factors including endocrine disruption, epigenetic effects, and oxidative stress. The experimental results provide valuable data support for marine shellfish germplasm conservation and marine SPAs pollution detection.
PMID:41046803 | DOI:10.1016/j.aquatox.2025.107590
Environ Pollut. 2025 Oct 3;386:127206. doi: 10.1016/j.envpol.2025.127206. Online ahead of print.
ABSTRACT
Environmental contaminants such as polystyrene nanoplastics (PSNPs, 1-1000 nm) and glyphosate pose significant environmental and public health risks. This study aimed to investigate the intestinal toxicity and molecular mechanisms induced by PSNPs and/or glyphosate. Mice were exposed to PSNPs (<100 nm), glyphosate, or a combination of both for 35 days via intragastric administration (PSNPs: 0.5 mg/d; glyphosate: 50 mg/kg-bw/day; PSNPs + glyphosate: 0.5 mg/d +50 mg/kg-bw/day). The control group received same volume of distilled water. Our findings revealed that exposure to PSNPs and/or glyphosate aggravated pathological alterations, including inflammatory cell infiltration, severe mitochondrial cristae fracture, and an approximately 50 % reduction in goblet cells in the intestine. Moreover, exposure to PSNPs and/or glyphosate caused a critical 75 % inhibition of FOXP3 and dissociation of tight junctions in the intestine (reflected by a 50 % decrease in Occludin, and a 20 %-50 % decrease in ZO-1). These changes were accompanied by significant alterations in beneficial gut microbiota, metabolic profiles, bile acid metabolism disorders, and a pronounced elevation in 3-β-deoxycholic acid, a metabolite tied to bile acid receptor signaling and barrier dysfunction. Although exposure to glyphosate led to the most significant upregulation of the pro-inflammatory factors TNF-α and the pro-apoptosis proteins Cleave-caspase-3, co-exposure did not exacerbate cell apoptosis in animal tissue experiments, which is contrasts with the cell-based findings. MODE-K (mouse intestinal epithelial) cells were treated with PSNPs (0.75 mg/mL) or glyphosate (0.5 mg/mL). In vitro experiments showed that PSNPs aggravated the disrupted Treg/Th17 immune-inflammatory balance, impaired intestinal barrier function (with a 50 % reduction in ZO-1 and Occludin), and increased cell apoptosis, caused by glyphosate. This study advances our understanding of the health risks posed by endocrine-disrupting chemical mixtures and provides critical insights into the molecular mechanisms of PSNP-glyphosate-induced intestinal toxicity. These findings lay the groundwork for future research aimed at mitigating the pathophysiological impacts of environmental pollutants.
PMID:41047062 | DOI:10.1016/j.envpol.2025.127206
Anal Chem. 2025 Oct 14;97(40):22145-22152. doi: 10.1021/acs.analchem.5c04090. Epub 2025 Oct 5.
ABSTRACT
Bisphenol A (BPA), a typical endocrine-disrupting chemical, occurs in food samples due to its release from food packaging materials, posing a great exposure threat to human health. Selective and sensitive determination of released BPA from packaging materials is of great importance. Herein, we report a persistent luminescence aptasensor for the autofluorescence-free determination of released BPA from packaging materials with high selectivity and sensitivity. The proposed aptasensor was composed of BPA aptamer-functionalized Fe3O4 nanoparticles as the recognition and separation unit and complementary DNA (cDNA)-decorated ZnGeO4:Mn2+ (ZGM) as the persistent luminescence source. The developed aptasensor combined the merits of the autofluorescence-free determination from ZGM, high selectivity from the aptamer, and rapid separation from magnetic Fe3O4. The proposed aptasensor gave a wide linear range from 1 ng L-1 to 100 μg L-1 and a low detection limit of 0.036 ng L-1. The precision for the determination of 1 μg L-1 BPA was 5.0% (RSD, n = 11). The proposed aptasensor was applied for the determination of released BPA from food packaging materials. The results showed that photoaging and heating significantly increased the release of BPA from packaging materials to water, posing a significant toxicity risk to humans. The proposed aptasensor has potential extension in analyzing other kinds of analytes by simply replacing the aptamer and cDNA, providing a highly sensitive and selective autofluorescence-free platform for sensing hazardous analytes.
PMID:41046546 | DOI:10.1021/acs.analchem.5c04090
Ecotoxicol Environ Saf. 2025 Oct 1;304:119168. doi: 10.1016/j.ecoenv.2025.119168. Epub 2025 Oct 4.
ABSTRACT
Organophosphate esters (OPEs) are widely used flame retardants that have become ubiquitous in the environment. As typical environmental endocrine disruptors (EEDs), their adverse effects on human reproduction and development have raised global concern. In this study, we assessed the embryotoxicity of tris (1,3-dichloro-2-propyl) phosphate (TDCIPP, the most frequently detected OPEs in environment and human) and illustrated the molecular mechanisms in mouse embryos in vivo and in vitro. We found that exposure to 1 mg/kg⋅bw/day TDCIPP from gestational day (GD) 1 to GD14 significantly induced embryonic absorption and deformity in pregnant mice. Similar embryonic absorption and deformity were observed in in vitro fertilization (IVF) mice model after TDCIPP-treated embryos were transferred. Mechanistically, we found that exposure to TDCIPP downregulated the expression of leptin receptor (LEPR) and inhibited the downstream signaling pathway of interleukin 6 (IL6) /janus kinase 2 (JAK2) /signal transducer and activator of the transcription 3 (STAT3). In embryo culture system, the supplementation of 100 ng/mL IL6 or 50 ng/mL IL10 markedly alleviated TDCIPP-induced embryonic absorption and deformity. Collectively, our results suggest that the inhibition of LEPR-mediated IL6/JAK2/STAT3 signaling pathway might play a role in TDCIPP-induced embryotoxicity.
PMID:41046700 | DOI:10.1016/j.ecoenv.2025.119168
Mol Biol Rep. 2025 Oct 4;52(1):980. doi: 10.1007/s11033-025-11081-2.
ABSTRACT
Polycystic ovary syndrome (PCOS) is a complex, multifactorial metabolic and endocrine disorder in reproductive-age women. This review discusses the interlinked roles of lifestyle, metabolic dysregulation, insulin resistance, neuroendocrine impairment, genetic predisposition, and post-translational modifications (PTMs) in PCOS pathogenesis. Lifestyle components, especially those leading to obesity and insulin resistance, worsen the hyperandrogenism, ovulatory dysfunction, and inflammation. Dietary treatments such as, DASH diet and caloric restriction, particularly along with metformin, have been proven to improve metabolic and reproductive parameters. Environmental toxins, such as endocrine-disrupting chemicals (EDCs) and advanced glycation end-products (AGEs), further compromise ovarian function and hormone regulation. Oxidative stress and insulin resistance, driven by mitochondrial malfunction and chronic inflammation, create a self-perpetuating vicious cycle that compromises oocyte quality and worsens metabolic imbalance. Neuroendocrine disruption, characterized by increased GnRH and LH pulsatility, is initiated by dysregulated kisspeptin, dynorphin, and neurokinin B signaling in KNDy neurons, modified GABAergic input, and increased AMH and androgens. PTMs such as phosphorylation, methylation, acetylation, and ubiquitination also play essential roles in granulosa cell function, AR signaling, insulin sensitivity, and oocyte maturation. Current and novel treatment options vary from lifestyle modifications and pharmacological interventions (e.g., metformin, GLP-1 receptor agonists, myoinositol, vitamin D, and statins) to regenerative measures like mesenchymal stem cells and fecal microbiota transplantation. Newer therapies focusing on PTMs and neuroendocrine regulators remain the future hope. Multidisciplinary individualized management is critical for successful PCOS therapy and averting long-term complications.
PMID:41045390 | DOI:10.1007/s11033-025-11081-2
Environ Pollut. 2025 Oct 2;386:127203. doi: 10.1016/j.envpol.2025.127203. Online ahead of print.
ABSTRACT
Nanoplastics (NPs), an emerging and increasingly prevalent environmental pollutant, pose a significant threat to organisms. Although recent research has begun to elucidate the mechanisms underlying ovarian toxicity induced by NPs, the involvement of cellular interactions, particularly those involving immune cells, in ovarian injury remains poorly understood. Here, we established a murine model exposed to polystyrene nanoplastics over an 8-week period to explore the role of macrophages in NPs-induced ovarian injury. Our in vivo results demonstrated that NPs accumulated in ovarian tissues, leading to ovarian endocrine disruption and follicular atresia, concomitant with macrophages infiltration and the formation of macrophage extracellular traps (METs). Complementary investigation using a co-culture system of macrophages and granulosa cells (GCs) indicated that NPs-induced METs triggered pyroptosis of GCs, and this biological crosstalk could be mitigated by DNase I. Further transcriptomic analysis revealed that NPs prompted macrophages to release METs through activating the PI3K-Akt signaling pathway. Notably, LY294002, a specific inhibitor of the PI3K-Akt pathway, significantly suppressed METs formation and consequently rescued GCs pyroptosis and ovarian injury induced by NPs. In summary, our findings uncover the mechanistic role of METs in exacerbating ovarian injury induced by NPs, and highlight the PI3K-Akt signaling pathway as a potential therapeutic target.
PMID:41045980 | DOI:10.1016/j.envpol.2025.127203
Toxicology. 2025 Oct 2:154296. doi: 10.1016/j.tox.2025.154296. Online ahead of print.
ABSTRACT
Organophosphate pesticides (OPs) have found extensive use in agriculture due to their short half-lives and relatively low persistence in the environment. In recent years, a growing body of evidence has linked OPs, including chlorpyrifos (CPF), to endocrine, reproductive, and metabolic dysfunction, raising significant public health concerns. Although CPF has been linked to various toxic effects, the epigenetic mechanisms underlying CPF-induced hepatotoxicity remain poorly understood. In the present study, mice were orally exposed to CPF (2 or 20mg/kg body weight), and the effects on hepatic function were assessed. CPF exposure resulted in pronounced hepatotoxicity characterized by increased oxidative stress, impaired mitochondrial function and dysregulated expression of genes involved in oxidative phosphorylation. Notably, CPF exposure significantly depleted hepatic choline levels and downregulated the expression of genes involved in the regulation of DNA methylation, including Dnmt1, Mthfr and Tet2. The decline in hepatic choline was correlated with hypomethylation of the hepatic genome in CPF-exposed mice. CPF also elevated serum corticosterone in mice, reinforcing its role as an endocrine disruptor. This hormonal disruption was associated with dysregulated glucose homeostasis as evidenced by glucose intolerance, elevated hepatic glycogen and altered hepatic expression of the glucose transporter Glut2. Together, the findings from this study provide novel mechanistic insights into the epigenetic and metabolic effects of CPF-induced hepatotoxicity.
PMID:41046031 | DOI:10.1016/j.tox.2025.154296
bioRxiv [Preprint]. 2025 Sep 27:2025.09.26.677825. doi: 10.1101/2025.09.26.677825.
ABSTRACT
Transcriptional regulation is a key central mechanism of cell fate determination in developing tissues. The homeobox transcription factor NKX2.2 is an essential regulator of mouse and human pancreatic endocrine development, however its precise molecular role in a human system has not been previously investigated. In this study we generated NKX2.2 null (NKX2.2KO) human embryonic stem cell (hESC) lines using CRISPR/Cas9 technologies and differentiated them towards a pancreatic β cell fate using a stem cell-derived β cell differentiation protocol. Functional and transcriptomic analyses of the hESC-derived pancreatic endocrine cells lacking NKX2.2 revealed similarities and differences compared to the molecular functions of NKX2.2 in mice. In the absence of NKX2.2, the β cell differentiations result in reduced numbers of insulin-producing cells, and the differentiations become skewed towards polyhormonal fates, including cells co-expressing insulin, ghrelin and somatostatin. Deletion of NKX2.2 also eliminates the off-target formation of enterochromaffin cells. Single cell transcriptome analysis of the early endocrine cell population revealed a marked disruption of metabolic pathways that was confirmed by comparative metabolite tracing, providing novel insights into the regulation of early endocrine lineage decisions. Furthermore, NKX2.2 directly regulates several genes in the WNT signaling pathway, suggesting this is a key molecular mechanism through which NKX2.2 regulates these islet cell fate decisions in the human system.
PMID:41040286 | PMC:PMC12485700 | DOI:10.1101/2025.09.26.677825
Cell Biol Toxicol. 2025 Oct 3;41(1):134. doi: 10.1007/s10565-025-10095-7.
ABSTRACT
4-Nonylphenol (NP) is an environmental endocrine disruptor widely used in consumer products. Previous studies have shown that NP can interfere with hormone synthesis and metabolism in humans and animals, leading to male reproductive dysfunction. This study utilized the scRNA-seq method to evaluate cell populations and their heterogeneity, aiming to elucidate the toxic mechanisms of NP exposure on testicular cells. We demonstrate, for the first time, the transcriptomic characteristics of testicular single cells in adolescent mice exposed to NP. Adolescent mice, initially exposed at 4 weeks of age, were subsequently analyzed at sexual maturity after a continuous exposure period of 3 months. The blank control and NP-exposed groups underwent scRNA-seq analysis, identifying ten cell populations. The results showed that after NP exposure, the number of germline cells was remarkably reduced compared to the control group. NP exposure significantly decreased the protein expression of the four common differentially expressed genes (DEGs) (Cmtm2b, Rpl28, Adam32, and Pgam2). The DEGs enriched in the GO functions of the four germline cell types were spermatogenesis and spermatid development. KEGG analysis showed that the DEGs were enriched in the oxidative phosphorylation, and ROS signaling pathways. Further analysis of intercellular interactions revealed that NP exposure altered intercellular communication between germ cells, with the NECTIN3-NECTIN2 receptor-ligand interactions activating between spermatogonia, Sertoli, and Leydig cells. Germ cells bind to Sertoli and Leydig cells via NECTIN3-NECTIN2 receptor ligands. Somatic cells bind to RS and ES through GRN-SORT1 receptor ligands. CADM1-CADM1 receptor-ligand interactions enhances between germ and Sertoli cells. Our study provides new insights into the potential impacts of NP on spermatogenesis and sperm function, emphasizing the importance of environmental hormones in male fertility issues.
PMID:41042295 | PMC:PMC12494639 | DOI:10.1007/s10565-025-10095-7
Environ Res. 2025 Oct 1:123004. doi: 10.1016/j.envres.2025.123004. Online ahead of print.
ABSTRACT
Pollution by pharmaceuticals and industrial chemicals has received increased attention due to their environmental persistence and ecotoxicity as emerging contaminants (ECs). American alligators (Alligator mississippiensis) are top predators in the coastal aquatic ecosystems of the Gulf of Mexico and are a sentinel species for ecosystem health due to their longevity and high trophic position. However, knowledge on the extent of ECs exposures and likely health impacts on alligators is scarce. This study measured select ECs and blood biochemistry parameters in alligator plasma opportunistically sampled at the Rockefeller Wildlife Refuge in southwest Louisiana. The analysis showed the prominent occurrence of 6 ECs in the plasma: amphetamine (AMP), atenolol (ATN), ketoprofen (KTP), naproxen (NPR), nicotine (NCT), and perfluorooctane sulfonate (PFOS). AMP and PFOS were most prevalently detected in the plasma samples (95% and 100% detection frequency, respectively), and exhibited the highest concentrations (mean ± SEM; AMP: 7.05 ± 3.02 ng/mL, PFOS: 5.95 ± 0.57 ng/mL). The detection of the other ECs ranged from 46 - 69% and with mean concentrations approximately an order of magnitude lower than that of PFOS or AMP. While the biochemistry parameters were all within physiologically acceptable ranges, partial redundancy and correlation analyses suggested positive correlations between the total number of detected pharmaceuticals, ATN, and PFOS, with biochemical parameters associated with liver, kidney, and muscle injury; and endocrine disruption. This study reports on the exposure of alligators to ECs and identifies likely biomarkers of exposure and adverse effects.
PMID:41043507 | DOI:10.1016/j.envres.2025.123004
Environ Toxicol Pharmacol. 2025 Oct;119:104834. doi: 10.1016/j.etap.2025.104834. Epub 2025 Oct 1.
ABSTRACT
Breast cancer is the most common malignancy in women, and environmental factors such as endocrine-disrupting chemicals (EDCs) contribute to its development and progression. This review examines the roles of four major EDCs-bisphenols, polychlorinated biphenyls (PCBs), parabens, and dioxins-integrating mechanistic and epidemiological evidence. A key pathway is the cross-talk between estrogen receptor (ER) and aryl hydrocarbon receptor (AhR), which regulates proliferation, survival, and immune evasion. Bisphenol A (BPA) promotes proliferation, migration, epigenetic reprogramming, and immune escape. PCBs, particularly PCB-153, are linked to metabolic alterations, inflammation, and variable epidemiological associations. Parabens, common in cosmetics, display estrogenic activity and affect oxidative stress, tumor marker expression, and metastasis. Dioxins, especially TCDD, act via AhR to induce inflammation, immunosuppression, and metastasis, with epidemiological links to cancer risk near emission sources. Collectively, these EDCs disrupt hormonal pathways, alter gene expression, and modulate the tumor microenvironment, underscoring the need for further research, regulation, and public health interventions.
PMID:41043533 | DOI:10.1016/j.etap.2025.104834
Sci Rep. 2025 Oct 3;15(1):34559. doi: 10.1038/s41598-025-17931-0.
ABSTRACT
Acetyl tributyl citrate (ATBC) and epoxidized soybean oil (ESBO) are widely used emerging plasticizers, but their potential to induce lipid metabolism disorders remains poorly understood. In this study, we explored their toxicological mechanisms using a network toxicology framework combined with molecular docking and molecular dynamics simulations. Potential targets of ATBC and ESBO were predicted from multiple databases and compared with genes associated with lipid metabolism disorders. Core targets were identified through protein-protein interaction network analysis. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Disease Ontology (DO) enrichment analyses were performed to infer relevant biological processes and pathways. Molecular docking and dynamics simulations were further applied to evaluate the binding affinity and stability between the compounds and key targets. Five core targets-epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT3), toll-like receptor 4 (TLR4), JUN proto-oncogene (JUN), and androgen receptor (AR)-were identified, mainly involved in immune regulation, hormone signaling, and the hypoxia-inducible factor 1 (HIF-1) pathway. Enrichment analyses suggested that the emerging plasticizers ATBC and ESBO may disturb lipid metabolism and contribute to diseases such as non-alcoholic fatty liver disease (NAFLD) and hormone-sensitive cancers. Docking results confirmed strong and specific interactions between the compounds and core targets. Overall, these findings support the hypothesis that ATBC and ESBO may disrupt hepatic lipid metabolism through HIF-1 activation and immune-endocrine pathway interference, providing insight into their potential health risks.
PMID:41044206 | PMC:PMC12494788 | DOI:10.1038/s41598-025-17931-0
EFSA J. 2025 Sep 30;23(9):e9639. doi: 10.2903/j.efsa.2025.9639. eCollection 2025 Sep.
ABSTRACT
On 29 January 2021, the EFSA Panel on Plant Protection Products and their Residues adopted a Statement on acetamiprid in response to a mandate from the Commission following a notification under Article 69 of Regulation (EC) No 1107/2009 in which, among others, it was recommended to conduct an assessment of the endocrine disrupting (ED) properties of acetamiprid in line with the criteria established by Commission Regulation (EU) No 2018/605. On 27 March 2024, EFSA issued a Statement on the toxicological properties and maximum residue levels of acetamiprid and its metabolites, following a mandate from the Commission pursuant to Article 31 of Regulation (EC) No 178/2002. EFSA concluded that there are data gaps in the in vivo body of evidence, including the lack of an acceptable measurement of learning and memory, motor activity and morphometric evaluation in the available developmental neurotoxicity (DNT) studies. To account for the identified gaps, EFSA proposed to include an additional uncertainty factor of 5 in the derivation of the Health-Based Guidance Values: as a consequence, it could not be fully established that acetamiprid still meets the approval criteria laid down in Article 4 of Regulation (EC) No 1107/2009 with respect to its DNT, as well as for the ED properties for which an assessment is not available. Therefore, the European Commission decided to launch a review of the existing approval in accordance with Article 21 of that Regulation and invited the applicant to submit a comprehensive list of existing or planned studies, along with any relevant information, for re-assessing the ED and DNT properties of acetamiprid. On 21 May 2025, pursuant to Article 21(2) of Regulation (EC) No 1107/2009, the Commission requested EFSA to assess the proposal, as submitted by the applicant, on the testing strategy and associated timelines for the generation of additional data for the assessment of the DNT and ED properties of acetamiprid. The current statement contains EFSA's considerations whether the proposed studies are considered sufficient and realistic to complete the assessment of the ED properties of the active substance in line with Commission Regulation (EU) 2018/605 and to conduct an evaluation of DNT properties in line with the recommendations given in the EFSA statement issued in 2024.
PMID:41036495 | PMC:PMC12481163 | DOI:10.2903/j.efsa.2025.9639
Aquat Toxicol. 2025 Sep 23;289:107587. doi: 10.1016/j.aquatox.2025.107587. Online ahead of print.
ABSTRACT
Cortisone is a commonly found in a variety of aquatic environments and has potential adverse effects on aquatic organisms. This study was to assess the chronic toxic effects of cortisone at different concentrations (0.0, 5.0, 50.0 and 500.0 ng/L) for 60 days on adult female western mosquitofish (Gambusia affinis). The results revealed that cortisone significantly increased the proportion of perinuclear oocytes concomitant with reduced the prevalence of late-stage oocytes, indicating arrested oocyte maturation. Meanwhile, exposed females exhibited compromised mate attraction and diminished courtship interactions. Transcriptomic profiling of the ovaries identified significant enrichment of steroidogenic pathways (p < 0.001), with the differentially expressed gene CYP21A2 demonstrating pronounced up-regulation relative to that of the control fish. Gene expression and plasma steroid analyses further showed decreased expression of key genes in the hypothalamic-pituitary-gonadal (HPG) (lhb, fshb, gnrh2, gnrh3, and cyp19a1b in the brain; cyp19a1a and hsd20b in the ovary), whereas ovarian star, cyp17, hsd3b, and hsd17b3 were up-regulated. This transcriptional dysregulation disrupted plasma steroid homeostasis, manifested by significantly decreased levels of estradiol and 17α,20β-dihydroxy-4-pregnen-3-one (17α,20β-DHP), contrasted with a pronounced increase in 11-ketotestosterone. Vitellogenin gene transcription was also suppressed in both liver and brain tissues. Collectively, cortisone exposure induced endocrine disruption in G. affinis, which may ultimately compromise population stability. These findings provided valuable information for further understanding the potential ecological risks of corticosteroids.
PMID:41038008 | DOI:10.1016/j.aquatox.2025.107587
Cardiovasc Diabetol. 2025 Oct 1;24(1):381. doi: 10.1186/s12933-025-02938-8.
ABSTRACT
Endocrine-disrupting chemicals (EDCs) are exogenous compounds that interfere with hormone action, and growing evidence suggests that human exposure to certain EDCs may increase the risk of obesity, type 2 diabetes mellitus (T2DM), and cardiovascular disease (CVD). To clarify the impact of EDC exposure on cardiometabolic health, we conducted a review of the literature (2005-2025) to identify both human epidemiological studies and animal mechanistic studies. In this narrative review, we primarily summarize the existing human epidemiological evidence on the cardiometabolic effects of EDCs, while also considering mechanistic insights, including selected animal studies, to illustrate biological plausibility. Key findings indicate that EDC exposures are consistently associated with elevated risks of cardiometabolic conditions. Notably, prenatal and early-life EDC exposures appear to increase susceptibility to obesity, impaired glucose metabolism, and cardiovascular dysfunction later in life, while adult exposures are linked to a higher incidence of metabolic syndrome, type 2 diabetes, and related cardiovascular complications. In conclusion, this review underscores EDC exposure as a significant environmental risk factor for cardiometabolic disease. Accordingly, strengthening regulatory policies to reduce human exposure to these chemicals-alongside further research into underlying mechanisms-may be crucial for improving cardiometabolic health outcomes.
PMID:41035032 | PMC:PMC12487381 | DOI:10.1186/s12933-025-02938-8
Front Med (Lausanne). 2025 Sep 15;12:1583203. doi: 10.3389/fmed.2025.1583203. eCollection 2025.
ABSTRACT
The interplay between steroid hormones (reproductive and stress hormones) and mental and physical health has evolved as an important area of medical and psychological research. At the same time, endocrine disrupting compounds (EDCs) spreading via our planet's water have become a focus in environment- and health-related sciences, as well as in the public interest. The impact of EDCs on the delicate hormonal balance essential to human health remains insufficiently understood. The Federal Ministry of Health in Germany deemed this topic so important that it tasked the German Environment Agency with conducting a nationwide, effect-directed analysis of EDCs in drinking water. Our interdisciplinary research collaboration, providing its scientific foundation, includes expertise from medicine, psychology, biology, ecotoxicology, technology, and artificial intelligence. The objective of this review is the assessment of endocrine effects caused by drinking water on the human body and the reduction of EDCs in the urban water cycle emitted by the human body. Our specific goals are to gain a better understanding of human psychoneuroendocrine health in relation to the EDC problem, to identify gaps in current research and to explore measures for reducing the human body's emissions of EDCs. This assessment is particularly relevant given the anticipated global rise in the use of contraceptives, infertility treatments, hormone-replacement therapies and endocrinological treatments of stress-related disorders, all of which contribute to increased endocrine-disrupting compounds in the water cycle. Leveraging artificial intelligence and virtual human twin technologies to simulate individualized hormonal responses provide valuable insights into possible targeted interventions for reducing EDCs by personalized endocrinological practice.
PMID:41030262 | PMC:PMC12477257 | DOI:10.3389/fmed.2025.1583203
Anim Microbiome. 2025 Sep 30;7(1):97. doi: 10.1186/s42523-025-00463-3.
ABSTRACT
BACKGROUND: Declines in honey bee queen quality and variability in drone (male) reproductive performance are contributing factors to colony losses reported by beekeepers. While the causes of reduced reproductive fitness remain unclear, recent evidence implicates agrichemical exposure. Oxytetracycline (OTC), an antibiotic used in apiculture for over 70 years to treat brood diseases, is classified as an endocrine-disrupting compound due to its inhibition of mitochondrial function in reproductive cells. In other animals, OTC exposure has been associated with impaired reproductive development, reduced sperm viability, and broader reproductive dysfunction. Although the effects of OTC on worker bee gut microbiota and physiology are well documented, its impact on drone gut microbiota has never been characterized. Additionally, we recently discovered microbial communities in drone reproductive tissues, which could be impacted by OTC exposure. The goal of this study was to determine if OTC has the potential to impact drone development, survival, fecundity, and microbiota composition.
RESULTS: Using an in vitro rearing system, we found that larval OTC exposure delays drone development, reduces survival, and results in detectable residues in the gut and reproductive tissues of newly emerged adults. In mature drones, oral exposure to conservative field-relevant OTC concentrations significantly reduced gut bacterial abundance and diversity, although reproductive tissue-associated microbiota appeared largely unaffected. In vitro assays further revealed that OTC is highly toxic to drone sperm at environmentally relevant concentrations.
CONCLUSION: Our findings demonstrate that OTC exposure has the potential to negatively affect drone development, survival, gut microbiota, and sperm viability. These results support our hypothesis that the use of OTC in beekeeping may contribute to reduced male reproductive health. Importantly, this work highlights the need for additional studies, particularly field-based investigations, to better understand the impacts of OTC on drone reproductive health and microbiomes. Such research will be critical for evaluating the broader consequences of antibiotic use in apiculture and for developing sustainable strategies to manage brood diseases.
PMID:41029790 | PMC:PMC12482078 | DOI:10.1186/s42523-025-00463-3
Biol Trace Elem Res. 2025 Oct 1. doi: 10.1007/s12011-025-04832-6. Online ahead of print.
ABSTRACT
Cadmium (Cd), a ubiquitous heavy metal pollutant with significant environmental persistence and bioaccumulative potential, poses a severe threat to human health and ecological safety. As a widely recognized endocrine disruptor, Cd has attracted sustained research attention in environmental and public health domains due to its multifaceted toxicity. Recent advances in regulated cell death mechanisms have revealed ferroptosis is a distinct form of cell death (apoptosis, autophagy, necroptosis, and pyroptosis) characterized by iron overload and lipid peroxidation. A novel insight highlighted in this review is the direct linkage between Cd toxicity and ferroptosis, which provides a new perspective for understanding the toxic mechanism of Cd. This review systematically synthesizes emerging evidences on Cd-induced ferroptosis. Cd triggers ferroptosis by impairing mitochondrial structure and function, disrupting iron metabolism, promoting lipid peroxidation, and suppressing antioxidant systems. Notably, therapeutic interventions using selenium and melatonin have protective effect on Cd-induced ferroptosis by modulating iron metabolism, enhancing ROS scavenging capacity, and restoring redox balance. Future research priorities should focus on elucidating key molecular events in Cd-induced iron dysregulation. This review underscores the translational potential of targeting ferroptosis in Cd toxicity mitigation strategies, offering a mechanistic framework for environmental intervention and therapeutic innovation.
PMID:41034599 | DOI:10.1007/s12011-025-04832-6
Food Sci Nutr. 2025 Sep 28;13(10):e71021. doi: 10.1002/fsn3.71021. eCollection 2025 Oct.
ABSTRACT
Critical information regarding the interactions among food components, human metabolism, and disease is contained in foodomics, an interdisciplinary field that bridges food science with contemporary omics technologies (genomics, proteomics, metabolomics, and lipidomics). In order to gain a better understanding of the metabolic dysregulation in type 2 diabetes mellitus (T2DM), foodomics examines bioactive compounds derived from food (e.g., polyphenols, fibers, and lipids) alongside host molecular responses. For the enhancement of glycemic control and the prevention of diabetes-related complications, the current study is concerned with how foodomics enables personalized dietary interventions that are aligned with one's metabolic and genetic characteristics. We investigate deeper into the role of the gut microbiota in T2DM progress and how foodomics-informed methodologies, such as metabolomics and metagenomics, can be functional to discover treatments intended at the microbiota. In addition, we discover the prospective that functional foods enriched with bioactive elements, comprising β-glucans and flavonoids, may influence metabolic processes in diabetes. In addition, foodomics improves food safety by recognizing conceivable diabetes-causing contaminants (endocrine disruptors). Foodomics has incredible potential for improving precision nutrition in the prevention and treatment of T2DM, though experiments in data integration and standardization are present. Through the integration of dietary concepts, molecular biology, and clinical consequences, this method offers revolutionary strategies towards metabolic wellness.
PMID:41030838 | PMC:PMC12477330 | DOI:10.1002/fsn3.71021
Int J Gynaecol Obstet. 2025 Oct 1. doi: 10.1002/ijgo.70549. Online ahead of print.
ABSTRACT
Environmental exposures are increasingly recognized as critical, yet underappreciated, determinants of reproductive, perinatal, and early childhood health. Developed through a structured consensus process and grounded in systematic evidence review, this FIGO committee opinion provides a comprehensive synthesis of the current evidence linking environmental toxicants-including air pollution, endocrine-disrupting chemicals, heavy metals, and climate-related stressors-to common obstetric outcomes such as preterm birth, hypertensive disorders of pregnancy, gestational diabetes, and impaired fetal growth, as well as to early childhood outcomes including neurodevelopmental delay, metabolic disease, and atopic conditions. This article also outlines common biological mechanisms, such as endocrine disruption, oxidative stress, epigenetic modification, and placental dysfunction, and provides clinicians with actionable guidance for integrating environmental health into reproductive care through screening, counseling, and advocacy. Special attention is paid to the role of social and structural inequities in amplifying exposure risks and health disparities. By linking environmental drivers to familiar clinical outcomes, this guidance empowers obstetricians and allied professionals to engage in preventive care that safeguards maternal and child health across the life course. FIGO calls on reproductive health professionals to embrace this leadership role-not only in clinical practice, but in shaping policies that protect current and future generations.
PMID:41031523 | DOI:10.1002/ijgo.70549
Int J Gynaecol Obstet. 2025 Oct 1. doi: 10.1002/ijgo.70552. Online ahead of print.
ABSTRACT
Micro-and nanoplastics (MNPs) are breakdown products of plastics, and humans are exposed to these particles through air, water, food, and soil. There is a growing concern that human exposure to MNPs negatively impacts health. In this review we will discuss the potential health impact of MNPs on ovarian function and the hypothalamic-pituitary-ovarian (HPO) axis. We will highlight that the deleterious effects of MNPs on female reproductive health have been mostly documented in animal models. Studies have demonstrated that MNPs accumulate in ovarian tissue, disrupt hormonal signaling, and induce oxidative stress, leading to hormonal irregularities, ovarian atrophy, and increased androgen levels. Additionally, there is accumulating evidence that not only are MNPs a concern by themselves, but they are also carriers of endocrine-disrupting chemicals (EDCs) which further exacerbate reproductive dysfunction. While animal models demonstrate reproductive toxicity from MNP exposure, there are gaps in our knowledge on whether these findings can be translated to humans. Human clinical trials to directly determine the impact of MNPs are unethical because the evidence suggests MNP exposure may be detrimental to health. In this review, we highlight gaps in our knowledge and suggest areas which need further research.
PMID:41031521 | DOI:10.1002/ijgo.70552
Environ Int. 2025 Sep 28;204:109820. doi: 10.1016/j.envint.2025.109820. Online ahead of print.
ABSTRACT
Bisphenol A (BPA) is a widely encountered environmental endocrine disruptor with detrimental effects on embryonic development and implantation. Conventional reproductive toxicity tests often rely on animal-derived gametes or embryos. However, these approaches are invasive and limited in their ability to assess early germline development. To address these limitations, we used a synthetic embryo model derived from pluripotent stem cells (PSCs) to evaluate BPA-induced embryotoxicity without using actual oocytes or embryos. Mouse PSCs were converted into chemically induced totipotent-like stem cells (ciTotiSCs) using a defined small-molecule combination. These ciTotiSCs generated blastoids (ciToti-blastoids) through three-dimensional aggregation in inverted pyramid-shaped microwell plates (AggreWell system) and cultured for 5 d. To investigate the impact of environmental toxicants on early embryogenesis, blastoids were exposed to 5 μM BPA during formation. Blastoid formation efficiency was reduced to approximately 14 % following treatment with 5 μM BPA, compared with approximately 73 % in the control. To assess implantation potential, established blastoids were further cultured on the Matrigel-coated dish. BPA-treated blastoids exhibited a reduction in inner cell mass (ICM) area and in trophectoderm (TE) area, approximately 96 % and 72 %, respectively, indicating impaired implantation potential. These detrimental effects of BPA were accompanied by elevated reactive oxygen species (ROS) levels during ciToti-blastoid formation. Co-treatment with the antioxidant glutathione (GSH; 0.5 mM), a ROS scavenger, restored blastoid formation efficiency (approximately 54 %) and resulted in a similar normalized ICM and TE areas comparable to control. Transcriptomic analysis revealed that BPA induced endoplasmic reticulum stress, DNA damage, and apoptosis, all of which were mitigated by GSH treatment. These results highlight the role of oxidative stress in BPA-induced embryotoxicity and support the utility of stem cell-derived blastoid models as egg-free platforms for assessing the reproductive toxicity of environmental chemicals.
PMID:41033068 | DOI:10.1016/j.envint.2025.109820
J Assist Reprod Genet. 2025 Oct 1. doi: 10.1007/s10815-025-03653-9. Online ahead of print.
ABSTRACT
PURPOSE: Environmental pollution is a growing global concern, yet its effects on reproductive health remain poorly understood. While numerous epidemiological studies have identified strong associations between exposure to pollutants and adverse reproductive outcomes, the precise biological mechanisms underlying these effects remain elusive.
METHODS: A comprehensive literature search was performed by two reviewers using the US National Library of Medicine (NCBI Pubmed) up to August 15, 2025.
RESULTS: Chemical and physical contaminants, including endocrine-disrupting chemicals (EDCs), particulate matter (PM), heavy metals, and heat stress (HS), have been implicated in disrupting of essential reproductive processes, such as gametogenesis, fertilization, implantation, and embryogenesis. Despite accumulating evidence, the complexity of these interactions has hindered the development of targeted interventions and effective regulatory policies.
CONCLUSIONS: This review argues that investment in reproductive environmental research is not only necessary but urgent. The pervasive nature of pollution and its potential long-term consequences on fertility and pregnancy outcomes warrant an intensified focus on mechanistic studies, improved environmental monitoring, and the integration of toxicological data into reproductive medicine. It is imperative to prioritize research that can provide the necessary insights to mitigate these threats. This paper highlights the knowledge gaps, emphasizing the need for a multidisciplinary approach that combines epidemiology, toxicology, and molecular biology to inform policies and safeguard reproductive health.
PMID:41032203 | DOI:10.1007/s10815-025-03653-9
Pathol Res Pract. 2025 Sep 29;275:156251. doi: 10.1016/j.prp.2025.156251. Online ahead of print.
ABSTRACT
Polycystic Ovary Syndrome (PCOS) is a multifactorial endocrine-metabolic disorder characterized by reproductive irregularities, hyperandrogenism, and insulin resistance. Recent advances in chronobiology have introduced a compelling narrative suggesting that dysregulation in circadian system is a contributing factor in the pathogenesis and clinical manifestation of PCOS. This review explores how disrupted biological timing-reflected in misaligned central and peripheral clocks, altered melatonin dynamics, and irregular sleep-wake cycles-intersects with metabolic and hormonal dysfunctions in PCOS. We highlight emerging evidence linking aberrant expression of clock genes such as CLOCK, BMAL1, and PER1 in ovarian, hepatic, and hypothalamic tissues to ovulatory failure, insulin resistance, and androgen excess. Moreover, melatonin, a key circadian hormone, demonstrates altered systemic and follicular profiles in PCOS, influencing folliculogenesis, oxidative stress, and steroidogenesis. Further, this review delves into the neuroendocrine pathways by which circadian cues modulate the hypothalamic-pituitary-ovarian axis and how their disruption may contribute to reproductive impairment. In light of these findings, we discuss chronotherapeutic approaches-including melatonin supplementation, time-restricted feeding, light therapy, and circadian-timed pharmacotherapy-as emerging strategies for personalized and temporally aligned PCOS treatment. Despite limitations in clinical standardization and the need for biomarker-based stratification, chronomedicine offers a promising adjunct to traditional PCOS management. By framing PCOS as a disorder of temporal dysregulation, this review advocates for a paradigm shift in both understanding and treating the syndrome, paving the way toward circadian-informed clinical care.
PMID:41033089 | DOI:10.1016/j.prp.2025.156251
Environ Int. 2025 Sep 28;204:109825. doi: 10.1016/j.envint.2025.109825. Online ahead of print.
ABSTRACT
OBJECTIVE: To evaluate the association of individual and mixed exposure to endocrine-disrupting chemicals (EDCs) with hyperactivity trajectories in preschoolers.
METHOD: This study used data from a cohort of 823 preschoolers. Baseline urine samples measured concentrations of 22 EDCs (T0). Follow-ups occurred twice, every six months (T1 and T2), with mothers completing hyperactivity questionnaires at all time points (T0-T2). Latent class growth analysis (LCGA) was used to assess children's hyperactivity trajectories. We investigated the individual and joint effects of EDCs using binary logistic regression, quantile-based g-computation (Q-gcomp) model, and Bayesian kernel machine regression (BKMR) model, respectively.
RESULTS: We identified two hyperactivity trajectories: the "high hyperactivity trajectory" and the "low hyperactivity trajectory". The binary logistic regression results showed that nine chemicals were significantly associated with hyperactivity trajectories (OR = 0.57 ∼ 2.37, 95 % CI: 0.33-4.03). The Q-gcomp model showed a positive association between mixed EDC exposures and the hyperactivity trajectories (OR = 2.13, 95 % CI: 1.70-2.66). The BKMR model found a significant positive relationship between the EDC mixtures and hyperactivity trajectories when all chemical concentrations were at or above their 55th percentile compared with the median. After stratification by gender, we found that exposure to EDC mixtures was more strongly associated with hyperactivity trajectories in girls.
CONCLUSION: The current study indicates the adverse health effects of exposure to mixtures of EDCs among preschoolers, and suggests gender specificity in these effects. This highlights the importance of focusing on multi-pollutant exposure in early childhood and taking targeted interventions.
PMID:41033069 | DOI:10.1016/j.envint.2025.109825
Chemosphere. 2025 Nov;389:144702. doi: 10.1016/j.chemosphere.2025.144702. Epub 2025 Oct 1.
ABSTRACT
Air pollution is closely associated with increased lung cancer incidence and mortality. Because many semi-volatile industrial chemicals, pesticides and combustion by-products are endocrine-disrupting or genotoxic, their mixtures in outdoor urban air, even at trace levels, could have cumulative effects. However, evidence for the impact of outdoor air pollution on human health remains limited, partly because its composition is poorly characterized. Non-targeted analysis (NTA) based on the combination of liquid (LC) and gas (GC) chromatographic separation with high resolution mass spectrometry (MS), allows for the comprehensive analysis of contaminants in environmental samples. Here, we present the first application of an NTA approach using both LC- and GC-MS to characterize the chemical mixture in outdoor urban air by analyzing forty passive samplers deployed for 82 days during summer 2021 across the Island of Montreal, Canada. The confirmed 25 molecular features included nitrophenols, pesticides/repellents, plasticizers, organophosphorus compounds, organohalogen compounds, other industrial chemicals, and natural products. Triethylene glycol monomethyl ether, triethylene glycol monobutyl ether, n-octyl-pyrrolidone, quinoline n-oxide, 4-hydroxy-acetophenone, citric acid, 2-phenyl acetamide, and hexachloroethane were detected for the very first time in the atmosphere. Previously reported in atmospheric particles, 4-nitrophenol, 2,4-dinitrophenol, tri- and tetraethylene glycol, nonanoic acid, diethylene glycol dibenzoate, caprolactam, phenylacrylic acid, pinonic acid and triphenylphosphine oxide were also detected in the outdoor atmospheric gas phase. The spatial grouping of data between residential and public areas emphasizes the impact of anthropogenic activities on atmospheric vapor composition. This study facilitates the assessment of airborne exposure to chemical mixtures and its effects on human health.
PMID:41033295 | DOI:10.1016/j.chemosphere.2025.144702
Toxicol Lett. 2025 Sep 29;413:111732. doi: 10.1016/j.toxlet.2025.111732. Online ahead of print.
ABSTRACT
BACKGROUND: Bisphenol A (BPA) is a widespread endocrine-disrupting chemical found in consumer products. While BPA exposure has been associated with various health risks, its specific impact on colorectal cancer (CRC) progression and underlying mechanisms remain poorly understood.
METHODS: In this five-year retrospective cohort study, we analyzed 63 CRC patients selected from an initial cohort of 574. Urinary BPA was quantified using HPLC-MS/MS, and patients were stratified into normal (n = 15), low (n = 30), and high (n = 18) BPA exposure groups. Flow cytometry and immunohistochemistry profiled immune cell populations in blood and tumor tissues. Multivariate regression analyses identified relationships between BPA exposure, metabolic parameters, and clinical outcomes.
RESULTS: BPA levels showed significant inverse correlations with HDL/LDL ratio (p = 0.010) and positive correlations with BMI (p = 0.028). Patients with high BPA exposure demonstrated significantly higher rates of metastasis (61.1 % vs. 10 % in low exposure and 0 % in normal exposure groups, p < 0.001) and shorter overall survival (median 20 months vs. 51 months in low exposure group, p = 0.034). Flow cytometric analysis revealed dose-dependent reductions in circulating CD8 + T cells, CD4 + T cells, and NK cells with increasing BPA exposure. Immunohistochemical analysis showed pronounced decreases in tumor-infiltrating CD8 + T lymphocytes correlating with BPA exposure levels (p = 0.0027). High BPA exposure was also significantly associated with increased post-surgical infection rates (OR=1.9, 95 % CI: 1.1-3.1).
CONCLUSION: These preliminary findings suggest BPA exposure represents a potential risk factor for CRC progression, likely mediated through metabolic alterations and immunosuppression within the tumor microenvironment. Environmental exposures may significantly influence cancer outcomes through immune-metabolic pathways, though further validation in larger cohorts is warranted.
PMID:41033586 | DOI:10.1016/j.toxlet.2025.111732
Commun Med (Lond). 2025 Oct 1;5(1):410. doi: 10.1038/s43856-025-01119-8.
ABSTRACT
BACKGROUND: Bisphenol A (BPA) is an endocrine disruptor, and exposure to low doses in utero has been associated with the development of metabolic diseases. Previous studies have suggested that bone marrow (BM) may be particularly susceptible to BPA exposure.
METHODS: Here, we investigate how developmental exposure to low levels of BPA affects the BM transcriptome and the blood metabolic profile in Fischer 344 rats later in life. We compare these effects to those observed in human metabolic syndrome (MetS) using a population-based cohort.
RESULTS: The results show an unexpectedly extensive sex-biased effect on the BM transcriptome from a BPA dose approximately eight times lower than the recent temporary European Food Safety Authority (EFSA) human tolerable daily intake (TDI) and a higher dose considered safe in 2015. BPA exposure induces sex-specific changes in gene expression, progressing toward a hypometabolic cancer-like state in females and a hypermetabolic autoimmunity-like state in males, with a blood metabolic profile that significantly overlaps with human MetS in a cross-sectional study.
CONCLUSIONS: We conclude that developmental low-dose BPA exposure might induce metabolic syndrome specifically in males, possibly by affecting T cell activity in a sex-specific manner. Our study provides biologically plausible and convincing evidence for significant effects from low-dose BPA exposure, supporting the substantial lowering of the human BPA TDI by EFSA based on its critical effects on T cells.
PMID:41034487 | PMC:PMC12488919 | DOI:10.1038/s43856-025-01119-8
BMC Public Health. 2025 Sep 30;25(1):3220. doi: 10.1186/s12889-025-24093-1.
ABSTRACT
BACKGROUND: Rapidly increasing evidence has documented that endocrine disruptors (EDs) contribute substantially to disease and disability, particularly neurodevelopmental disorders, metabolic diseases, reproductive disorders, immune and thyroid dysfunctions, as well as hormone-related cancers. These conditions can lead to chronic impairments and disability, such as learning and behavioral difficulties, infertility, long-term treatment dependence, or reduced functional capacity. Biomonitoring studies conducted in France have shown widespread exposure of the general population to several endocrine disruptors (phthalates, bisphenols, pesticides, PCBs, etc.), with particularly high levels observed among children. However, there is still too little epidemiological surveillance data. To address this gap, Santé publique France has undertaken a project to prioritize the health effects to be surveilled in relation to EDs, considering both scientific and societal criteria. Scientific criteria included the strength of evidence for ED-related causality, severity of health outcomes, and data availability. Societal criteria considered public concern, perceived vulnerability, and relevance to policymaking.
METHODS: We conducted a consultation with experts and French stakeholders in the field of EDs using the Delphi consensus method from November 2021 to June 2022. A list of 59 health effects was submitted for prioritization.
RESULTS: Several effects were prioritized by all the participants according to scientific, epidemiological and societal criteria, including certain effects on neurodevelopment in children (attention deficit disorder with or without hyperactivity, autism spectrum disorder), the metabolic system (e.g. overweight and obesity) and reproductive health (e.g. endometriosis, breast cancer, alteration in sperm quality, etc.).
CONCLUSION: Based on the results of this consultation, Sante publique France will develop an integrated ED-related health surveillance strategy to identify and prioritize effective prevention strategies and actions in a context of uncertainty and lack of knowledge.
PMID:41029561 | PMC:PMC12486999 | DOI:10.1186/s12889-025-24093-1
Int J Gynaecol Obstet. 2025 Oct 1. doi: 10.1002/ijgo.70552. Online ahead of print.
ABSTRACT
Micro-and nanoplastics (MNPs) are breakdown products of plastics, and humans are exposed to these particles through air, water, food, and soil. There is a growing concern that human exposure to MNPs negatively impacts health. In this review we will discuss the potential health impact of MNPs on ovarian function and the hypothalamic-pituitary-ovarian (HPO) axis. We will highlight that the deleterious effects of MNPs on female reproductive health have been mostly documented in animal models. Studies have demonstrated that MNPs accumulate in ovarian tissue, disrupt hormonal signaling, and induce oxidative stress, leading to hormonal irregularities, ovarian atrophy, and increased androgen levels. Additionally, there is accumulating evidence that not only are MNPs a concern by themselves, but they are also carriers of endocrine-disrupting chemicals (EDCs) which further exacerbate reproductive dysfunction. While animal models demonstrate reproductive toxicity from MNP exposure, there are gaps in our knowledge on whether these findings can be translated to humans. Human clinical trials to directly determine the impact of MNPs are unethical because the evidence suggests MNP exposure may be detrimental to health. In this review, we highlight gaps in our knowledge and suggest areas which need further research.
PMID:41031521 | DOI:10.1002/ijgo.70552
Pediatr Res. 2025 Oct 1. doi: 10.1038/s41390-025-04425-y. Online ahead of print.
ABSTRACT
OBJECTIVE: Elevated maternal testosterone (T) during pregnancy disrupts neurodevelopment and behavior in offspring, mimicking features of autism spectrum disorder (ASD).
METHODS: In a rat study, dams received daily T injections (0.5 mg/kg) from gestational days 12-20, doubling maternal plasma T to mimic levels seen in pregnancy complications. Controls received vehicle. Offspring were assessed neonatally (postnatal day 9) for communication (ultrasonic vocalizations), neurogenesis (NeuN+ neurons), myelination (MBP+ area), and brain docosahexaenoic acid (DHA). Adolescent offspring (6-8 weeks) underwent behavioral tests for cognition (Y-maze, novel object recognition) and sociability (three-chamber test).
RESULTS: T-exposed pups had lower birth weights and reduced vocalizations during maternal separation. Sex-specific neural changes observed: males showed reduced cortical neuron density, while females had diminished corpus callosum myelination. Both sexes exhibited decreased brain DHA. In adolescence, T offspring displayed cognitive deficits (impaired spatial/recognition memory) and social impairments (reduced sociability and social novelty preference).
CONCLUSION: The study highlights maternal T as a risk factor for neurodevelopmental disorders, with sex-specific effects on brain structure and function. Reduced brain DHA suggests a mechanistic link, implicating lipid metabolism in T-associated neurodevelopmental disruptions. These findings support further exploration of DHA supplementation as a therapeutic strategy to mitigate adverse outcomes in high-risk pregnancies.
IMPACT: Elevated maternal testosterone (T) during pregnancy induces ASD-like neurobehavioral deficits (e.g., impaired communication, social/cognitive dysfunction) and sex-specific neural alterations in offspring. Prenatal T differentially impacts male vs. female brain structure: T-exposed males show cortical neuron loss, while females exhibit myelination deficits in the corpus callosum. First to connect maternal T-driven offspring brain docosahexaenoic acid (DHA) reduction to neurodevelopmental impairment. Supports prenatal DHA supplementation as a strategy to mitigate neurodevelopmental risks in high-T pregnancies. Informs policies addressing rising neurodevelopmental disorder rates linked to maternal metabolic/endocrine imbalances.
PMID:41034646 | DOI:10.1038/s41390-025-04425-y
Hum Reprod. 2025 Sep 30:deaf180. doi: 10.1093/humrep/deaf180. Online ahead of print.
ABSTRACT
Obesity is a global health concern with major implications for male reproductive function. It disrupts endocrine and metabolic homeostasis, impairs semen quality, and is associated with reduced pregnancy and live birth rates. Hormonal imbalances, inflammation, and lipid stress are key contributors to these impairments. This mini-review summarizes current evidence on the impact of therapeutic interventions, including lifestyle modification, bariatric surgery, and pharmacological approaches such as glucagon-like peptide-1 (GLP-1) receptor agonists, on male fertility outcomes. Lifestyle interventions, particularly moderate-intensity exercise and dietary improvements, are first-line therapies and should be routinely encouraged. Caloric restriction and Mediterranean-style diets rich in antioxidants have been associated with improved semen quality and hormonal balance. Bariatric surgery raises testosterone levels and may improve sperm quality and assisted reproduction outcomes in some men, but declines in sperm concentration and cases of postoperative azoospermia have also been reported. These findings underscore the importance of preoperative fertility counselling and consideration of sperm cryopreservation. GLP-1 receptor agonists promote weight loss and may improve sperm motility and hormonal markers; however, isolated cases of reversible impairment in sperm quality have been reported. Despite growing clinical use of these interventions, it remains unclear whether the observed benefits stem from weight loss itself or the specific treatment modalities. Longitudinal studies are needed to determine whether fertility improvements translate into higher conception rates. The reproductive safety of GLP-1 agonists in the preconception period also warrants further investigation. We recommend prioritizing pragmatic clinical trials with functional fertility endpoints, as well as mechanistic studies in well-characterized male obesity phenotypes and evaluation of offspring health. Ultimately, a shift is necessary from a narrow focus on weight loss to a broader emphasis on enhancing metabolic health. Personalized approaches tailored towards hormonal profiles, comorbidities, and fertility goals, supported by behavioural counselling and multidisciplinary care, are essential for advancing the treatment of obesity-related male infertility.
PMID:41024420 | DOI:10.1093/humrep/deaf180
Environ Sci Technol. 2025 Sep 30. doi: 10.1021/acs.est.5c03364. Online ahead of print.
ABSTRACT
Population models have long been thought of as a suitable approach for assessing the population relevance of chemical effects observed on individuals in laboratory studies, although they have rarely been applied in a regulatory context. We modeled potential population-level responses of individual-level adverse effects induced by endocrine-disrupting chemicals (EDCs). We imposed three effect durations (10-year, 3 months summer, or winter) for six common EDC endpoints (fecundity, fertilization rate, sex ratio: male and female skew, courtship and nesting behavior) at four magnitudes of effect (10, 20, 50 and 90% reduction) using individual-based population models for three fish species with differing life histories: stickleback (Gasterosteus aculeatus), brown trout (Salmo trutta) and zebrafish (Danio rerio). The suitability of different assessment criteria for determining the significance of population responses was evaluated. For all endpoints tested individually, effect magnitudes of 20% did not result in any population-level responses in each of the three species, except in the stickleback, where a 20% reduction in fecundity or fertilization rate led to population declines (in these cases, effect magnitudes of 10% did not result in population-level responses). Once standardized, our "exposure-agnostic molecule-independent" approach will enhance our understanding of population outcomes within the regulatory hazard-based assessment of EDCs.
PMID:41026511 | DOI:10.1021/acs.est.5c03364
Food Chem. 2025 Sep 18;495(Pt 2):146465. doi: 10.1016/j.foodchem.2025.146465. Online ahead of print.
ABSTRACT
Endocrine disrupting chemicals (EDCs) are emerging environmental pollutants. The present study focused on evaluating the concentrations of EDCs in packed coffee. Among 12 investigated EDCs, only DEP, DEHP, DnBP, BPA, and BPF were found in packed coffee (20 %, 40 %, 80 %, 20 %, and 20 %, respectively). The mean values ranged from 0.230 ng/g for BPA to 23.214 ng/g for DnBP. DnBP was the most frequently detected EDC in coffee powder (60 %), followed by DEP, DEHP, BPA, and BPF (20 % each). Migration assessment showed that DEHP, DnBP, and BPF amounts were significantly higher after coffee preparation in the traditional coffee maker (2.515 vs 2.192 ng/mL, 1.845 vs 1.491 ng/mL, and 0.177 vs < LD ng/mL). The levels of phthalates and BPA did not exceed the specific migration limits (SMLs) and the estimated daily intake (EDI) to EDCs were low. Hazard quotients (HQs) were below 1.0 for general and highly exposed populations.
PMID:41027375 | DOI:10.1016/j.foodchem.2025.146465
Environ Res. 2025 Sep 28;286(Pt 3):122967. doi: 10.1016/j.envres.2025.122967. Online ahead of print.
ABSTRACT
Biochar has gained significant attention in organic wastewater treatment due to its cost-effectiveness, eco-friendliness, and high adsorption and catalytic properties. This study reviews the preparation and modification strategies for biochar, including the carbonization of biomass, activation, and heteroatom doping, as well as the development of composite materials based on biochar. The adsorption and degradation mechanisms for removing pollutants were emphasized, and the differences between the radical and non-radical pathways in the degradation process of advanced oxidation processes (AOP) were clarified. The applications for removing organic pollutants such as antibiotics, dyes, polycyclic aromatic hydrocarbons (PAHs), and endocrine-disrupting chemicals (EDCs) were also summarized. Especially, the review highlights the transformative role of machine learning (ML) in biochar, particularly in optimizing production, predicting pollutant removal efficiency, and guiding material design. ML models such as Random Forest (RF) and Artificial Neural Networks (ANN) have demonstrated high accuracy in predicting biochar performance based on pyrolysis conditions, biochar characteristics, and experimental parameters. Furthermore, the challenges and future research directions in the field of biochar treatment of organic wastewater were discussed. By promoting the integration of ML and biochar design and application, providing meaningful guidance for further development of biochar in organic wastewater treatment.
PMID:41027493 | DOI:10.1016/j.envres.2025.122967
On 29 January 2021, the EFSA Panel on Plant Protection Products and their Residues adopted a Statement on acetamiprid in response to a mandate from the Commission following a notification under Article 69 of Regulation (EC) No 1107/2009 in which, among others, it was recommended to conduct an assessment of the endocrine disrupting (ED) properties of acetamiprid in line with the criteria established by Commission Regulation (EU) No 2018/605.
Anal Chim Acta. 2025 Nov 15;1375:344570. doi: 10.1016/j.aca.2025.344570. Epub 2025 Aug 25.
ABSTRACT
BACKGROUND: As plastic consumption increases annually, a concerning volume of plastic waste gathers in the environment. The lengthy process of breaking down these large plastic pieces into microscopic particles is accompanied by a steady leakage of chemicals added during production into the environment, which then enters the human body through the ecosystem. However, developing portable, reliable, and fouling-resistant electrochemical sensors to detect trace levels of plasticizers (endocrine disruptors) in the human body remains a significant analytical challenge.
RESULTS: This study introduces a dual-modified electrochemical platform using a carbon fiber microelectrode (CFME) coated with gold nanostructures and agar hydrogel infused with copper phthalocyanine (CuPc). This rational regulation of multicomponents at tiny interfaces is attributed to the synergistic interactions between the excellent electrical conductivity of gold nanolayers, the hydrophilicity, biocompatibility, and antifouling properties of hydrogels, and the homogeneous distribution of electrocatalytically active sites of CuPc. Bisphenol A (BPA), a typical representative of plasticizers, was used as a model to evaluate the performance of the designed functional microelectrodes. The results show that the plentiful Cu-N4 catalytic sites in CuPc provide exceptional electrocatalytic efficiency for BPA, with the reaction being diffusion-controlled. Additionally, the response demonstrates good linearity and reproducibility across a broad concentration range. Under optimal conditions, the sensor maintained high selectivity for BPA in the presence of potential interferents in blood samples and achieved a remarkable detection limit of 420 nM.
SIGNIFICANCE: This work introduces a microelectrode functionalization method that thoughtfully regulates multiple components at microinterfaces to create synergistic effects. It offers a versatile and adaptable sensing strategy, making it easier to detect trace plasticizers with high sensitivity and selectivity. This method unlocks exciting opportunities for real-time environmental and biomedical monitoring, paving the way for truly impactful applications.
PMID:41022506 | DOI:10.1016/j.aca.2025.344570
Sci Rep. 2025 Sep 29;15(1):33655. doi: 10.1038/s41598-025-17874-6.
ABSTRACT
This study investigated the effects of 17β-estradiol (E2) on male goldfish, with particular focus on how social interactions modify physiological responses. Four experimental groups were housed in 80 L tanks and received two injections at 14-day intervals over 28 days: MF (5 males + 5 females, sesame oil), M (10 males, sesame oil), MEF (5 males + 5 females, E2), and ME (10 males, E2). The MF group exhibited the highest growth performance, with significantly greater final weight (36.3 ± 1.1 g), weight gain (11.3 ± 1.4 g), and specific growth rate (1.8 ± 0.2% day⁻1) (P < 0.05). E2 exposure disrupted biochemical parameters, elevating cholesterol and triglycerides while reducing glucose and phosphorus (P < 0.05). Testosterone levels were significantly lower in E2-treated groups, with MF maintaining the highest levels (P < 0.05). Sperm activity and motility were severely impaired in E2-treated groups, with MF showing the highest sperm activity (95.6%) and motility time (371.2 sec) (P < 0.05). Gonadosomatic index was highest in MF (5.99%) but significantly reduced in MEF (4.56%), indicating gonadal impairment (P < 0.05). E2 exposure and social isolation inhibited spermatogenesis, reducing spermatogonia and spermatocytes. Liver histopathology revealed severe damage in ME, while MF displayed optimal hepatic structure. These results highlight the negative impact of E2 exposure on growth, reproduction, and liver function, while social interactions mitigated some effects. This underscores the complex interplay between endocrine disruption, social dynamics, and physiological health in goldfish.
PMID:41022892 | PMC:PMC12480994 | DOI:10.1038/s41598-025-17874-6