Endocrine Disruption

Front Immunol. 2025 Mar 19;16:1436589. doi: 10.3389/fimmu.2025.1436589. eCollection 2025.

ABSTRACT

BACKGROUND: In the realm of public health, late human immunodeficiency virus (HIV) diagnosis remains prevalent and is associated with neuropsychiatric adverse events. However, there is limited documentation regarding the impact of late HIV diagnosis (LD) on brain integrity, neurotrophic factors, endocrine function, and immunity in HIV-positive men who have sex with men (MSM).

METHODS: Participants (38 LD and 34 non-LD of MSM) underwent comprehensive infectious disease and psychiatric assessments, multimodal magnetic resonance imaging (MRI) scans, neurotrophic factors, endocrine, and immunological evaluations. Immune cell levels, along with peripheral plasma concentrations of neurotrophic factors and hormones, were measured using enzyme-linked immunosorbent assays and flow cytometry, respectively. T1-weighted images along with resting-state functional MRI were applied to assess brain function and structure while also examining correlations between imaging alterations and clinical as well as peripheral blood variables. The data for this study originated from a subset of the cohort in HIV-associated neuropsychiatric disorders research.

RESULTS: Compared to participants in the non-LD group, those in the LD group showed a lower total gray matter volume (GMV), with reduced GMV primarily observed in the left supramarginal gyrus. Participants in the LD group exhibited differences in brain function with certain regions and decreased functional connectivity between these altered regions and connected structures. A two-way factorial analysis of variance examining the main effects and interactions between groups and neuropsychiatric disorders revealed significant main effects of LD on specific brain regions. Furthermore, we found that individuals in the LD group had higher levels of cortisol, a lower frequency of central memory T cells, and elevated expression levels of perforin in double-negative T cells. These imaging findings were significantly correlated with endocrine, immune, and clinical variables.

CONCLUSION: This study suggests that LD may contribute to brain injury, endocrine disruption, and immune dysregulation in HIV-positive MSM. Consequently, there is an urgent need to develop public health strategies targeting late diagnosis, with a focus on strengthening screening and early detection for high-risk populations, as well as monitoring brain injury, endocrine, and immune functions in individuals with LD, and formulating precise, individualized intervention strategies to reduce the long-term impact of LD on the health of HIV-positive MSM.

PMID:40176812 | PMC:PMC11961418 | DOI:10.3389/fimmu.2025.1436589

Zhonghua Yu Fang Yi Xue Za Zhi. 2025 Apr 6;59(4):516-525. doi: 10.3760/cma.j.cn112150-20240715-00570.

ABSTRACT

Organic ultraviolet absorbers (OUVs) have been widely used in personal care products and industrial products due to their unique physicochemical properties. However, with the advancement of science and technology and the deepening of research, the potential risks of OUVs have gradually emerged. They have been proven to be persistent, bioconcentrated and potential endocrine disruptors that may pose a threat to human health. In recent years, some OUVs have been widely detected in environmental and human samples worldwide, and the concentration of detection has been increasing year by year, which has attracted extensive attention both domestically and internationally. This article summarizes the research results of OUVs exposure in recent years from two aspects: external environmental exposure and internal human exposure, aiming to provide a valuable reference for the subsequent research on human exposure and health risk assessment of OUVs.

PMID:40176676 | DOI:10.3760/cma.j.cn112150-20240715-00570

Front Endocrinol (Lausanne). 2025 Mar 19;16:1539063. doi: 10.3389/fendo.2025.1539063. eCollection 2025.

ABSTRACT

Non-obstructive azoospermia (NOA) constitutes one of the most severe forms of male infertility. Recent advancements in single-cell sequencing have significantly contributed to understanding the molecular landscape of NOA in human testicular tissues, elucidating the factors that underpin spermatogenic dysfunction. This technology has improved our understanding of the condition at a cellular level. Concurrently, bioinformatics developments have facilitated the re-analysis of publicly available single-cell datasets, offering novel insights into the disorder. Nevertheless, a comprehensive review integrating primary and re-analysis studies of single-cell sequencing in NOA is lacking. This review systematically evaluates 10 primary studies reporting original single-cell sequencing data of human NOA testicular samples and 22 secondary studies that re-analyzed these published data. We explore single-cell sequencing applications in germ cells, Sertoli cells, and Leydig cells, offering a comprehensive overview of molecular insights into spermatogenic dysfunction. Our review highlights novel findings in secondary studies, including the roles of transcriptional regulators, RNA transcription, endocrine disruptors, and microtubular cytoskeleton, thereby bridging primary studies and re-analysis studies. Additionally, we discussed future research directions and the challenges of translating single-cell research findings into clinical applications. In summary, single-cell sequencing offers a high-resolution, single-cell perspective of NOA testicular tissue, paving the way for innovative therapeutic strategies in male infertility.

PMID:40177631 | PMC:PMC11961434 | DOI:10.3389/fendo.2025.1539063

Environ Sci Technol. 2025 Apr 3. doi: 10.1021/acs.est.4c10565. Online ahead of print.

ABSTRACT

Sodium p-perfluorous nonenoxybenzenesulfonate (OBS) as a novel surrogate for perfluorooctanesulfonate (PFOS) has been extensively utilized in industrial manufacturing and daily life. However, studies on OBS-induced environmental health risks of obstructive biosynthesis (OBS) are currently limited, particularly the risk for thyroid diseases. Following the construction of in vivo (mouse) and in vitro (normal human primary thyrocytes) models of subchronic low-dose OBS exposure, we explored the thyroid-disrupting effects of OBS through multiomics approaches and experimental validations. Our results showed that subchronic exposure to low doses of OBS led to primary hypothyroidism in mice, presenting with reduced number and functional abnormalities of thyrocytes. Further in vitro assays confirmed that low-dose OBS-induced disulfidptosis, a newly discovered form of programmed cell death, in human primary thyrocytes. Meanwhile, exposure to low-dose OBS remarkably suppressed thyroid hormone synthesis pathways in mouse and human thyrocytes. The charted multiomic landscape of OBS-induced primary hypothyroidism in mammals revealed the thyroid toxicity and endocrine-disrupting properties of OBS, suggesting that it is not a safe alternative to PFOS.

PMID:40178189 | DOI:10.1021/acs.est.4c10565

Chem Res Toxicol. 2025 Apr 3. doi: 10.1021/acs.chemrestox.4c00455. Online ahead of print.

ABSTRACT

Nuclear receptors form a family of proteins capable of accommodating a wide variety of small molecules in their ligand binding domain, ranging from therapeutic compounds to endocrine-disrupting chemicals. The rapid identification of these compounds, especially within the latter category, is of paramount importance. Using data extracted from the CompTox Dashboard, an Environmental Protection Agency initiative, we assessed the effectiveness of a combination of molecular docking and pharmacophore models in identifying ligands binding to six nuclear receptors: androgen receptor, estrogen receptor alpha, estrogen receptor beta, glucocorticoid receptor, peroxisome proliferator-activated receptor gamma, and thyroid hormone receptor alpha. For each nuclear receptor, we selected a specifically designed and optimized in silico protocol that, in conjunction with experimental assays, can prioritize compounds for further evaluation to detect any potential toxicological concerns.

PMID:40178351 | DOI:10.1021/acs.chemrestox.4c00455

J Agric Food Chem. 2025 Apr 2. doi: 10.1021/acs.jafc.5c00224. Online ahead of print.

ABSTRACT

Bis(2-ethylhexyl) phthalate (DEHP) is an endocrine disruptor that may cause damage to several species. Quercetin (Que), a common flavonoid, has anti-inflammation, antioxidation, and immune regulation properties. In this study, we identified DEHP-exposed or Que-antagonist groups in chicken and MSB-1 cells to explore whether Que can mitigate DEHP-caused bursa of Fabricius pyroptosis and necroptosis. The findings demonstrated that Que reduced the expression of necroptosis and pyroptosis, inhibited the mitogen-activated protein kinase (MAPK)/NF-κB pathway, and mitigated oxidative stress caused by DEHP. The addition of the reactive oxygen species activator (Sanguinarin) raised the extent of oxidative stress, and the NF-κB activator (nuclear factor-kappa-B activator1, NF-κB act1) activated the MAPK/NF-κB pathway compared to the Que + DEHP group. In conclusion, Que inhibited the MAPK/NF-κB pathway to counteract DEHP-induced bursa pyroptosis and programmed necrosis. This work adds to the toxicological consequences of DEHP on avian further theoretical justification for Que's treatment of organic toxic damage.

PMID:40176274 | DOI:10.1021/acs.jafc.5c00224

Chem Res Toxicol. 2025 Apr 3. doi: 10.1021/acs.chemrestox.5c00030. Online ahead of print.

ABSTRACT

The ever-increasing use of chemicals and the rising incidence of adverse reproductive effects in the modern environment have become an emerging concern. Several studies have shown that environmental contaminants, such as organophosphate flame retardants (OPFRs), negatively impact reproductive health. To evaluate the potential endocrine-related adverse reproductive effects of widely used and priority-listed compound 2-Ethylhexyl diphenyl phosphate (EHDPP), we characterized its effects on adrenal steroidogenesis in human adrenocortical (H295R) cells. The cells were exposed to EHDPP (1 and 5 μM) for 48 h, and the production of hormones, including progesterone, androstenedione, testosterone, estradiol, cortisol, and aldosterone, was measured. In addition, LC-MS/MS-based lipidomics analysis was done to quantify intracellular lipid profiles, and transcriptional assays were performed to examine the expression of genes related to corticosteroidogenesis, lipid metabolism, and mitochondrial dynamics. Our findings indicate that EHDPP disrupts hormone regulation in vitro, as evidenced by increased estradiol, cortisol, and aldosterone secretion. The expression of key corticosteroidogenic genes (CYP11B2, CYP21A1, 3β-HSD2, and 17β-HSD1) was upregulated significantly upon EHDPP exposure. Intracellular lipidomics revealed EHDPP-mediated disruption, including reduced total cholesterol ester, sphingolipids, and increased phospholipids, triglyceride species, and saturated-monounsaturated lipids subspecies. These alterations were accompanied by decreased ACAT2 and SCD1 gene expression. Moreover, a shift in mitochondrial dynamics was indicated by increased MF1 expression and decreased FIS1 expression. These data suggest that EHDPP disrupts adrenal steroidogenesis and lipid homeostasis, emphasizing its potential endocrine-disrupting effects.

PMID:40178524 | DOI:10.1021/acs.chemrestox.5c00030

Environ Sci Technol. 2025 Apr 3. doi: 10.1021/acs.est.4c10565. Online ahead of print.

ABSTRACT

Sodium p-perfluorous nonenoxybenzenesulfonate (OBS) as a novel surrogate for perfluorooctanesulfonate (PFOS) has been extensively utilized in industrial manufacturing and daily life. However, studies on OBS-induced environmental health risks of obstructive biosynthesis (OBS) are currently limited, particularly the risk for thyroid diseases. Following the construction of in vivo (mouse) and in vitro (normal human primary thyrocytes) models of subchronic low-dose OBS exposure, we explored the thyroid-disrupting effects of OBS through multiomics approaches and experimental validations. Our results showed that subchronic exposure to low doses of OBS led to primary hypothyroidism in mice, presenting with reduced number and functional abnormalities of thyrocytes. Further in vitro assays confirmed that low-dose OBS-induced disulfidptosis, a newly discovered form of programmed cell death, in human primary thyrocytes. Meanwhile, exposure to low-dose OBS remarkably suppressed thyroid hormone synthesis pathways in mouse and human thyrocytes. The charted multiomic landscape of OBS-induced primary hypothyroidism in mammals revealed the thyroid toxicity and endocrine-disrupting properties of OBS, suggesting that it is not a safe alternative to PFOS.

PMID:40178189 | DOI:10.1021/acs.est.4c10565

Dalton Trans. 2025 Apr 2. doi: 10.1039/d5dt00154d. Online ahead of print.

ABSTRACT

The hybrid bentonite/ZnO composites based on the metal-organic framework (MOF) ZIF-8 were synthesized by a microwave method using 2-methylimidazole and zinc nitrate, and incorporating natural bentonite (5, 15, and 25 wt%) followed by thermal treatment at 550 °C. The as-prepared materials were characterized for their crystal structure, morphology, composition, surface chemical states, textural and optical properties. The photocatalytic activity of the ZnO/bentonite composites was evaluated in the degradation of a mixture solution of endocrine disruptors (EDCs) (bisphenol A, propylparaben, and 17α-ethinylestradiol, 5 mg L^-1 each) at pH = 7 under simulated solar light. The material characterization showed that incorporating bentonite into ZnO increased the specific surface area, facilitated the formation of oxygen vacancies, and decreased the recombination rate of e^-/h⁺ pairs compared to ZnO. The solar photocatalytic activity revealed that bentonite 15 wt%/ZIF-8 derived ZnO composite showed enhanced photocatalytic activity compared to ZIF-8 derived ZnO, allowing the total degradation and 61.26% mineralization of the EDC mixture in 240 min. Furthermore, the effluent showed a decrease in estrogenic activity by the end of the photocatalytic process, with no by-products formed that present estrogenic activity. The bentonite/ZIF-8 derived ZnO composite is proposed as an alternative ZnO-based catalyst that effectively removes the EDC compounds from aqueous media.

PMID:40171614 | DOI:10.1039/d5dt00154d

Front Endocrinol (Lausanne). 2025 Mar 18;16:1529703. doi: 10.3389/fendo.2025.1529703. eCollection 2025.

ABSTRACT

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder affecting reproductive-age women, characterized primarily by hyperandrogenism, ovulatory dysfunction, and metabolic abnormalities. In recent years, the gut microbiota has garnered widespread attention for its potential role as a key regulator of host metabolism in the pathogenesis of PCOS. Studies have shown that PCOS patients exhibit dysbiosis in their gut microbiota, characterized by reduced microbial diversity, an imbalance in the ratio of Firmicutes to Bacteroidetes, changes in the abundance of specific taxa, and abnormal levels of metabolic products. These alterations may exacerbate metabolic dysfunction in PCOS through multiple mechanisms, including influencing host energy metabolism, disrupting lipid and bile acid metabolism, and inducing chronic inflammation. Addressing gut dysbiosis through the modulation of patients' microbiomes-such the use of, prebiotics, fecal microbiota transplantation, and optimizing diet lifestyle-may offer strategies for improving metabolic abnormalities and alleviating clinical symptoms in PCOS. Additionally, the gut microbiome promises as a potential marker, aiding in the precise diagnosis and personalization of PCOS. Although our current understanding of how the gut microbiota influences PCOS is still limited, research is needed to explore the causal relationships and mechanisms involved, providing a more reliable theoretical basis for clinical. This review aims summarize the research progress on the relationship between gut microbiota and PCOS, and to suggest future directions to promote the development of prevention and treatment strategies for PCOS.

PMID:40171188 | PMC:PMC11958223 | DOI:10.3389/fendo.2025.1529703

Chemosphere. 2025 Apr 1;377:144339. doi: 10.1016/j.chemosphere.2025.144339. Online ahead of print.

ABSTRACT

Organochlorine pesticides (OCPs) were extensively used in India in agriculture as insecticides and in public health programs to control vector borne diseases like Malaria, and typhus. This rampant use led OCPs to persist in the environment due to their resistance to natural degradation and biotransformation, consequently, enter the human body through the food chain and bio-accumulate in adipose tissue as they are lipophillic. Exposure to OCPs have been linked to various diseases due to their endocrine disrupting properties, and lipophillic nature. The purpose of the study is to estimate the OCPs level in the breast cancer patients, and to compare the OCP levels within breast cancer patients based on their clinical features. A case control study was conducted on 100 breast cancer cases and 100 controls of benign breast disease patients. Quantification of OCPs was done by Gas Chromatography system equipped with 63 Ni Electron Capture Detector. Significantly higher levels of γHCH, Endosulfan-II, p'p'DDT and o'p'DDT were found in cases with respect to controls (p < 0.05). The odds ratios (ORs) show a significant association of Endosulfan-II (1.3) and p'p'DDT (2.7) levels with risk of breast cancer. Further, significantly higher levels of γHCH, p'p'DDT and Endosulfan-II were found in lymph node metastasis cases and γHCH and pp'DDD in advanced tumor stage cases as compared to the cases without lymph node involvement, and early tumor stage respectively. The findings of the present study support the contribution of OCPs in the pathophysiology of breast cancer. Further, OCPs like p'p'DDT, Endosulfan-II, and γHCH may promote the progression of breast cancer by influencing the metastatic ability through lymphatic pathway.

PMID:40174388 | DOI:10.1016/j.chemosphere.2025.144339

Toxicol Rep. 2025 Mar 12;14:101988. doi: 10.1016/j.toxrep.2025.101988. eCollection 2025 Jun.

ABSTRACT

BACKGROUND: Methoxychlor (MXC), a widely used pesticide, poses significant toxicological risks to various biological systems. It is an environmental contaminant and the only organochlorine pesticide still using instead of DDT. Endocrine disruption of MXC is also under investigation.This study aimed to investigate the effects of MXC on antioxidant status, lipid peroxidation, and liver metabolism in experimental rats.

METHODS: Male Wistar rats were divided into control and treatment groups, with the latter receiving 150 mg/kg and 250 mg/kg body weight (BW) of MXC via oral administration for 30 days. Liver function was assessed by measuring circulating biomarkers, including Alanine Transaminase (ALT), Aspartate Transaminase (AST), and Alkaline Phosphatase (ALP). Oxidative damage was evaluated by determining Thiobarbituric Acid Reactive Substances (TBARS), hydroperoxide (HYP), and other lipid peroxidation markers. Key enzymes involved in antioxidant defense mechanisms were also analyzed in the liver of experimental animals.

RESULTS: Our results demonstrated a significant increase in ALT, AST, and ALP levels in the serum of rats exposed to MXC, indicating impaired liver function. This was accompanied by elevated lipid peroxidation, further emphasizing oxidative stress. Moreover, the activities of antioxidant enzymes such as SOD, GPx, and CAT were markedly reduced in the MXC-exposed groups compared to the controls, suggesting a compromised antioxidant defense system.

CONCLUSION: These findings suggest that methoxychlor exposure disrupts liver function and induces oxidative stress by enhancing lipid peroxidation, thereby depleting natural antioxidant defenses. This study highlights the potential hepatotoxic effects of methoxychlor and underscores the role of oxidative stress in mediating its toxicity.

PMID:40170797 | PMC:PMC11960667 | DOI:10.1016/j.toxrep.2025.101988

Sci Rep. 2025 Apr 2;15(1):11244. doi: 10.1038/s41598-025-95996-7.

ABSTRACT

Endocrine-disrupting chemicals (EDCs) in the aquatic environment are an emerging concern and can lead to adverse health effects on humans and aquatic life. EDCsare ubiquitous in several daily use and personal care products and ubiquitous in aquatic ecosystems. The aquatic ecosystems also serve as major sinks of EDCs and have even been found to accumulate in aquatic organisms. Fish are an important sentinel species in the aquatic system and are a reliable indication of environmental water pollution. In the present study, we have assessed the immunotoxicity effects of three important EDCs, i.e., triclosan (TCS), bisphenol A (BPA), and diethyl phthalate (DEP). There is mounting evidence that EDCs impact several physiological systems, including fish immune systems. Hence, to better understand the immune system's complexity, we have investigated how EDCs alter the immune responses and can aggravate immunotoxicity using Labeo catla as a model fish species. The results showed significant upregulation of immune gene expression; exposure to EDCs differentially modulates immunity across the different organs (liver and brain) of Labeo catla. The present study highlighted that endocrine-disrupting compounds (TCS, BPA, and DEP) have a significant immunotoxicity effect in fish and activate several immunological pathways to control the toxic effect and maintain homeostasis. The results also indicate that immune genes can be used as a biomarker for EDC toxicity. However, further studies need to see how immune-disrupting effects happen at actual exposure levels in the environment to EDCs.

PMID:40175507 | DOI:10.1038/s41598-025-95996-7

Comp Biochem Physiol C Toxicol Pharmacol. 2025 Mar 31:110198. doi: 10.1016/j.cbpc.2025.110198. Online ahead of print.

ABSTRACT

Antimony (Sb) is an estrogenic metal. Exogenous exposure to Sb can affect estrogen levels and their receptor expression in organisms, exerting estrogen-disrupting effects and even inducing polycystic ovary syndrome (PCOS), which is accompanied by the progression of ovarian fibrosis. To investigate the pathological mechanism of this reproductive damage caused by Sb exposure, we exposed female zebrafish to Sb solution for 18 days for acute toxicity experiments. The results showed that Sb exposure affected the changes of GnRH, FSH, LH, E2 and T levels on the HPG axis, which disrupted the balance of sex steroid hormones in the internal environment of zebrafish and progression of PCOS. Furthermore, Sirius red staining revealed significant fibrosis in the ovarian tissues of Sb-exposed female zebrafish. This study adopted transcriptome sequencing and Western Blotting to explore the mechanisms of action. The biological processes and signaling pathways potentially associated with Sb-induced ovarian fibrosis were predicted by using GO annotation and KEGG pathway enrichment analysis, such as ECM receptors, TGF-β/Smad and WNT/β-catenin. The experiment results showed that Sb induced up-regulation of the transcription levels of the pro-fibrotic factors tgf-β3, wnt10a, ctnnb1, and β-catenin protein expression, suggesting the activation of the WNT/β-catenin pathways and TGF-β/Smad. Sb exposure led to up-regulation of ECM-related genes col2a1a, itgb1b.2, lamc1, fn1a and up-regulation of fibrosis markers α-SMA, Fn1a, col4a2 protein expression, Therefore, we hypothesized that Sb exposure activates the TGF-β/Smad and WNT/β-catenin pathways, leading to abnormal ECM deposition and promoting the progression of ovarian fibrosis in zebrafish.

PMID:40174734 | DOI:10.1016/j.cbpc.2025.110198

Hum Exp Toxicol. 2025 Jan-Dec;44:9603271251332255. doi: 10.1177/09603271251332255. Epub 2025 Apr 1.

ABSTRACT

IntroductionSodium dodecyl sulfate (SDS), a widely used surfactant in detergents, has raised concerns due to its potential health risks, particularly in children. This study evaluates the impact of SDS exposure on GH secretion in GH3 cells, focusing on oxidative stress as a key mechanism.MethodsGH3 cells were treated with varying concentrations of SDS (0.001-10 mM) for 24 or 48 h. Cell viability was assessed using the MTT assay, while GH secretion was quantified via ELISA. Oxidative stress levels were evaluated through ROS fluorescence assays, and gene expression of Nrf2, IL-6, TNF-α, and caspase-3 was analyzed using qPCR. Additionally, the antioxidant N-acetylcysteine (NAC) was used to determine its protective effects against SDS-induced oxidative stress.ResultsSDS exposure led to a dose-dependent decrease in GH secretion and cell viability, with oxidative stress identified as a primary driver. Nrf2 exhibited a biphasic response, showing transient upregulation at low doses but suppression at higher concentrations, exacerbating oxidative damage. NAC treatment reduced ROS levels and partially restored GH secretion, confirming the role of oxidative stress in SDS-induced toxicity.DiscussionThese findings suggest that SDS exposure may disrupt endocrine function, warranting further risk assessment of its safety in consumer products. Given SDS's prevalence in household products, future research should focus on the long-term effects of SDS exposure to children and potential therapeutic interventions to mitigate oxidative damage.

PMID:40170426 | DOI:10.1177/09603271251332255

Langmuir. 2025 Apr 2. doi: 10.1021/acs.langmuir.5c00534. Online ahead of print.

ABSTRACT

Bisphenol A (BPA) is extensively utilized as an industrial chemical in the production of certain plastics and epoxy resins. They are frequently found in environmental water and have the potential to cause risks to both the environment and human health. To efficiently remove the endocrine disruptor BPA from aqueous solutions, sea urchin-like magnetic material Fe₃O₄@PDA@NH₂-MIL-101 (Fe) was synthesized via hydrothermal methods. Fe₃O₄@PDA@NH₂-MIL-101 (Fe) has excellent adsorption performance, with a theoretical maximum adsorption capacity of 300.47 mg/g for BPA. The adsorption kinetics of BPA by Fe₃O₄@PDA@NH₂-MIL-101 (Fe) followed the pseudo-second-order kinetic model and Liu's isotherm model. Magnetic separation experiments reveal a high recovery efficiency, maintaining 94.82% of its initial adsorption capacity after five cycles. The primary adsorption mechanisms of Fe₃O₄@PDA@NH₂-MIL-101 (Fe) on BPA included pore filling, hydrogen bonding, π-π interaction, and Lewis acid-base interaction. Additionally, the material showed excellent removal performance of BPA, with a maximum adsorbed amount of 135.27 mg/g for total organic carbon (TOC) in the shale gas fracturing flowback fluid. These findings suggest that Fe₃O₄@PDA@NH₂-MIL-101 (Fe) holds significant potential as an adsorbent for BPA removal from actual wastewater, offering promising prospects for practical applications.

PMID:40170607 | DOI:10.1021/acs.langmuir.5c00534

Bull Environ Contam Toxicol. 2025 Apr 1;114(4):58. doi: 10.1007/s00128-025-04031-y.

ABSTRACT

Tin, a heavy metal, in trace amounts is believed to play various roles in the biological development of fish, including involvement in cell structure, enzyme activities, and the metabolism of proteins and carbohydrates. Two endocrine-disrupting chemicals, Tributyltin (TBT) and Triphenyltin (TPT), are prevalent in aquatic environments. This study examines the bioaccumulation of these compounds and their impact on oxidative stress enzymes. Zebrafish embryos were used to assess the acute toxicity of TBT, TPT, and SnCl₂. Toxicity tests were conducted on fertilized eggs using different concentrations of TBT, TPT, and SnCl₂ (0, 1, 5, 10, 15, and 20 ng/L). The LC_{50, 96 h} values for TBT, TPT, and SnCl₂ in zebrafish embryos were 4.2, 8.7, and 12.56 ng/L, respectively. The study found an increase in the catalase (CAT) superoxide dismutase (SOD), and malondialdehyde (MDA) for TBT, TPT, and SnCl₂. Moreover, TBT showed higher bioaccumulation than other compounds. The mortality rate was higher in embryos exposed to TBT, suggesting that embryos are more susceptible to TBT and can induce oxidative stress and disrupt the antioxidant equilibrium..

PMID:40167579 | DOI:10.1007/s00128-025-04031-y

Arch Argent Pediatr. 2025 Apr 3:e202410501. doi: 10.5546/aap.2024-10501.eng. Online ahead of print.

ABSTRACT

Introduction. Idiopathic premature thelarche (IPT) is defined as breast growth in girls before age 8 without activation of the gonadotrophic axis. Among the probable etiologies, endocrine disruptors (ED) with estrogenic action have been suggested. Objective. To evaluate whether there is an association between exposure and degree of exposure to the main EDs with estrogenic action in our environment and the development of IPT. Population and methods. Structured survey of caregivers of girls aged 3 to 8 years diagnosed with IPT and controls. The exposure evaluated included different EDs: bisphenol A (BPA), phytoestrogens, phthalates, and parabens, considering the degree of exposure according to weekly frequency. Results. Caregivers of 50 cases (7.2±1.3 years) and 48 controls (6.7±1.5 years) were interviewed. An association was found between IPT and exposure to phytoestrogens in food (OR: 14.6; 95%CI 1.8-118; p<0.01), the use of BPA containers exposed to temperature changes (OR 2.6; 95%CI 1.1-6.5; p<0.05), contact with phthalates (OR 2.9; 95%CI 1.2-7.5; p<0.05) and parabens (OR 2.7; 95%CI 1.2-6,1; p<0.05). In all the detailed EDs, we also found an association of IPT according to their degree of exposure. Conclusions. Exposure and degree of exposure to different sources of phytoestrogens, BPA, parabens, and phthalates were associated with the development of IPT.

PMID:40168507 | DOI:10.5546/aap.2024-10501.eng

Nanoscale Adv. 2025 Mar 12. doi: 10.1039/d4na01065e. Online ahead of print.

ABSTRACT

A highly effective and unique AgBr-NiO binary heterojunction was developed using an effective one-pot sol-gel method. The physicochemical properties of the produced materials were carefully examined using analytical techniques, including X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray (EDX) analysis, transmission electron microscopy (TEM), Brunauer-Emmett-Teller (BET), ultraviolet-visible diffuse reflectance spectroscopy (UV-vis-DRS), Fourier transform infrared spectroscopy (FTIR), and photoluminescence (PL). The mesoporous nature and high surface properties of AgBr-NiO were revealed by the BET analysis. The AgBr-NiO composite showed greater photocatalytic degradation efficiency than bare AgBr and NiO when exposed to visible light for the colored anionic dye rhodamine B (RhB) and bisphenol A (BPA), a colorless endocrine-disrupting contaminant (EDC), resulting in high photocatalytic activity for the degradation of RhB (97.6% in 11 min) and BPA (85% in 120 min). Additionally, a notable decrease in TOC over time was observed under similar reaction conditions in the photo-mineralization examination of both model pollutants. Trapping tests were conducted to determine which reactive oxygen species (ROS) were involved in the degradation process. A plausible Z-scheme mechanism for this n-p heterojunction was proposed to explain the formation of e^-/h⁺ pairs induced by visible light. The proposed work facilitates the development of a recyclable photocatalyst characterized by high biological activity and low toxicity.

PMID:40160255 | PMC:PMC11949248 | DOI:10.1039/d4na01065e

bioRxiv [Preprint]. 2025 Mar 12:2025.03.07.642104. doi: 10.1101/2025.03.07.642104.

ABSTRACT

Glucocorticoids are steroid hormones that regulate stress homeostasis, metabolism, and inflammatory responses. Dysregulation of the glucocorticoid receptor (GR) is linked to diseases such as obesity, mood disorders, and immune dysfunction. Endocrine-disrupting chemicals (EDCs) are widespread environmental contaminants known to interfere with hormone signaling, but their impact on glucocorticoid signaling remains unclear. While several GR-disrupting compounds have been identified in vitro , their in vivo effects remain largely unknown. In this study, we identified the agricultural agents dichlorodiphenyltrichloroethane (DDT) and ziram as GR-disruptors in vitro. In vivo , corticosterone co-treatment with DDT or the GR antagonist RU-486 inhibited the expression of classic GR-regulated transcripts in the liver. Furthermore, chronic exposure to DDT or RU-486 significantly reduced circulating B and T lymphocyte populations, respectively. These findings underscore the need to translate in vitro discoveries into in vivo models to assess the clinical relevance of GR-disrupting compounds. Moreover, they highlight the potential for xenobiotic-induced GR disruption to impair metabolic and immune homeostasis, potentially increasing disease susceptibility.

PMID:40161699 | PMC:PMC11952347 | DOI:10.1101/2025.03.07.642104

Front Reprod Health. 2025 Mar 14;7:1519896. doi: 10.3389/frph.2025.1519896. eCollection 2025.

ABSTRACT

INTRODUCTION: Recently, issues related to climate change and endocrine-disrupting chemicals have come to the forefront. In particular, the pursuit of convenience has led to increased exposure to endocrine-disrupting chemicals in daily life, posing threats to reproductive health, including infertility and cancer. Therefore, this study aims to develop a questionnaire to assess the reproductive health behaviors of Koreans for reducing exposure to endocrine-disrupting chemicals, and to verify its reliability and validity.

MATERIALS AND METHOD: This methodological study involved 288 adult men and women in South Korea and conducted item analysis, exploratory factor analysis, and confirmatory factor analysis.

RESULTS: The developed survey questionnaire consists of four factors and 19 detailed items related to reproductive health behaviors and reproductive health promotion behaviors through the main exposure routes of endocrine-disrupting chemicals: food, respiratory pathways, and skin absorption.

CONCLUSION: Based on the results of this study, it is hoped that research on reproductive health behaviors aimed at reducing EDC exposure will expand, considering various environments such as national and ethnic differences.

PMID:40162030 | PMC:PMC11949970 | DOI:10.3389/frph.2025.1519896

Environ Health Perspect. 2025 Mar 31. doi: 10.1289/EHP15547. Online ahead of print.

ABSTRACT

BACKGROUND: Pregnant women are exposed to numerous endocrine disrupting chemicals (EDCs). Pregnancy-related nausea likely has hormonal etiology and may persist beyond the first trimester.

OBJECTIVES: Therefore, we aimed to determine the relationship between EDC biomarkers and pregnancy nausea characteristics.

METHODS: Illinois Kids Development Study (I-KIDS) pregnant women (n=467) reported nausea symptoms monthly from conception to delivery. We categorized women as never having nausea (9%), or as having typical (ends by 17 weeks gestation; 42%), persistent (ends after 17 weeks gestation; 25%), or irregular (24%) nausea. Women provided five urine samples across pregnancy, which we pooled and analyzed for phthalate/replacement, phenol, and triclocarban biomarkers. Using covariate-adjusted logistic regression, we evaluated relationships of EDCs with nausea and used quantile-based g-computation (QGComp) and Bayesian kernel machine regression (BKMR) to evaluate joint associations of EDCs with nausea symptoms. We also considered differences in associations by fetal sex.

RESULTS: Only the sum of urinary biomarkers of di(isononyl) cyclohexane-1,2-dicarboxylate (ΣDiNCH) was associated with higher risk of persistent nausea compared to typical nausea (OR: 1.18; 95% CI: 1.01, 1.37) in all women. However, using QGComp, a 10% higher concentration of the EDC mixture was associated with 14% higher risk of persistent nausea (RR: 1.14; 95% CI:1.01,1.30), due to ΣDiNCH, ethylparaben, and the sum of di-2-ethylhexyl phthalate (ΣDEHP) metabolites. Similarly, using BMKR, the EDC mixture was associated with greater odds of persistent nausea in all women. In women carrying male offspring, ethylparaben was associated with persistent nausea, and a 10% higher concentration of the QGComp mixture was associated with 26% higher risk of persistent nausea (RR: 1.26; 95%CI:1.13,1.41), driven by ethylparaben and ΣDiNCH. Consistently, using BKMR, EDCs were positively associated with persistent nausea in women carrying males. We did not identify associations between EDC biomarkers and persistent nausea in women carrying females or between EDC biomarkers and other nausea patterns.

DISCUSSION: Non-persistent EDCs, modeled as a mixture, are associated with persistent nausea in pregnancy, primarily in women carrying males. Future work should explore possible mechanisms, clinical implications, and interventions to reduce exposures and symptoms. https://doi.org/10.1289/EHP15547.

PMID:40163373 | DOI:10.1289/EHP15547

Mar Pollut Bull. 2025 Mar 29;215:117896. doi: 10.1016/j.marpolbul.2025.117896. Online ahead of print.

ABSTRACT

The presence of endocrine-disrupting chemicals (EDCs) in aquatic food systems presents significant health risks for consumers, highlighting the need for advanced monitoring and remediation solutions. This study provides a comprehensive characterization of the hazards posed by EDCs in the Vembanad Estuary (VE) of India through the biomonitoring of black clams (Villorita cyprinoides), which serve as an indicator organism. Additionally, management strategies such as depuration and cooking were evaluated for their effectiveness in reducing human health risks associated with exposure to these identified EDCs. Comprehensive screening identified 85 potential EDCs, including polycyclic aromatic hydrocarbons (PAH - 64.0 %) and organochlorine pesticides (OCPs - 13.1 %). The concentration ranges for these contaminants were 5.01-225.00 ng/g and 5.05-58.92 ng/g, respectively. Depuration was achieved using a multi-tank depuration system designed and installed in a coastal village to treat black clams harvested from the estuary as a sustainable management intervention. The depuration process significantly reduced the level of all pollutants to below the limit of quantification (LOQ), while cooking could only slightly reduce the mean concentration of PAHs from 23.67 ng/g to 17.33 ng/g. The human health risk assessment for the pre- and post-cooked clam samples revealed higher hazard index values (>1), indicating immediate risk of dietary exposure. Meanwhile, the depurated samples were safe after the complete removal of these EDCs. These findings highlight the necessity of proper environmental management practices in estuarine ecosystems that might reduce the contaminant loads in aquatic food sources, thereby ensuring both ecosystem conservation and human well-being.

PMID:40158437 | DOI:10.1016/j.marpolbul.2025.117896

J Hazard Mater. 2025 Mar 26;492:138067. doi: 10.1016/j.jhazmat.2025.138067. Online ahead of print.

ABSTRACT

Early-life exposure to endocrine-disrupting chemicals (EDCs) may contribute to small vulnerable newborns, including conditions such as being small for gestational age (SGA) and preterm birth (PTB), yet evidence remains limited. This study, which is based on 739 mother-infant pairs in the Chinese Jiashan Birth Cohort (2016-2018), including 39 SGA and 38 PTB cases, employed interpretable machine learning to elucidate the isolated effects of 34 EDCs on SGA and PTB risk and sex interactions in a multi-substance exposure context. Extra Trees and CatBoost classifiers performed best for SGA and PTB, respectively, achieving sensitivities of 0.60 and 0.73 and specificities of 0.82 and 0.97. For SGA, key predictors included bisphenol A (2,3-dihydroxypropyl) glycidyl ether (BADGE-H₂O), benzophenone (bZp), bisphenol A bis(2,3-dihydroxypropyl) ether (BADGE-2H₂O), propyl paraben (PrP), and 2-methylthio-benzothiazole (2-Me-S-BTH). Lower exposures to BADGE-H₂O, bZp, and BADGE-2H₂O (concentrations below 0.21, 4.22, and 0.93 μg·g^-1 creatinine, respectively) and higher exposure to 2-Me-S-BTH (above 0.15 μg·g^-1 creatinine) were both associated with increased SGA risk. Notably, BADGE-H₂O, BADGE-2H₂O, and PrP showed significant interactions with fetal sex. For PTB, key predictors included ethyl paraben (EtP), methyl paraben (MeP), bZp, BADGE-H₂O, and 1H-benzotriazole (1-H-BTR). Lower BADGE-H₂O and higher EtP and bZp exposures increased PTB risk (< 0.10 and > 0.01 and 0.60 μg·g^-1 creatinine, respectively). Male fetuses appeared more susceptible to EtP and MeP, and female fetuses were more susceptible to 1-H-BTR. Bayesian kernel machine regression was performed to compare the results. This study demonstrated the potential of interpretable machine learning in environmental epidemiology.

PMID:40158502 | DOI:10.1016/j.jhazmat.2025.138067

Int J Hyg Environ Health. 2025 Mar 29;266:114569. doi: 10.1016/j.ijheh.2025.114569. Online ahead of print.

ABSTRACT

BACKGROUND: Personal care products frequently contain endocrine disrupting chemicals (EDCs) including parabens and phthalates, which can alter glucose metabolism. The postpartum period is a time of rapid metabolic change, but whether EDC-associated product use impacts postpartum glucose metabolism is unknown.

METHODS: We included 270 participants from the Boston, MA-based Environmental Reproductive and Glucose Outcomes (ERGO) pregnancy cohort with data on self-reported personal care product use at ≤4 pregnancy visits (median: 11, 19, 26, 36 weeks of gestation) and 1 postpartum visit (median: 9 weeks). We quantified postpartum hemoglobin A1c (HbA1c), fasting insulin, fasting- and 2-h glucose post-75-g oral glucose tolerance test, and calculated homeostatic model assessment for insulin sensitivity (HOMA2-S) and beta-cell function (HOMA2-B). Using covariate-adjusted linear regression, we estimated visit-specific associations of product use with postpartum glycemic outcomes.

RESULTS: Associations of product use with postpartum glycemic measures were mixed. Users of certain hair products had lower postpartum insulin sensitivity compared to non-users (e.g., Visit1 hair gel/spray: 22.8% difference [95% CI: 39.2, -1.9] in mean HOMA2-S). Conversely, users of products like deodorant, liquid- and bar soap, had higher insulin sensitivity and lower glucose levels (e.g., postpartum deodorant: 32.1% difference [95% CI: 7.0, 63.1] in mean HOMA2-S; -3.1 mg/dL [95% CI: 6.3, -0.04] mean fasting glucose). Associations with other products were inconsistent across timepoints or null.

CONCLUSION: Use of certain personal care products during the perinatal period was associated with altered postpartum glucose metabolism. Larger studies are needed to understand the impacts of product use patterns on glycemic outcomes.

PMID:40158509 | DOI:10.1016/j.ijheh.2025.114569

Toxicol Lett. 2025 Mar 28:S0378-4274(25)00060-8. doi: 10.1016/j.toxlet.2025.03.011. Online ahead of print.

ABSTRACT

The organophosphorus pesticide chlorpyrifos (CPF) is widely utilized in agriculture to protect crops from pests and diseases. Concerns regarding its extensive use have emerged due to the substance's persistence, bioaccumulation, endocrine disruption, and associated toxicity, which may lead to various adverse reactions. In this study, 32 male C57BL/6J mice were orally administered varying doses of CPF over a period of two weeks. Metabolic perturbations resulting from subacute exposure to CPF were assessed using LC-MS/MS-based untargeted metabolomics, alongside biochemical analysis and histopathological techniques. The 16S rRNA gene sequencing method was employed to evaluate changes in the gut microbial community within the cecal contents of mice exposed to CPF. In vivo studies have shown that CPF exposure induced dose-dependent damage and dysregulation of the intestinal microbiota in mouse colonic tissues. This was characterized by significant alterations in the gut microbiota, increased intestinal permeability and elevated levels of lipopolysaccharides. These changes may have compromised intestinal barrier function and facilitated the transfer of intestinal microbial metabolites and endotoxins to the liver, subsequently leading to liver injury. Collectively, this study elucidates a potential mechanism by which CPF triggers liver injury through alterations in the intestinal microbial community and increased intestinal permeability. These findings not only enhance our understanding of the toxicological effects of CPF but also contribute to the assessment of health risks associated with CPF exposure.

PMID:40158758 | DOI:10.1016/j.toxlet.2025.03.011

Aquat Toxicol. 2025 Mar 25;283:107337. doi: 10.1016/j.aquatox.2025.107337. Online ahead of print.

ABSTRACT

Endocrine disruptors (EDs) can disrupt the gonadotropic axis, which consists of the Hypothalamus-Pituitary-Gonads (HPG), notably by altering aromatase (cyp19a), a key enzyme regulating the endocrine system and reproductive function in fish. The effects of EDs can be predicted by integrating both toxicokinetic (TK) and toxicodynamic (TD) processes in order to relate adverse outcomes to external exposures. In this study, we developed a physiologically based kinetic-toxicodynamic model to simulate the disruption of the HPG axis (PBK-TD, hereafter named PBK-HPG) in female zebrafish exposed to either of two aromatase inhibitors, imazalil or prochloraz. The model was calibrated using Bayesian methods and supported by novel experimental data, including measurements of vitellogenin, 17β-estradiol, and 11-ketotestosterone levels, along with in vivo monitoring of the cyp19a1a gene in transgenic cyp19a1a-GFP ebrafish. Seamless integration of a PBK model within a TD model of the HPG-axis, provided the link between external exposure and internal levels of imazalil and prochloraz in key organs, allowing for mechanistic predictions of their inhibitory effects on gonadal aromatase. Our PBK-HPG model accurately predicted both baseline homeostasis and the effects of aromatase inhibition, with all endocrine endpoints including reproductive disruption, i.e., decreased egg production, falling within a twofold range of both experimental and literature data. Therefore, our PBK-HPG model could further support the development of a mechanistic qAOP with TK considerations. The model offers significant potential for improving environmental risk assessments of EDs and possibly other stressors across species.

PMID:40158424 | DOI:10.1016/j.aquatox.2025.107337

Sci Rep. 2025 Mar 28;15(1):10752. doi: 10.1038/s41598-025-94902-5.

ABSTRACT

The study investigates the synergistic endocrine disruption and cellular toxicity resulting from co-exposure to polyethylene microplastics (PE-MPs) and bisphenol A (BPA) in zebrafish and MLTC-1 cells. Previous research has extensively examined the individual effects of PE-MPs and BPA on endocrine systems and cellular health. However, the specific interactions and combined toxicological impacts of these two common environmental pollutants remain underexplored, particularly in terms of their synergistic effects on endocrine pathways and cellular viability. To fill this knowledge gap, we characterized PE-MPs using scanning electron microscopy and Raman spectrometry and exposed MLTC-1 cells to PE-MPs, BPA, or combinations of both. The results showed that co-exposure to 100 µg/mL PE-MPs and 100-150 µmol/L BPA for 48 h significantly decreased cell viability, increased apoptosis rates, induced G2/M cell cycle arrest, reduced mitochondrial membrane potential, and altered the transcriptional expression of genes related to steroidogenesis. Specifically, co-exposure upregulated the Ar while downregulating Lhr and 3β-Hsd, with these effects being more pronounced than those observed with single exposures. In a complementary in vivo study, adult zebrafish were exposed to environmentally relevant concentrations of PE-MPs (1 mg/L) and BPA (1.5 µg/L) for 28 days. This co-exposure resulted in significant increases in the GSI and alterations in the gene expression associated with the HPG axis. In male zebrafish brains, genes such as Gnrh2, Esr1, and Ar were downregulated, while in female brains, Gnrh3, Esr1, and Ar also exhibited downregulation. In male testes, Star, Cyp11a1, and Hsd11b2 were upregulated, whereas Cyp19a1a, Hsd3b, Hsd20b, and Hsd17b3 were downregulated. In contrast, female ovaries showed upregulation of Cyp11a1, Cyp17, Cyp11b, Hsd3b, Hsd20b, and Hsd17b3, while Cyp19a1a was downregulated, indicating a sex-specific endocrine disruption. Overall, the findings reveal that co-exposure to PE-MPs and BPA induces synergistic toxic effects both in vitro and in vivo, which underscores the importance of studying the effects of combined pollutants to better assess environmental health risks.

PMID:40155689 | PMC:PMC11953243 | DOI:10.1038/s41598-025-94902-5

J Expo Sci Environ Epidemiol. 2025 Mar 29. doi: 10.1038/s41370-025-00768-0. Online ahead of print.

ABSTRACT

BACKGROUND: While recognition of airborne microplastics is increasing, there are still limited data on the microplastics within the aerosol size fractions most relevant to human inhalation (PM₁₀ and PM_2.5). Additionally, there are concerns that many of the additives used in plastic formulations have endocrine-disrupting properties, which could increase the hazards associated with microplastic exposure.

OBJECTIVE: To better understand the toxicological risks associated with airborne microplastics, more data are urgently needed on the mass concentrations of both microplastics and the related chemical additives in the air we breathe. Inhalation exposure to plastic-related species is currently uncertain in chemical laboratory workplaces.

METHODS: Using a Pyrolysis Gas Chromatography Mass Spectrometry (Pyr-GC/MS) based method, the airborne mass concentrations of both polymeric material and small molecule plastic additives were determined in inhalable air from two indoor locations. This method represents a fast, direct technique that can be used to better standardize airborne microplastic measurements.

RESULTS: The PM_2.5 and PM₁₀ concentrations of seven different polymers were determined, with average plastic concentrations of 0.51 μg m^-3 for the PM_2.5 samples and 1.14 µg m^-3 for the PM₁₀ samples. Polycarbonate, polyvinylchloride, and polyethylene had the highest airborne concentrations in the inhalable fraction of air. Simultaneously, the airborne concentrations of plastic additives were determined, with phthalate-based plasticizers having an average concentration of 334 ng m^-3 across all air samples.

IMPACT: Both microplastics and their chemical additives were quantified within the inhalable fraction of indoor air (PM₁₀), using a straight forward mass spectrometry technique with minimal sample preparation. This information furthers knowledge on the hazards associated with indoor air exposure, and it presents a useful methodology for the mass quantification of plastic-related airborne pollutants.

PMID:40158056 | DOI:10.1038/s41370-025-00768-0

Bioorg Chem. 2025 Mar 26;159:108415. doi: 10.1016/j.bioorg.2025.108415. Online ahead of print.

ABSTRACT

As a derivative of bisphenol A (BPA), bisphenol A glycidyl dimethacrylate (Bis-GMA) is questioned regarding its endocrine-disrupting properties. We previously reported a plant-derived monomer, betulin-based maleic diester derivative (MABet), as a substitute for Bis-GMA, but its yellow powdery appearance greatly affected the viscosity and aesthetics of dental resins. Herein, we synthesized three novel types of mPEG-functionalized MABet (P_nMABet) by leveraging the active carboxylic acid groups of MABet to undergo a DCC coupling reaction with mPEG variants with diverse repeating ethylene glycol units (n = 7, 12, and 16). Their chemical structures were validated using ¹H and ¹³C NMR spectroscopy, FT-IR spectroscopy, and HR-MS. Afterwards, the P_nMABet were incorporated into Bis-GMA-based resins at 10, 30, and 50 wt%. The mechanical performance was firstly evaluated to determine the optimal monomer content. The results showed that all P_nMABet monomers were light-yellow liquids. Increasing their concentration from 10, 30, to 50 wt% and the number of repeating units of mPEG from 7, 12, to 16 significantly reduced the mechanical property of resins. Of all groups, 10 wt% addition of P₇MABet endowed the resulting 1P₇M4B5T resin with the highest flexural and compressive strength (123.2 ± 10.3 MPa; 296.6 ± 27.5 MPa) than the 5B5T control (70.0 ± 6.4 MPa; 230.5 ± 22.5 MPa). This resin also exhibited comparable viscosity, polymerization conversion, cytotoxicity to 5B5T without antibacterial activity. The developed P_nMABet have the potential to modulate resin viscosity. Exploring the structure-property relationship is beneficial to realize monomer design and regulate resin properties.

PMID:40157012 | DOI:10.1016/j.bioorg.2025.108415

Sci Rep. 2025 Mar 28;15(1):10752. doi: 10.1038/s41598-025-94902-5.

ABSTRACT

The study investigates the synergistic endocrine disruption and cellular toxicity resulting from co-exposure to polyethylene microplastics (PE-MPs) and bisphenol A (BPA) in zebrafish and MLTC-1 cells. Previous research has extensively examined the individual effects of PE-MPs and BPA on endocrine systems and cellular health. However, the specific interactions and combined toxicological impacts of these two common environmental pollutants remain underexplored, particularly in terms of their synergistic effects on endocrine pathways and cellular viability. To fill this knowledge gap, we characterized PE-MPs using scanning electron microscopy and Raman spectrometry and exposed MLTC-1 cells to PE-MPs, BPA, or combinations of both. The results showed that co-exposure to 100 µg/mL PE-MPs and 100-150 µmol/L BPA for 48 h significantly decreased cell viability, increased apoptosis rates, induced G2/M cell cycle arrest, reduced mitochondrial membrane potential, and altered the transcriptional expression of genes related to steroidogenesis. Specifically, co-exposure upregulated the Ar while downregulating Lhr and 3β-Hsd, with these effects being more pronounced than those observed with single exposures. In a complementary in vivo study, adult zebrafish were exposed to environmentally relevant concentrations of PE-MPs (1 mg/L) and BPA (1.5 µg/L) for 28 days. This co-exposure resulted in significant increases in the GSI and alterations in the gene expression associated with the HPG axis. In male zebrafish brains, genes such as Gnrh2, Esr1, and Ar were downregulated, while in female brains, Gnrh3, Esr1, and Ar also exhibited downregulation. In male testes, Star, Cyp11a1, and Hsd11b2 were upregulated, whereas Cyp19a1a, Hsd3b, Hsd20b, and Hsd17b3 were downregulated. In contrast, female ovaries showed upregulation of Cyp11a1, Cyp17, Cyp11b, Hsd3b, Hsd20b, and Hsd17b3, while Cyp19a1a was downregulated, indicating a sex-specific endocrine disruption. Overall, the findings reveal that co-exposure to PE-MPs and BPA induces synergistic toxic effects both in vitro and in vivo, which underscores the importance of studying the effects of combined pollutants to better assess environmental health risks.

PMID:40155689 | PMC:PMC11953243 | DOI:10.1038/s41598-025-94902-5

Mar Pollut Bull. 2025 Mar 28;215:117866. doi: 10.1016/j.marpolbul.2025.117866. Online ahead of print.

ABSTRACT

Information regarding the sources, distribution and ecological implications of organic contaminants in the coral reef ecosystems is limited. Phthalic acid esters (PAEs) are toxic contaminants due to their endocrine-disrupting and carcinogenic properties. This study investigated the sources, distribution and ecological risk of PAEs (15 PAE congeners) in dissolved and particulate matter-bound forms present in the coral reefs of the Lakshadweep Archipelago. Samples (water and suspended particulate matter) collected from 24 stations of 4 coral islands (Perumal Par, Bangaram, Agatti and Kavaratti) during January and December 2022 were analysed for 15 PAE congeners. The concentration of PAEs was generally lower in coral reef waters than those reported worldwide. The dissolved PAEs (TDPAEs) ranged from 9.23 to 820.85 ng/L, and the particulate PAEs (TPPAEs) ranged from 642.90 to 28,315.45 ng/g. Principal component analysis (PCA) identified three major clusters: one cluster representing low molecular weight PAEs (cosmetic products), while the other two represented medium to high molecular weight PAEs (plastic products). The study region's risk quotient (RQ) values indicated a moderate to high ecological risk caused by di-isobutyl phthalate (DIBP) and di-n-butyl phthalate (DnBP) to crustaceans and fish and indirectly to human health. Therefore, this study strongly recommends regular, systematic monitoring and pollution assessment to avoid the environmental degradation of these fragile ecosystems. This baseline data on PAEs and their source apportionment can help develop mitigative measures for reducing organic contaminants in the coral reef environment.

PMID:40157213 | DOI:10.1016/j.marpolbul.2025.117866

Biochem Biophys Res Commun. 2025 Mar 22;760:151678. doi: 10.1016/j.bbrc.2025.151678. Online ahead of print.

ABSTRACT

Bisphenol A (BPA) is a well-known endocrine-disrupting chemical (EDC) that has been implicated in cancer development. However, the specific mechanisms of EDCs, including BPA, remain unclear. Voltage-gated potassium (Kv) channels have been closely related to cancer. In particular, Kv3.4 plays a role in cancer malignancy, including cell migration via the ERK and AKT signaling pathways. In this study, we investigated the mechanism of BPA in relation to Kv3.4 expression in human breast cancer MCF7 cells. BPA treatment significantly increased Kv3.4 expression at both the mRNA and protein levels and induced cell migration. Further analysis demonstrated that Kv3.4 is closely related to integrin β and integrin-regulated FAK signaling. However, BPA-induced cell migration and integrin-regulated FAK signaling were significantly abolished by Kv3.4 silencing. Therefore, we concluded that BPA is closely associated with cancer cell migration mediated by Kv3.4 via integrin-regulated FAK signaling. These findings provide novel insights into the role of BPA in cancer progression and suggest Kv3.4 as a potential therapeutic target for BPA-associated cell migration.

PMID:40157292 | DOI:10.1016/j.bbrc.2025.151678

Brain Res Bull. 2025 Mar 27;224:111324. doi: 10.1016/j.brainresbull.2025.111324. Online ahead of print.

ABSTRACT

OBJECTIVE: The hypothalamic-pituitary-thyroid axis has been well-known. However, whether follicular thyroid adenoma (FTA) could affect brain glucose metabolism is still unknown. Therefore, we explored the brain glucose metabolic characteristics of FTA with Fluorodeoxyglucose F18 positron emission tomography/magnetic resonance imaging.

METHODS: Totally 30 FTA patients without clinical symptoms (FTA group), and 60 age- and sex-matched healthy controls (HC group) were included and randomly divided into cohort A and B in 2:1 ratio. Cohort A was analyzed with scaled sub-profile model/principal component analysis (SSM/PCA) for pattern identification. Cohort B was calculated the individual scores to validate expression of the pattern. Then we calculated the metabolic connectivity based on characteristics of the pattern to investigate the underlying mechanism. Finally, we constructed metabolic brain networks and analyzed the topological properties to further explore the brain metabolic model.

RESULTS: In SSM/PCA, FTA group showed an almost global, left-right symmetrical pattern. In metabolic connectivity, FTA group showed increased metabolic connectivity in brain regions of the sensorimotor network, ventral default mode network (DMN), posterior salient network, right executive control network (ECN), visuospatial network and language network when compared to HC group, and showed decreased connectivity in dorsal DMN and left ECN. In topological properties of brain network, FTA group showed an increased betweenness centrality (BC) in left rolandic operculum, a decreased BC in superior temporal gyrus, increased BC and Degree in right precentral gyrus, increased D in right parahippocampal gyrus and left hippocampus, and decreased D and efficiency in right orbital part of middle frontal gyrus (FDR correction for multiple comparisons, P < 0.05).

CONCLUSION: Although FTA patients are not yet symptomatic, their brain metabolic characteristics include extensive brain alterations, disrupted internal connectivity, not only involving brain regions associated with endocrine activity, but also brain networks and regions associated with motor, emotion and cognition.

PMID:40157550 | DOI:10.1016/j.brainresbull.2025.111324

J Expo Sci Environ Epidemiol. 2025 Mar 29. doi: 10.1038/s41370-025-00768-0. Online ahead of print.

ABSTRACT

BACKGROUND: While recognition of airborne microplastics is increasing, there are still limited data on the microplastics within the aerosol size fractions most relevant to human inhalation (PM₁₀ and PM_2.5). Additionally, there are concerns that many of the additives used in plastic formulations have endocrine-disrupting properties, which could increase the hazards associated with microplastic exposure.

OBJECTIVE: To better understand the toxicological risks associated with airborne microplastics, more data are urgently needed on the mass concentrations of both microplastics and the related chemical additives in the air we breathe. Inhalation exposure to plastic-related species is currently uncertain in chemical laboratory workplaces.

METHODS: Using a Pyrolysis Gas Chromatography Mass Spectrometry (Pyr-GC/MS) based method, the airborne mass concentrations of both polymeric material and small molecule plastic additives were determined in inhalable air from two indoor locations. This method represents a fast, direct technique that can be used to better standardize airborne microplastic measurements.

RESULTS: The PM_2.5 and PM₁₀ concentrations of seven different polymers were determined, with average plastic concentrations of 0.51 μg m^-3 for the PM_2.5 samples and 1.14 µg m^-3 for the PM₁₀ samples. Polycarbonate, polyvinylchloride, and polyethylene had the highest airborne concentrations in the inhalable fraction of air. Simultaneously, the airborne concentrations of plastic additives were determined, with phthalate-based plasticizers having an average concentration of 334 ng m^-3 across all air samples.

IMPACT: Both microplastics and their chemical additives were quantified within the inhalable fraction of indoor air (PM₁₀), using a straight forward mass spectrometry technique with minimal sample preparation. This information furthers knowledge on the hazards associated with indoor air exposure, and it presents a useful methodology for the mass quantification of plastic-related airborne pollutants.

PMID:40158056 | DOI:10.1038/s41370-025-00768-0

Environ Health Perspect. 2025 Mar 28. doi: 10.1289/EHP15394. Online ahead of print.

ABSTRACT

BACKGROUND: Children's vulnerability to chemical toxicant exposures demands strong consideration of the chemical composition of products designed for and marketed toward them. Inadequacies in health-protective legislation and lack of mandatory ingredient disclosure in most children's products have created significant gaps in protection and oversight. Scientific literature can provide insight into the chemical constituency of children's products that may be useful for prioritizing future regulatory efforts.

OBJECTIVE: We aimed to present a proof of concept for applying systematic evidence mapping methodology to identify which chemicals of potential concern have been reported in the scientific literature to be present in products marketed toward children, to inform future research and regulatory efforts.

METHODS: We conducted a broad, all-encompassing survey of the available literature from four databases to identify chemicals present in children's products. Using systematic evidence mapping methodologies, we constructed a database of children's products and their chemical constituents (termed "product-chemical combinations") based on a broad survey of current and relevant environmental health literature. Our study focused on chemicals present on the California Safer Consumer Products Program's Candidate Chemicals List, which includes chemicals with one or more known hazard traits. We then conducted an exploratory data analysis of product category and product-chemical combination frequencies to identify common chemicals in specific products.

RESULTS: Our systematic evidence mapping identified 206 potentially hazardous chemicals in children's products, 170 of which were found in toys. In total, we found 1528 distinct product-chemical combinations; 582 product-chemical combinations included chemicals known to be hazardous or potentially hazardous. Ortho-phthalates in plastic toys, parabens in children's creams/lotions, and bisphenols in both baby bottles and teethers were the most frequently encountered product-chemical combinations of potential concern.

DISCUSSION: The frequently reported presence of endocrine-disrupting chemicals in multiple types of children's products raises concerns for aggregate exposures and reveals gaps in regulatory protections for this sensitive subpopulation. Our reproducible and systematic evidence-based approach serves as a case study that can guide other prioritization efforts for transparent regulatory action aimed at improving the safety of chemicals in consumer products. https://doi.org/10.1289/EHP15394.

PMID:40152882 | DOI:10.1289/EHP15394

Environ Sci Technol. 2025 Mar 28. doi: 10.1021/acs.est.4c12683. Online ahead of print.

ABSTRACT

The extensive application of isothiazolinones has led to widespread pollution and poses a threat to ecological health, creating a need for the development of green alternatives. With the objective of devising chemical design strategies, we initially explored the structure-activity relationship (SAR) and structure-toxicity relationship (STR) of isothiazolinones. By comparing the antimicrobial activities of commercial isothiazolinone analogues, chlorine substitutions were identified as key determinants of pathogen growth inhibition potency. The variability of reproductive endocrine-disrupting toxicity was primarily driven by the length of the alkyl carbon chain, based on interactions with molecular initiating events and disturbances in sex hormones. Inspired by the SAR and STR guidelines, two new isothiazolinones (i.e., Target 1 and Target 2) were designed and synthesized. Compared to the commercial analogue dichloro-octylisothiazolinone, Target 1, which has a shorter alkyl chain and the same chlorine count, demonstrated slightly stronger antimicrobial activity, significantly lower endocrine-disrupting toxicity, and longer environmental persistence. Meanwhile, Target 2, containing ether bonds within a shorter alkyl chain and the same chlorine count, exhibited weaker antimicrobial activity, significantly lower endocrine-disrupting toxicity, and slightly longer environmental persistence. Overall, this study proposes a mechanism-driven design strategy for isothiazolinone alternatives that successfully reduces endocrine toxicity while maintaining antimicrobial activity.

PMID:40153699 | DOI:10.1021/acs.est.4c12683

Chemosphere. 2025 Mar 27;377:144354. doi: 10.1016/j.chemosphere.2025.144354. Online ahead of print.

ABSTRACT

Polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCDD) are persistent organic pollutants (POPs) banned under the Stockholm Convention due to their severe health effects, including endocrine disruption, neurodevelopmental problems, and cancer. Historically used in electrical and electronic equipment (EEE), vehicles, furniture, and building materials, these chemicals persist in recycled plastics and have been found in children's products. Our scoping review synthesized emerging literature to assess the extent of these chemicals in children's products. Of 799 initial results, 28 studies met our inclusion criteria after removing duplicates and excluding those that met exclusion criteria. The 28 studies revealed widespread presence of legacy PBDEs and HBCDD in plastic childcare products and toys, including toys embedded in chocolates, often at concentrations exceeding the Basel Convention's low POP content limits. This widespread contamination stems from weak regulation of recycling practices in the circular economy, the use of recycled and potentially contaminated virgin plastics, and the absence of specific standards for POP-BFRs content in recycled plastics and children's products. Children's unique vulnerabilities make this issue critical. Global actions are, therefore, needed to address this problem. The Basel Convention should adopt stricter POP content limits to prevent the recycling of plastics with high PBDEs and HBCDD levels. Both the Stockholm and Basel Conventions should establish safe limits for these chemicals in recycled plastics and ban contaminated recycled plastics in children's products to ensure a safer circular economy. Future research should apply a lifecycle approach to identify and mitigate all sources of legacy PBDEs and HBCDD in children's products.

PMID:40153990 | DOI:10.1016/j.chemosphere.2025.144354

Reprod Sci. 2025 Mar 27. doi: 10.1007/s43032-025-01845-3. Online ahead of print.

ABSTRACT

Bisphenol A (BPA) is an environmental pollutant known to induce oxidative stress and reproductive toxicity, symptoms that are commonly associated with Polycystic Ovary Syndrome (PCOS). This study investigates the potential protective effects of Apigenin (AGN), a bioactive flavonoid, against BPA-induced PCOS-like symptoms in adult zebrafish. The research aims to explore the therapeutic potential of natural compounds in mitigating the effects of environmental endocrine disruptors. Zebrafish were exposed to BPA at a concentration of 10 µg/L, a level known to adversely affect aquatic organisms. The non-toxicity and efficacy of AGN were assessed through a dose-response study involving concentrations of 5, 10, 15, and 20 µM. The experimental design was informed by computational molecular dynamics, including docking and simulations targeting the human androgen receptor. The study involved histological staining of ovarian tissues, biochemical assays for antioxidant enzyme activities, high-performance liquid chromatography (HPLC) for BPA accumulation, and gene expression analysis targeting PCOS-susceptible genes. AGN treatment significantly modulated antioxidant defenses in zebrafish, restoring activities of enzymes such as superoxide dismutase (SOD) and catalase (CAT), and reducing lactate dehydrogenase (LDH) levels. Histologically, AGN mitigated follicular damage and prevented excessive collagen deposition and ovarian hypertrophy, with the gonadosomatic index (GSI) approaching control levels. HPLC analysis confirmed lower BPA accumulation in tissues of AGN-treated groups. Additionally, gene expression studies showed downregulation of PCOS-related genes and TNF-α. AGN exerts a protective role against BPA-induced reproductive toxicity and offers potential as a natural intervention for both ecological and reproductive health challenges.

PMID:40148704 | DOI:10.1007/s43032-025-01845-3

Biomolecules. 2025 Feb 20;15(3):312. doi: 10.3390/biom15030312.

ABSTRACT

Molecular biomarker profiling is an emerging field in maternal-fetal health with the potential to transform early detection and prediction of placental dysfunction. By analysing a range of biomarkers in maternal blood, researchers and clinicians can gain crucial insights into placental health, enabling timely interventions to enhance fetal and maternal outcomes. Placental structural function is vital for fetal growth and development, and disruptions can lead to serious pregnancy complications like preeclampsia. While conventional methods such as ultrasound and Doppler velocimetry offer valuable information on fetal growth and blood flow, they have limitations in predicting placental dysfunction before clinical signs manifest. In contrast, molecular biomarker profiling can provide a more comprehensive assessment by measuring proteins, metabolites, and microRNAs (miRNAs) in maternal blood, reflecting the placenta's endocrine and metabolic functions. This approach offers a deeper understanding of placental health and function, aiding in early detection and prediction of complications. Challenges in developing molecular biomarker profiling include pinpointing specific molecular changes in the placenta linked to pathologies, timing predictions of conditions before clinical onset, and understanding how placental dysfunction affects maternal metabolism. Validating specific biomarkers and integrating them effectively into clinical practice requires further research. This review underscores the significance of molecular biomarker profiling as a powerful tool for early detection and prediction of placental dysfunction in maternal-fetal health. Through an exploration of biomarker analysis, we delve into how a deeper understanding of placental health can potentially improve outcomes for both mother and baby. Furthermore, we address the critical need to validate the utility of biomarkers and effectively integrate them into clinical practice.

PMID:40149848 | PMC:PMC11940122 | DOI:10.3390/biom15030312

Chemosphere. 2025 Mar 27;377:144354. doi: 10.1016/j.chemosphere.2025.144354. Online ahead of print.

ABSTRACT

Polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCDD) are persistent organic pollutants (POPs) banned under the Stockholm Convention due to their severe health effects, including endocrine disruption, neurodevelopmental problems, and cancer. Historically used in electrical and electronic equipment (EEE), vehicles, furniture, and building materials, these chemicals persist in recycled plastics and have been found in children's products. Our scoping review synthesized emerging literature to assess the extent of these chemicals in children's products. Of 799 initial results, 28 studies met our inclusion criteria after removing duplicates and excluding those that met exclusion criteria. The 28 studies revealed widespread presence of legacy PBDEs and HBCDD in plastic childcare products and toys, including toys embedded in chocolates, often at concentrations exceeding the Basel Convention's low POP content limits. This widespread contamination stems from weak regulation of recycling practices in the circular economy, the use of recycled and potentially contaminated virgin plastics, and the absence of specific standards for POP-BFRs content in recycled plastics and children's products. Children's unique vulnerabilities make this issue critical. Global actions are, therefore, needed to address this problem. The Basel Convention should adopt stricter POP content limits to prevent the recycling of plastics with high PBDEs and HBCDD levels. Both the Stockholm and Basel Conventions should establish safe limits for these chemicals in recycled plastics and ban contaminated recycled plastics in children's products to ensure a safer circular economy. Future research should apply a lifecycle approach to identify and mitigate all sources of legacy PBDEs and HBCDD in children's products.

PMID:40153990 | DOI:10.1016/j.chemosphere.2025.144354

Front Toxicol. 2025 Mar 13;7:1442801. doi: 10.3389/ftox.2025.1442801. eCollection 2025.

ABSTRACT

The benefits of pesticides in enhancing agricultural yields are widely accepted by the general public. However, it is essential to address the limitations of the current agricultural model to develop more sustainable practices that prioritize environmental and human health. Brazil, a major global agricultural player, ranks among the top five agro-food producers and exporters, making it one of the largest consumers of pesticides worldwide. Notably, approximately 30% of pesticides used in Brazil are banned in the European Union. Paradoxically, some of these banned agrochemicals re-enter Northern markets through imported agro-food products. Addressing the regulatory disparities between Northern and Southern countries necessitates global initiatives and research to better understand the real biological risks associated with pesticide exposure, particularly concerning reproductive health, endocrine disruption, and carcinogenesis-key targets of these chemicals. Since 2001, the Brazilian Health Regulatory Agency (ANVISA) has operated the "Reports on Pesticide Residue Analysis in Food (RPRAF)" program to evaluate pesticide residues in food samples collected across Brazil. Despite its limitations, the program has been crucial in identifying the chemical exposome related to Brazilian agro-foods, facilitating studies on relevant pesticides, their doses, routes, and exposure schedules, and enabling the development of pre-clinical studies based on real-life exposure scenarios. A thorough understanding of the main mechanism of toxicity is crucial for raising awareness about the health risks associated with pesticide exposure, fostering tailored health strategies and guiding informed regulatory policies.

PMID:40151620 | PMC:PMC11947944 | DOI:10.3389/ftox.2025.1442801

Acta Med Philipp. 2025 Feb 28;59(3):70-79. doi: 10.47895/amp.vi0.9007. eCollection 2025.

ABSTRACT

BACKGROUND AND OBJECTIVE: Endocrine Disrupting Chemicals (EDCs) are ubiquitously found as low-level contaminants and pose serious threat to women's health. EDCs may result in various reproductive disorders, fetal birth and developmental abnormalities, and endocrine and metabolic disorders. EDCs can be detected in body fluids of exposed individuals including blood and urine. This study aimed to detect four EDCs - Methyl Paraben (MP), 2,4-Dichlorophenoxyacetic acid (2,4-D), Monobutyl Phthalate (MBP), and Bisphenol A (BPA) in urine samples of women using Ultra-Performance Liquid Chromatography - Quadrupole Time-of-Flight (UPLC-QTOF) mass spectrometry.

METHODS: Sequential steps of enzymatic deconjugation, liquid-liquid extraction, solid phase extraction, and liquid chromatography separation and mass spectrometry detection were optimized in urine samples. The method was used to analyze 70 urine samples from women of reproductive age.

RESULTS: The sample preparation method showed a recovery ranging from 86.6% (MBP) to 100 % (2,4-D). The method demonstrated limits of quantitation ranging from 1.52 ng/m(MP) to 6.46 ng/mL(2,4D). Intra-day precisions expressed as relative standard deviation were all below 15% while accuracy was shown to range from 67.10% (2,4-D) to 102.39% (MBP). MP was detected in nine samples (12.86%) with a geometric mean value of 10.15 ng/ml (range: 3.62-52.39 ng/ml). MBP was detected in 68 samples (97.14%) with a geometric mean value of 97.62 ng/ml (range: 15.32-698.18 ng/ml). BPA was detected only once (9.58 ng/ml) while 2, 4-D was not detected in all samples.

CONCLUSION: A UPLC-QTOF mass spectrometry method to detect four EDCs at parts per billion level (ng/ml) was adapted and applied for analysis of urine samples. This method can find applicability in routine testing of clinical specimens as well as surveillance and other epidemiological studies.

PMID:40151222 | PMC:PMC11936769 | DOI:10.47895/amp.vi0.9007

Int J Hyg Environ Health. 2025 Mar 27;266:114568. doi: 10.1016/j.ijheh.2025.114568. Online ahead of print.

ABSTRACT

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are emerging environmental contaminants with potential metabolic and endocrine-disrupting properties that may affect women's reproductive health. However, their specific role in pregnancy loss remains relatively understudied.

OBJECTIVES: This study aimed to assess the association between exposure to multiple PFAS and the association with pregnancy loss (PL) in a population from Northwest China using an environment-wide association study (EWAS) approach.

METHODS: A case-control study was conducted at a university-affiliated reproductive center, enrolling 348 women with a history of PL and 320 controls with at least one live birth and no history of pregnancy loss. Serum concentrations of ten PFAS were quantified using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) following a standardized extraction and purification protocol. Demographic and clinical data were collected via a structured questionnaire. An elastic net regression model (ENRM) was employed for variable selection, identifying PFASs to be included in the subsequent EWAS analysis. Associations between individual PFAS and PL were then evaluated using logistic regression, and EWAS was utilized to explore the overall associations between PFAS mixture exposure and PL, accounting for potential interactions and multicollinearity.

RESULTS: The EWAS identified five PFASs-PFPeS, PFHxS, PFOA, PFOS, and PFNA-with significantly higher exposure odds in pregnancy loss cases versus live birth controls (adjusted ORs: 1.82 [1.31-2.62], 1.34 [1.19-1.51], 1.73 [1.46-2.07], 1.33 [1.14-1.56], and 1.73 [1.40-2.15], respectively). Subgroup analyses confirmed robust associations, with PFOA consistently linked to elevated exposure odds across demographic and clinical strata.

CONCLUSION: This study demonstrates a significant association between exposure to multiple PFAS, notably PFPeS, PFHxS, PFOA, PFOS, and PFNA, and an increased risk of pregnancy loss in a Northwest Chinese population. The particularly robust association observed with PFOA across diverse subgroups underscores its potential as a significant environmental risk factor for PL. These findings highlight the need for further research to elucidate the underlying mechanisms and to develop strategies for reducing PFAS exposure among women of reproductive age.

PMID:40154148 | DOI:10.1016/j.ijheh.2025.114568

Biomedicines. 2025 Mar 19;13(3):748. doi: 10.3390/biomedicines13030748.

ABSTRACT

Background/Objectives: Flavonoids are common ubiquitous components of plants and are consumed by humans and livestock in their diets. Many different activities have been proposed for a variety of flavonoids that play a role in the benefits of a plant-rich diet. On the downside, excessive exposure to some flavonoids comes with a risk of endocrine disruption. Our objective was to define the structural elements of flavones and selected other flavonoids required for endocrine-disrupting activities on each of four steroid receptors, estrogen, androgen, progesterone, and glucocorticoid receptors. Methods: This work presents a systematic screen for the hormone agonist or antagonist activity of a selected panel of flavonoids on estrogen, androgen, progesterone, and glucocorticoid receptors. The screen is focused on the positional requirements of hydroxyl substituents on the flavone backbone. Results: Each receptor exhibited a distinct pattern for structural requirements of the flavones to impact receptor signaling. The most active flavones exhibited antagonist activity on androgen and progesterone receptors with an IC₅₀ of 0.5 and 2 µM, respectively. Flavones only exhibited weak antagonism on glucocorticoid receptors. When active, flavones acted as estrogen receptor agonists. The findings were utilized to design and synthesize a novel flavone, 3-fluoro, 6,4'-dihydroxyflavone 14, that displays increased potency as an estrogen agonist (EC₅₀~30 nM). Modeling of the binding of this novel flavone predicts increased preference for ERα versus ERβ relative to the estrogenic phytoestrogen, genistein. Conclusions: The structural requirements for flavones to act as estrogen agonists and antagonists of other steroid receptors are defined. The synthesis of a novel flavone offers potential for topical applications where systemic estrogen activity is undesired. However, the results highlight the potential for endocrine disruption when certain flavones are consumed in quantity as supplements.

PMID:40149724 | PMC:PMC11940309 | DOI:10.3390/biomedicines13030748

Sci Total Environ. 2025 Mar 27;974:179253. doi: 10.1016/j.scitotenv.2025.179253. Online ahead of print.

ABSTRACT

Parabens are widely used preservatives with endocrine-disrupting properties, but their role in glucose metabolism during pregnancy is unclear. This study examines prospective associations between urinary concentrations of four parabens in early and mid-pregnancy and gestational diabetes (GDM). A matched case-control study nested within a diverse longitudinal pregnancy cohort (PETALS) with universal GDM screening matched GDM cases to two controls (111 cases; 222 controls). Urine samples collected 2015-2017 in early (14 ± 2.3 weeks) and mid-pregnancy (20 ± 2.4 weeks) were analyzed for paraben concentrations with mass spectrometry. Area-under-the-time-concentration-curve (AUC) assessed cumulative exposure. Conditional logistic regression models evaluated associations between paraben concentrations and GDM, adjusting for covariates. We a priori examined effect modification by Asian/Pacific Islander (A/PI) race/ethnicity due to the case-control matching and GDM prevalence highest among A/PI. Participants were 31 ± 5 years old and 40 % A/PI, 33 % Hispanic, 14 % White and 9 % Black. Methylparaben and propylparaben had >94 % detection, while ethylparaben and butylparaben ranged from 22 %-51 %. Paraben exposure was not associated with GDM overall. Among A/PI, higher methylparaben concentrations exhibited higher odds of GDM: early-pregnancy OR 1.14 per IQR (95 % CI: 0.89,1.45) and AUC 1.07 (0.89,1.30) compared to non-A/PI (early-pregnancy 0.81 [0.62,1.06] and AUC 0.70 [0.44,1.12]; P_interaction = 0.01 and 0.03, respectively). A/PI mid-pregnancy ethylparaben exposure (detectable vs non-detectable) was linked to higher GDM odds (2.00 [0.84,4.76] vs. non-A/PI 0.47 [0.17,1.27]; P_interaction = 0.04) as was mid-pregnancy propylparaben exposure (Tertile 2 vs. 1: 3.67 [1.21,11.1] vs. non-A/PI 0.70 [0.22, 2.25]; P_interaction = 0.04). Although overall paraben exposure was not associated with GDM, interactions by A/PI race/ethnicity suggested potential increased odds of GDM related to propylparaben, methylparaben, and ethylparaben exposure. Future studies should explore paraben exposure in diverse populations.

PMID:40154079 | DOI:10.1016/j.scitotenv.2025.179253

Int J Hyg Environ Health. 2025 Mar 27;266:114568. doi: 10.1016/j.ijheh.2025.114568. Online ahead of print.

ABSTRACT

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are emerging environmental contaminants with potential metabolic and endocrine-disrupting properties that may affect women's reproductive health. However, their specific role in pregnancy loss remains relatively understudied.

OBJECTIVES: This study aimed to assess the association between exposure to multiple PFAS and the association with pregnancy loss (PL) in a population from Northwest China using an environment-wide association study (EWAS) approach.

METHODS: A case-control study was conducted at a university-affiliated reproductive center, enrolling 348 women with a history of PL and 320 controls with at least one live birth and no history of pregnancy loss. Serum concentrations of ten PFAS were quantified using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) following a standardized extraction and purification protocol. Demographic and clinical data were collected via a structured questionnaire. An elastic net regression model (ENRM) was employed for variable selection, identifying PFASs to be included in the subsequent EWAS analysis. Associations between individual PFAS and PL were then evaluated using logistic regression, and EWAS was utilized to explore the overall associations between PFAS mixture exposure and PL, accounting for potential interactions and multicollinearity.

RESULTS: The EWAS identified five PFASs-PFPeS, PFHxS, PFOA, PFOS, and PFNA-with significantly higher exposure odds in pregnancy loss cases versus live birth controls (adjusted ORs: 1.82 [1.31-2.62], 1.34 [1.19-1.51], 1.73 [1.46-2.07], 1.33 [1.14-1.56], and 1.73 [1.40-2.15], respectively). Subgroup analyses confirmed robust associations, with PFOA consistently linked to elevated exposure odds across demographic and clinical strata.

CONCLUSION: This study demonstrates a significant association between exposure to multiple PFAS, notably PFPeS, PFHxS, PFOA, PFOS, and PFNA, and an increased risk of pregnancy loss in a Northwest Chinese population. The particularly robust association observed with PFOA across diverse subgroups underscores its potential as a significant environmental risk factor for PL. These findings highlight the need for further research to elucidate the underlying mechanisms and to develop strategies for reducing PFAS exposure among women of reproductive age.

PMID:40154148 | DOI:10.1016/j.ijheh.2025.114568

Mar Pollut Bull. 2025 Mar 26;215:117870. doi: 10.1016/j.marpolbul.2025.117870. Online ahead of print.

ABSTRACT

Contaminants of emerging concern (CECs) in estuaries have received increasing attention due to their potential environmental impacts. However, detailed analyses of the sources, transport mechanisms, and environmental consequences of these contaminants remain limited. This study applied non-target screening technology to comprehensively assess CECs in the Nandu River estuary. A total of 18,000 characteristic features were screened, revealing a greater number of hydrophobic features in seawater than in the estuary. Systematic classification identified 74, 195, and 48 compounds at Levels 1, 2, and 4 respectively, with primary classifications comprising pharmaceuticals (34 %), industrial materials (23 %), pesticides (18 %), and natural products (17 %). Semi-quantitative analysis employing external standards revealed elevated concentrations of 61 monitored contaminants in estuarine zones compared to offshore waters, with Climbazole exhibiting peak concentration levels. Ecological risk assessment identified 12 contaminants of emerging concern (CECs) requiring prioritized monitoring (with RQ > 1). A priority list was established based on the frequency of detection, bioaccumulation potential, persistence, toxicity and endocrine disruption potential of the compounds. 64 CECs were identified as high priority, consisting mainly of pesticides and pharmaceutical compounds. Pesticides originate primarily from upstream agricultural activities, decreasing in concentration downstream, whereas pharmaceuticals, industrial materials, and natural products are linked to domestic sewage. Tidal cycles play a crucial role in modulating the distribution and concentration of CECs within estuarine waters. This modulation is attributed to the dynamic interaction between terrestrial inputs and coastal influences, where high tides contribute significantly to the dilution of land-derived pollutants.

PMID:40147050 | DOI:10.1016/j.marpolbul.2025.117870

Environ Int. 2025 Mar 20;198:109400. doi: 10.1016/j.envint.2025.109400. Online ahead of print.

ABSTRACT

Despite growing awareness of endocrine disrupting chemicals (EDCs), knowledge gaps remain regarding their effects on human brain development. EDC risk assessment focuses primarily on EATS modalities (estrogens, androgens, thyroid hormones, and steroidogenesis), overlooking the broader range of hormone receptors expressed in the developing brain. This limits the evaluation of chemicals for their potential to cause endocrine disruption-mediated developmental neurotoxicity (ED-DNT). The Neurosphere Assay, an in vitro test method for developmental neurotoxicity (DNT) evaluation, is an integral component of the DNT in vitro testing battery, which has been used to screen a broad domain of environmental chemicals. Here, we define the endocrine-related applicability domain of the Neurosphere Assay by assessing the impact and specificity of 14 hormone receptors on seven key neurodevelopmental processes (KNDPs), neural progenitor cell (NPC) proliferation, migration of radial glia, neurons, and oligodendrocytes, neurite outgrowth, and differentiation of neurons and oligodendrocytes. Comparative analyses in human and rat NPCs of both sexes revealed species- and sex-specific responses. Mechanistic insights were obtained through RNA sequencing and agonist/antagonist co-exposures. Most receptor agonists modulated KNDPs at concentrations in the range of physiologically relevant hormone concentrations. Phenotypic effects induced by glucocorticoid receptor (GR), liver X receptor (LXR), peroxisome proliferator-activated receptor beta/delta (PPARβδ), retinoic acid receptor (RAR) and retinoid X receptor (RXR) activation were counteracted by receptor antagonists, confirming specificity. Transcriptomics highlighted receptor crosstalk and the involvement of conserved developmental pathways (e.g. Notch and Wnt). Species comparisons identified limited concordance in hormone receptor-regulated KNDPs between human and rat NPCs. This study presents novel findings on cellular and molecular hormone actions in human fetal NPCs, highlights major species differences, and illustrates the Neurosphere Assay's relevance for detecting endocrine MoAs, supporting its application in human-based ED-DNT risk assessment.

PMID:40147140 | DOI:10.1016/j.envint.2025.109400

Food Chem Toxicol. 2025 Mar 25:115410. doi: 10.1016/j.fct.2025.115410. Online ahead of print.

ABSTRACT

Current research on endocrine-disrupting effects of colorants utilized in food contact materials (FCMs) ramains limited. This study investigated these effects through in vitro cell models and in silico toxicological models. A total of 24 synthetic colorants were collected from the Chinese market, including azo, anthraquinone, heterocyclic and fused-ring ketones, and phthalocyanines. Their endocrine-disrupting effects mediated by estrogen and androgen receptors were evaluated using an in vitro dual-luciferase reporter gene assay. Results showed no estrogenic or anti-estrogenic effects or androgenic activity in the colorants. However, three colorants, C.I. Pigment Red 177, C.I. Pigment Orange 71, and C.I. Pigment Blue 15, elicited anti-androgenic effects with 20% relative inhibitory concentrations (RIC₂₀) of 13.08, 40.52, and 33.27 μg/mL, respectively. In addition, in silico toxicological models predicted the endocrine-disrupting activity of the 24 colorants, showing predictive accuracy ranging from 35% to 100% consistency with in vitro experimental outcomes. Molecular docking revealed strong binding affinity and mechanisms of interaction between three colorants and the human androgen receptor. In summary, this study combined in vitro experiments and in silico toxicological models to investigate the endocrine-disrupting effects of organic colorants with different structural types, providing new insights perspective on health risks associated with their use in FCMs.

PMID:40147811 | DOI:10.1016/j.fct.2025.115410

Chemosphere. 2025 Mar 26;377:144315. doi: 10.1016/j.chemosphere.2025.144315. Online ahead of print.

ABSTRACT

Understanding the impact of endocrine disruptor compounds (EDCs) across a wide range of species is crucial, given their ubiquitous presence. Although invertebrate species lack sex steroid hormone pathways, they exhibit sensitivity to EDCs, which could affect population dynamics. This study assessed reproductive endpoints and oxidative stress parameters in Eisenia fetida following exposure to estradiol and soy isoflavones, resembling the concentrations found in livestock manure. The experiment used artificial soil, as recommended by OECD guidelines (7:2:1 sand, kaolin and peat). Adult specimens were randomly divided into seven groups (n = 11/replicate): one control, three estradiol (156.1, 283.4 and 633.8 μg/kg of dry soil) and three soy isoflavones (113.0, 215.3 and 405.0 mg/kg of dry soil) concentrations. After eight weeks, samples were collected for cytological, histological and biochemical analysis. Offspring development was assessed after 12 additional weeks. Higher estradiol and isoflavone concentrations led to lower germ cell number and increased abnormalities, especially in the seminal vesicles and ovaries. Catalase and peroxidase activities were significantly increased in all treated groups. The exposure did not significantly affect the number of E. fetida offspring. These findings highlight E. fetida's sensitivity to EDCs at a biochemical and tissue level, suggesting its use as a bioindicator for assessing EDC contamination in soils.

PMID:40147346 | DOI:10.1016/j.chemosphere.2025.144315

Environ Health (Wash). 2025 Jan 27;3(3):321-333. doi: 10.1021/envhealth.4c00218. eCollection 2025 Mar 21.

ABSTRACT

The local interpretable model-agnostic explanation method was used to unveil substructures (toxic alerts) that cause endocrine disruption in chemical compounds using machine learning models. The random forest classifier was applied to build explainable models with the TOX21 data sets after data curation. Using these models applied to the EDC and EDKB-FDA data sets, the substructures that cause endocrine disruption in chemical compounds were unveiled, providing stable, more specific, and consistent explanations, which are essential for trust and acceptance of the findings, mainly due to the difficulty of finding relevant experimental evidence for different receptors (androgen, estrogen, aryl hydrocarbon, aromatase, and peroxisome proliferator-activated receptors). This approach is significant because of its contribution to the interpretability of explainable machine learning algorithms, particularly in the context of unveiling substructures associated with endocrine disruption in five targets (androgen receptor, estrogen receptor, aryl hydrocarbon receptors, aromatase receptors, and peroxisome proliferator-activated receptors), thereby advancing the relevant field of environmental toxicology, where a careful evaluation of the potential risks of exposure to new compounds is needed. The specific substructures thiophosphate, sulfamate, anilide, carbamate, sulfamide, and thiocyanate are presented as toxic alerts that cause endocrine disruption to better understand their potential risks and adverse effects on human health and the environment.

PMID:40144324 | PMC:PMC11934200 | DOI:10.1021/envhealth.4c00218

Environ Health (Wash). 2024 Nov 22;3(3):271-281. doi: 10.1021/envhealth.4c00202. eCollection 2025 Mar 21.

ABSTRACT

Gestational diabetes mellitus (GDM) is a type of diabetes that arises during pregnancy, leading to long-term adverse consequences for maternal health and fetal development. However, the specific role of endocrine-disrupting chemicals (EDCs) in the pathogenesis of GDM remains controversial. This prospective cohort study sought to investigate how coexposure to bisphenols, parabens, triclosan (TCS), benzophenone-type UV filters, and neonicotinoids (NEOs) affects the odds of GDM. Quantile-based g-computation and Bayesian kernel machine regression showed a significant inverse relationship between EDC mixtures and the reduced risk of GDM (OR = 0.34, 95% CI: 0.13-0.87), which was mainly explained by bisphenol (OR = 0.49, 95% CI: 0.29-0.80) and paraben (OR = 0.60, 95% CI: 0.40-0.91) exposure. Bisphenol S (BPS), bisphenol Z (BPZ), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP) were identified as key contributors to the joint effect. In addition, subgroup analyses suggested that the bisphenols-GDM association was more pronounced in younger/normal-weight participants. The sex-specific impact of exposure to bisphenols on the development of GDM was observed, whereas the second trimester represented a critical window for EDC exposure. Continued research efforts, focusing on causal pathways and nonmonotonic relationships, will be crucial to elucidate the complex influence of EDC exposure on the development of GDM.

PMID:40144318 | PMC:PMC11934205 | DOI:10.1021/envhealth.4c00202

Int J Mol Sci. 2025 Mar 17;26(6):2709. doi: 10.3390/ijms26062709.

ABSTRACT

Flutamide (FL), a non-steroidal drug used for its antiandrogenic, anticancer, and disrupting endocrine properties, induces mitochondrial toxicity and drug metabolism enzymes and promotes hepatocarcinogenesis. The inhibition of mitophagy, leading to the accumulation of damaged mitochondria, is implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the effects of FL in high-fat diet (HFD)-induced non-obese steatosis rats, categorized into four groups: basal diet (BD), BD + FL, HFD, and HFD + FL. The FL exacerbated HFD-induced steatosis and marginally increased preneoplastic lesions. To analyze hepatic preneoplastic lesions, we divided them into clusters based on the expression ratios of the mitophagy regulators LC3 and AMBRA1. The expression rates of LC3 and AMBRA1 in these precancerous lesions were classified into three clusters using k-means clustering. The HFD group exhibited an increased ratio of mitophagy inhibition clusters, as indicated by decreased LC3 and increased AMBRA1 levels in background hepatocytes and preneoplastic lesions. FL counteracted HFD-mediated mitophagy inhibition, as indicated by increased LC3 and decreased AMBRA1 levels in background hepatocytes. Our clustering analysis revealed that FL-induced mitophagy induction relied on Parkin expression. The present study underscores the significance of cluster analysis in understanding the role of mitophagy within small preneoplastic lesions and suggests that FL may potentially exacerbate NAFLD-associated hepatocarcinogenesis by affecting mitophagy.

PMID:40141351 | PMC:PMC11943065 | DOI:10.3390/ijms26062709

Life (Basel). 2025 Mar 3;15(3):392. doi: 10.3390/life15030392.

ABSTRACT

Micro- and nano-plastics (MNPs) are small plastic particles that result from the breakdown of larger plastics. They are widely dispersed in the environment and pose a threat to wildlife and humans. MNPs are present in almost all everyday items, including food, drinks, and household products. Air inhalation can also lead to exposure to MNPs. Research in animals indicates that once MNPs are absorbed, they can spread to various organs, including the liver, spleen, heart, lungs, thymus, reproductive organs, kidneys, and even the brain by crossing the blood-brain barrier. Furthermore, MPs can transport persistent organic pollutants or heavy metals from invertebrates to higher levels in the food chain. When ingested, the additives and monomers that comprise MNPs can disrupt essential biological processes in the human body, thereby leading to disturbances in the endocrine and immune systems. During the 2019 coronavirus (COVID-19) pandemic, there was a significant increase in the global use of polypropylene-based face masks, leading to insufficient waste management and exacerbating plastic pollution. This review examines the existing research on the impact of MNP inhalation on human lung and kidney health based on in vitro and in vivo studies. Over the past decades, a wide range of studies suggest that MNPs can impact both lung and kidney tissues under both healthy and diseased conditions. Therefore, this review emphasizes the need for additional studies employing multi-approach analyses of various associated biomarkers and mechanisms to gain a comprehensive and precise understanding of the impact of MNPs on human health.

PMID:40141737 | PMC:PMC11944196 | DOI:10.3390/life15030392

Toxics. 2025 Feb 23;13(3):151. doi: 10.3390/toxics13030151.

ABSTRACT

Polycyclic aromatic hydrocarbons (PAHs) are a group of organic compounds with fused aromatic rings, primarily derived from combustion processes and environmental pollutants. This narrative review discusses the most relevant studies on PAHs, focusing on their sources, environmental and occupational exposure, and effects on human health, emphasizing their roles as carcinogenic, mutagenic, and teratogenic agents. The primary pathways for human exposure to PAHs are through the ingestion of contaminated food (mainly due to some food processing methods, such as smoking and high-temperature cooking techniques), the inhalation of ambient air, and the smoking of cigarettes. Coke oven workers are recognized as a high-risk occupational group for PAH exposure, highlighting the need for appropriate strategies to mitigate these risks and safeguard worker health. PAHs are metabolized into reactive intermediates in the body, which can lead to DNA damage and promote the development of various health conditions, particularly in environments with high exposure levels. Chronic PAH exposure has been linked to respiratory diseases, as well as cardiovascular problems and immune system suppression. Furthermore, this review underscores the significant impact of PAHs on reproductive health. The results of the reported studies suggest that both male and female fertility can be compromised due to oxidative stress, DNA damage, and endocrine disruption caused by PAH exposure. In males, PAHs impair sperm quality, while, in females, they disrupt ovarian function, potentially leading to infertility, miscarriage, and birth defects. Fetal exposure to PAHs is also associated with neurodevelopmental disorders. Given the extensive and detrimental health risks posed by PAHs, this review stresses the importance of stringent environmental regulations, occupational safety measures, and public health initiatives to mitigate exposure and safeguard reproductive and overall health.

PMID:40137477 | PMC:PMC11946043 | DOI:10.3390/toxics13030151

Toxics. 2025 Feb 25;13(3):162. doi: 10.3390/toxics13030162.

ABSTRACT

Bisphenol S (BPS) is a widespread environmental endocrine disrupter that can cause hepatotoxicity, neurotoxicity and negative effects on reproduction. Puerarin (PUE) has been found to have anti-inflammatory, antioxidant, and neuroprotective properties, however, its potential protective effects against BPS-induced neurotoxicity and the underlying mechanisms are still not fully understood. In this study, HT22 cells were exposed to different concentrations of BPS with or without PUE. Cell viability, apoptosis, oxidative damage, and the expression level of axon-injury-related genes and the BDNF/TrkB/CREB pathway were analyzed. The results showed that 40 μM to 180 μM BPS and 100 μM to 180 μM PUE significantly decreased the cell viability of HT22 cells, but in the 80 μM PUE group, the cell viability was higher than control group, and the ratio of 1.1. Meanwhile, BPS increased the production of ROS and MDA but decreased the GSH and SOD. However, supplementation with PUE was alleviated the oxidative damage. PUE also alleviated the apoptosis rate that induced by BPS. Additionally, BPS decreased the expression levels of mRNA and proteins of synaptic-related genes, but inhibited the expression levels of mRNA and proteins of the BDNF/TrkB/CREB signaling pathway. Interestingly, PUE was found to significantly recover the expression of synaptic related genes, but also upregulated the expression of the BDNF/TrkB/CREB pathway. In conclusion, our study proved that PUE can attenuate the neurotoxicity effect of bisphenol S, which related to oxidative damage in HT22 cells by regulating the BDNF/TrkB/CREB signaling pathway. This study is not only the first to demonstrate that PUE can mitigate BPS-induced neurotoxicity through oxidative stress modulation, but also provides a novel therapeutic approach involving the BDNF/TrkB/CREB pathway. These findings offer promising insights into natural-based strategies for protecting against environmental neurotoxins and provide a foundation for future therapeutic developments targeting BPS-induced neurotoxicity.

PMID:40137489 | PMC:PMC11945520 | DOI:10.3390/toxics13030162

Toxics. 2025 Feb 26;13(3):164. doi: 10.3390/toxics13030164.

ABSTRACT

Bisphenols (BPs) are a group of organic compounds used extensively in plastics, coatings, and epoxy resins; they have been of concern recently due to their endocrine-disrupting effects. Among these, bisphenol A (BPA) is the most studied. Regulatory measures, such as the ban on BPA use in baby bottles by the European Union and its restricted use in thermal paper, reflect the growing awareness of the health risks of BPA. To mitigate these risks, analogs such as bisphenol S (BPS), bisphenol F (BPF), and others (BPAF, BPAP, BPB, BPP, BPZ) have been developed as alternatives. Despite their intended safety, these analogs have been detected in environmental media, including indoor dust and thermal receipt paper, as well as in human biological samples. Studies report their presence in urine at levels comparable to BPA, with BPS and BPF found in 78% and 55% of samples, respectively. In addition, BPs have been found in human follicular fluid (FF) at concentrations that could exert some paracrine effects on ovarian function and reproductive health. With the increased global production of BPs, occupational exposure and environmental contamination also increase. This review summarizes what is currently known about the effects of BPs on the ovary and the mechanisms by which PBs exert ovarian toxicity, with a particular focus on oogenesis, folliculogenesis, and steroidogenesis. Further, this review emphasizes their influence on reproductive functions and the need for further biosafety evaluations.

PMID:40137491 | PMC:PMC11946734 | DOI:10.3390/toxics13030164

Toxics. 2025 Feb 27;13(3):172. doi: 10.3390/toxics13030172.

ABSTRACT

Di (2-ethylhexyl) phthalate (DEHP) is an acknowledged endocrine disruptor with male reproductive toxicity; nevertheless, the transgenerational impacts on male offspring resulting from paternal exposure, along with the mechanisms involved, are not well understood. To develop a transgenerational model of DEHP paternal exposure, male C57BL/6J mice (4-week) exposed to DEHP (5, 250, and 500 mg/kg/d) for 35 days were then bred with unexposed female mice at a ratio of 1:2 to produce offspring. Findings indicate that the sperm quality and relative sex hormones were adversely affected in males of F1 and F2 generations, and pathological damage in the testes and the apoptosis of testicular cells were also observed. Interestingly, an increase in the expression levels of H3K27me3 was observed in the testicular tissues of male descendants. It was further confirmed by in vitro approach that H3K27me3 may down-regulate the expression of Bcl-2 and plays a role in regulating the initiation of apoptosis in Leydig cells triggered by MEHP (the primary metabolite of DEHP). Additionally, the down-regulation of Bcl-2 can be reversed by treatment with the H3K27me3 inhibitor GSK126. To conclude, DEHP leads to transgenerational harm to male offspring reproductive systems, with the epigenetic mechanism of H3K27me3 playing a key role in mediating these effects.

PMID:40137499 | PMC:PMC11945355 | DOI:10.3390/toxics13030172

Toxics. 2025 Mar 5;13(3):187. doi: 10.3390/toxics13030187.

ABSTRACT

Chemicals in personal care and consumer products are suspected to disrupt endocrine function and affect reproductive health. However, the link between mixed exposure and long-term amenorrhea is not well understood. This study analyzed data from 684 women (2013-2018 National Health and Nutrition Examination Survey) to assess exposure to eight polyfluorinated alkyl substances (PFASs), 15 phthalates (PAEs), six phenols, and four parabens. Various statistical models for robustness tests and mediation analysis were used to explore associations with long-term amenorrhea and the role of serum globulin. Biological mechanisms were identified through an integrated strategy involving target analysis of key chemicals and long-term amenorrhea intersections, pathway analysis, and target validation. Results showed that women with long-term amenorrhea had higher exposure levels of Perfluorodecanoic acid, Perfluorohexane sulfonic acid (PFHxS), Perfluorononanoic acid, n-perfluorooctanoic acid (n_PFOA), n-perfluorooctane sulfonic acid, and Perfluoromethylheptane sulfonic acid isomers. Logistic regression with different adjustments consistently found significant associations between elevated PFAS concentrations and increased long-term amenorrhea risk, confirmed by Partial Least Squares Discriminant Analysis. Mediation analysis revealed that serum globulin partially mediated the relationship between PFAS exposure and long-term amenorrhea. Network and target analysis suggested that PFHxS and n_PFOA may interact with Signal Transducer and Activator of Transcription 3 (STAT3). This study highlights significant associations between PFAS exposure, particularly PFHxS and n_PFOA, and long-term amenorrhea, with serum globulin and STAT3 serving as mediators in the underlying mechanisms.

PMID:40137514 | PMC:PMC11945380 | DOI:10.3390/toxics13030187

Toxics. 2025 Mar 19;13(3):225. doi: 10.3390/toxics13030225.

ABSTRACT

The concentrations and spreading of eight synthetic and two natural progestins (PGs) were investigated in surface waters from ten sites at the Douro River Estuary. Samples were filtrated and subjected to solid-phase extraction (SPE) to isolate and concentrate the target PGs. The extracts were cleaned by silica cartridges and analyzed by LC-MS/MS. The finding of biologically relevant amounts of gonanes (22.3 ± 2.7 ng/L), progesterone derivatives (12.2 ± 0.5 ng/L), drospirenone (4.1 ± 0.8 ng/L), and natural PGs (9.4 ± 0.9 ng/L) support the possibility of these compounds acting as endocrine disruptors. Despite the absence of significant differences amongst sampling sites and seasons, the principal component analysis (PCA) and the linear discriminant analysis (LDA) approaches reveal that spring and summer have different patterns of PG distribution compared to autumn and winter. The assessment of risk coefficients (RQs) and the potential concentrations of synthetic progestins in fish blood sustains that all tested compounds pose a significant risk to local biota (RQs > 1). Additionally, three progestins-norethindrone, norethindrone acetate, and medroxyprogesterone acetate-should reach human-equivalent therapeutic levels in fish plasma. Overall, the current data show PGs' presence and potential impacts in one of the most important estuaries of the Iberian Peninsula.

PMID:40137552 | PMC:PMC11946473 | DOI:10.3390/toxics13030225

Toxics. 2025 Mar 20;13(3):228. doi: 10.3390/toxics13030228.

ABSTRACT

As novel pollutants, flame retardants (FRs) are prone to accumulating in soil and might increase human health risks. It is advisable to emphasize the biomagnification of FRs within the terrestrial food chain, particularly concerning mammals occupying higher trophic levels. Exposure to soil particles laden with FRs may result in numerous health complications. These findings offer significant insights into FR pollutant profiles, tracing origins and recognizing health risks associated with soil samples. Reports have revealed that exposure to FRs can pose serious health risks, including neurodevelopmental impairments, endocrine system disruption, and an increased likelihood of cancer. Nanomaterials, with their high surface area and flexible properties, possess the ability to utilize light for catalytic reactions. This unique capability allows them to effectively degrade harmful contaminants, such as FRs, in soil. Additionally, biological degradation, driven by microorganisms, offers a sustainable method for breaking down these pollutants, providing an eco-friendly approach to soil remediation. These approaches, combined with optimum remediation strategies, hold great potential for effectively addressing soil contamination in the future. Further research should prioritize several key areas, including ecological behavior, contaminant monitoring, biological metabolomics, toxicity evaluation, and ecological impact assessment.

PMID:40137555 | PMC:PMC11946183 | DOI:10.3390/toxics13030228

Horm Res Paediatr. 2025 Mar 26:1-20. doi: 10.1159/000545043. Online ahead of print.

ABSTRACT

BACKGROUND: Obesity is a disease, acknowledged by WHO, characterized as an epidemic in a worldwide range, particularly in Western countries. Childhood obesity, lately, has raised major concerns. Among the complex factors contributing to obesity, environmental factors, such as endocrine disruptors (EDs) are gaining attention as emerging contributors to obesity.

SUMMARY: Toxicants, such as bisphenol A, phthalates, perfluoroalkyl and polyfluoroalkyl substances, heavy metals, and pesticides have been associated with increases in the incidence of obesity in human populations, animals, and cellular models. These EDCs, called obesogens, disrupt the endocrine system across multiple pathways. They influence appetite, promote inflammation, disrupt the ecology and function of the gut microbiome, and induce transgenerational epigenetic changes. At the cellular level, they act as agonists of peroxisome proliferator-activated receptor γ, steroid, and aryl hydrocarbon receptors.

KEY MESSAGES: Children are exposed to obesogens through multiple metabolic pathways, which contribute directly and indirectly to the development of obesity. Despite the increasing evidence, more studies are needed to identify additional obesogens and elucidate their mechanisms of action to minimize exposure to pediatric and adolescent populations.

PMID:40139165 | DOI:10.1159/000545043

Brain Res Bull. 2025 Mar 24;224:111317. doi: 10.1016/j.brainresbull.2025.111317. Online ahead of print.

ABSTRACT

Down syndrome (DS), caused by an extra copy of chromosome 21, is the most prevalent chromosomal disorder. It leads to various complications including, cardiac and endocrine dysfunctions, impairment of the immune system, growth retardation, and certain neurological conditions. Stunted growth in this population might be linked to an increased risk of a variety of co-occurring conditions, particularly neurological disorders. Studies indicate that the levels of neurodegeneration and neuroinflammation markers are higher in shorter children with DS. The disruption of insulin-like growth factor 1 (IGF1) signalling pathway due to the overexpression of proinflammatory cytokine genes could help establish a connection between short stature and neurodegeneration in DS. These cytokines disrupt the production of IGF1 in the liver, thereby inhibiting IGF1 from promoting bone and brain growth. Additionally, elevated cytokines levels impair the production of sex hormones by affecting the gonadal axis, further exacerbating the aforementioned conditions. The group of GnRH neurons responsible for cognitive functions is also impaired in DS, and treatment with GnRH agonists has demonstrated improvements in cognition. Although GnRH agonists can delay the fusion of growth plates by inhibiting pulsatile GnRH secretion, they may also lead to cognitive impairments. Hypothyroidism, the most prevalent endocrine complication of DS, can also contribute to both cognitive impairment and short stature. In conclusion, the increase of proinflammatory cytokines, through various mechanisms, can play a significant role in the development of both cognitive impairments and short stature in DS.

PMID:40139281 | DOI:10.1016/j.brainresbull.2025.111317

Toxics. 2025 Mar 5;13(3):187. doi: 10.3390/toxics13030187.

ABSTRACT

Chemicals in personal care and consumer products are suspected to disrupt endocrine function and affect reproductive health. However, the link between mixed exposure and long-term amenorrhea is not well understood. This study analyzed data from 684 women (2013-2018 National Health and Nutrition Examination Survey) to assess exposure to eight polyfluorinated alkyl substances (PFASs), 15 phthalates (PAEs), six phenols, and four parabens. Various statistical models for robustness tests and mediation analysis were used to explore associations with long-term amenorrhea and the role of serum globulin. Biological mechanisms were identified through an integrated strategy involving target analysis of key chemicals and long-term amenorrhea intersections, pathway analysis, and target validation. Results showed that women with long-term amenorrhea had higher exposure levels of Perfluorodecanoic acid, Perfluorohexane sulfonic acid (PFHxS), Perfluorononanoic acid, n-perfluorooctanoic acid (n_PFOA), n-perfluorooctane sulfonic acid, and Perfluoromethylheptane sulfonic acid isomers. Logistic regression with different adjustments consistently found significant associations between elevated PFAS concentrations and increased long-term amenorrhea risk, confirmed by Partial Least Squares Discriminant Analysis. Mediation analysis revealed that serum globulin partially mediated the relationship between PFAS exposure and long-term amenorrhea. Network and target analysis suggested that PFHxS and n_PFOA may interact with Signal Transducer and Activator of Transcription 3 (STAT3). This study highlights significant associations between PFAS exposure, particularly PFHxS and n_PFOA, and long-term amenorrhea, with serum globulin and STAT3 serving as mediators in the underlying mechanisms.

PMID:40137514 | PMC:PMC11945380 | DOI:10.3390/toxics13030187

Endocr J. 2025 Mar 27. doi: 10.1507/endocrj.EJ25-0035. Online ahead of print.

ABSTRACT

Hypopituitarism, characterized by reduced secretion of pituitary hormones, profoundly impacts systemic metabolic homeostasis and quality of life. Its etiology ranges from congenital anomalies in pituitary development to acquired conditions involving inflammation and autoimmune processes. Despite advances in understanding its pathogenesis, diagnostic challenges persist, particularly in cases with complex extra-pituitary manifestations or novel genetic variations. Congenital hypopituitarism often stems from disruptions in transcription factors and signaling pathways critical for pituitary organogenesis. Emerging studies employing next-generation sequencing and developmental biology techniques have revealed new genetic loci and mechanisms implicated in combined pituitary hormone deficiency. However, the pathogenesis of most congenital cases remains elusive, underscoring the need for functional and phenotypic analyses of novel variants. Acquired hypopituitarism, frequently associated with pituitary tumors or systemic diseases, has also been increasingly linked to autoimmune mechanisms. Notably, the concept of paraneoplastic autoimmune hypophysitis has emerged, highlighting malignancy-driven immune responses as a novel etiological framework. Investigations into immune checkpoint inhibitor-related hypophysitis and anti-PIT-1 hypophysitis exemplify the intricate interplay between tumor immunity and endocrine dysfunction, suggesting shared mechanisms involving ectopic antigen expression and autoimmunity. This review synthesizes recent insights into the genetic, developmental, and immunological underpinnings of hypopituitarism. By exploring both congenital and acquired etiologies, we aim to bridge gaps in the current understanding of this complex disorder and provide a foundation for improved diagnostic and therapeutic strategies. Future perspectives emphasize the integration of advanced genetic tools, deeper exploration of tumor-immunity interactions, and a heightened focus on extra-pituitary phenotypes to refine clinical practice and enhance patient outcomes.

PMID:40139845 | DOI:10.1507/endocrj.EJ25-0035

Diabetologia. 2025 Mar 25. doi: 10.1007/s00125-025-06409-3. Online ahead of print.

ABSTRACT

AIMS/HYPOTHESIS: Diabetes is a global health burden characterised by incremental beta cell loss. Islet transplantation is a recognised treatment for individuals with type 1 diabetes and hypoglycaemia unawareness but broader application is constrained by limited islet survival and function post-transplantation. The underlying molecular mechanisms that induce beta cell dysfunction and demise remain unclear, and therapeutic agents that protect against cellular loss and maintain insulin secretion are in demand as potential treatment options. CD47 is a cell surface protein implicated in cellular stress responses but its role in beta cell function remains relatively unexplored. We hypothesised that modulating CD47 expression would demonstrate a cytoprotective effect in beta cells.

METHODS: We used primary murine islets with/without genetic deletion of CD47, as well as human islets and MIN6 cells subjected to pharmacological disruption of CD47 signalling (siRNA or blocking antibody). Metabolic stress was induced in cells by exposure to hypoxia, hyperglycaemia or thapsigargin, and markers of the unfolded protein response, cell survival and insulin secretory function were assessed. Human pancreases from individuals with and without diabetes were examined for evidence of CD47 signalling.

RESULTS: Expression of CD47 and its high affinity ligand thrombospondin-1 (TSP1) was robustly upregulated by exogenous stressors. Limiting CD47 signalling improved markers of senescence, apoptosis, endoplasmic reticulum stress, unfolded protein response, self-renewal and autophagy, and maintained insulin secretory responses. We also found concurrent upregulated expression of CD47 and senescence markers in the endocrine pancreas of aged donors and those with type 2 diabetes. Both CD47 and TSP1 expression were increased in pancreases of humans with type 1 diabetes, as were plasma levels of TSP1.

CONCLUSIONS/INTERPRETATION: Our study provides key insights into the essential role of CD47 as a novel regulator of islet dysfunction, regulating cytoprotective responses to stress. CD47 may contribute to beta cell damage during the development of diabetes and failure of islet transplant function. Therefore, limiting CD47 activation may be a potential therapeutic tool in conditions where islet function is inadequate.

PMID:40133488 | DOI:10.1007/s00125-025-06409-3

Cells. 2025 Mar 13;14(6):427. doi: 10.3390/cells14060427.

ABSTRACT

This study explores the endocrine-disrupting effects of climbazole (CBZ), an environmental and lifestyle stressor, on male fertility. The impact of CBZ on sperm vitality, motility, and molecular pathways related to hormone receptors and apoptosis was evaluated, in non-capacitated and capacitated conditions. Gene expression of key components, including hormone receptors (ESR1, ESR2, FSHR, AR), apoptosis-related genes (BAX, BCL2), and COX4l1 (involved in mitochondrial function), was analyzed. Protein tyrosine phosphorylation, a marker of capacitation, was also examined using immunofluorescence and Western blot analysis. We demonstrated that CBZ significantly reduced sperm vitality at concentrations above 25 µM and motility at 1 and 10 µM in non-capacitated and capacitated conditions. Changes in tyrosine phosphorylation patterns were also observed. Gene expression analysis revealed an upregulation of ESR1, ESR2, FSHR, and BAX, while AR and COX4l1 expression were downregulated. These findings offer new insights into the potential endocrine-disrupting and cytotoxic effects of CBZ, highlighting its potential role in compromising male reproductive health.

PMID:40136676 | PMC:PMC11940937 | DOI:10.3390/cells14060427

Gels. 2025 Mar 5;11(3):180. doi: 10.3390/gels11030180.

ABSTRACT

The comonomer bisphenol A (BPA) finds applications in the plastics industry, where it is used in the production of polycarbonates, plastics, PVC, thermal paper, epoxy and vinyl ester resins, and polyurethane. The water, with which many of these materials come into contact, is one of the main sources of human exposure to BPA. When ingested or touched, BPA can damage organs, disrupt the endocrine and immune systems, generate inflammatory responses, and be involved in genotoxic processes. Therefore, the need to develop effective techniques for removing BPA from aqueous environments is imperative. This paper provides a comprehensive review regarding the effective removal of BPA from water, focusing on the performance and adsorption mechanisms of various adsorbents based on chitosan and chitosan composites. The chemical and physical factors, adsorption kinetics and models governing the adsorption process of BPA in chitosan materials are also examined. This review outlines that, despite considerable progress in the absorption of bisphenol using chitosan gels, further research is necessary to assess the efficacy of these adsorbents in treating real wastewater and in large-scale manufacture.

PMID:40136885 | PMC:PMC11942317 | DOI:10.3390/gels11030180

Environ Sci Pollut Res Int. 2025 Mar 25. doi: 10.1007/s11356-025-36278-7. Online ahead of print.

ABSTRACT

The Retinoid X Receptor (RXR) has been identified as a primary target in diverse endocrine disruption processes resulting from exposure to tributyltin (TBT), particularly concerning imposex development in gastropods. Two partial open reading frames encoding RXR were successfully isolated from the marine gastropods Buccinastrum deforme (BgRXR) and Trophon geversianus (TgRXR). These edible species, residing in the same area and exposed to similar environmental pollution conditions in Patagonia, Argentina, display different levels of imposex development. Here, we present a thorough functional characterization of both RXRs, examining their responsiveness and modulation by 9-cis-retinoic acid (9-cis-RA) and TBT. BgRXR and TgRXR exhibited dose-dependent activation by both 9-cis-RA and TBT, in luciferase reporter assays. TgRXR displayed higher transcriptional activation than BgRXR triggered by both tested ligands, whereas only BgRXR was activated by low TBT concentrations. Our findings highlight RXR's role in imposex development, emphasizing the importance of species-specific factors in response to environmental contaminants.

PMID:40128418 | DOI:10.1007/s11356-025-36278-7

Front Immunol. 2025 Mar 10;16:1552150. doi: 10.3389/fimmu.2025.1552150. eCollection 2025.

ABSTRACT

OBJECTIVES: Hepatic osteodystrophy (HOD) is an important public health issue that severely affects human health. The pathogenesis of HOD is complex, and exposure to environmental pollutants plays an important role. Di-(2-ethylhexyl) phthalate (DEHP) is a persistent environmental endocrine toxicant that is present in many products, and the liver is an important target organ for its toxic effects. Our research aimed to investigate the effects of DEHP on HOD, and to reveal the underlying mechanisms and the potential key preventive approaches.

METHODS: The daily intake EDI of DEHP and bone density indicators for men and women from 2009 to 2018 were screened and organized from the NHANES database to reveal the population correlation between EDI and BMD; C57BL/6 female and male mice were selected to construct an animal model of DEHP induced HOD, exploring the fuchtions and mechanisms of DEHP on osteoporosis; the novel small molecule inhibitor imICA was used to inhibit the process of DEHP induced osteoporosis, further exploring the targeted inhibition pathway of DEHP induced HOD.

RESULTS: Male and female populations were exposed to a relatively lower concentration of DEHP, and that only the male population exhibited a negative correlation between DEHP exposure and bone mineral density. An in vivo study confirmed that a low dose of DEHP caused liver lesions, disrupted liver function, and induced osteoporosis in male but not female C57BL/6J mice. Regarding the molecular mechanisms, a low dose of DEHP activated the hepatic 14-3-3η/nuclear factor κB (NF-κB) positive feedback loop, which in turn modified the secretory proteome associated with bone differentiation, leading to HOD. Finally, we revealed that targeting the 14-3-3η/ NF-κB feedback loop using our novel 14-3-3η inhibitor (imICA) could prevent DEHP-induced HOD.

CONCLUSION: A low dose of DEHP activated the hepatic 14-3-3η/ NF-κB positive feedback loop, which in turn modified the secretory proteome associated with bone differentiation and elevated IL-6 and CXCL1 levels, leading to HOD. Targeted 14-3-3η/NF-κB feedback loop using our novel 14-3-3η inhibitor, imICA, prevented DEHP-induced HOD.

PMID:40129988 | PMC:PMC11931061 | DOI:10.3389/fimmu.2025.1552150

Ecotoxicol Environ Saf. 2025 Mar 24;294:118088. doi: 10.1016/j.ecoenv.2025.118088. Online ahead of print.

ABSTRACT

Microcystin-LR's reproductive (reproductive and non-reproductive periods) and transgenerational toxicity in amphibians remains poorly understood. Adult Pelophylax nigromaculatus in reproductive and non-reproductive periods were exposed to MC-LR to investigate whether there are differences in the effects of MC-LR on reproductive endocrinology between reproductive and non-reproductive periods of amphibians. Furthermore, cross-mating experiments between MC-LR-exposed and non-exposed frogs in reproductive periods were conducted to explore transgenerational effects. Compared to P. nigromaculatus without MC-LR exposure, exposure to MC-LR resulted in an increase in testosterone synthesis levels and a decrease in estradiol synthesis levels during the reproductive period, but a decrease in testosterone synthesis levels and an increase in estradiol synthesis levels during the non-reproductive period. High lipid contents in the gonads during the reproductive period substantially enriched MC-LR, increasing DNA damage and methylation levels. This may be the reason for the observed opposite trend in sex hormone synthesis levels compared to the non-reproductive period. Additionally, the hypothalamic-pituitary-gonadal-liver axis in F1 tadpoles was disrupted, leading to gonadal dysgenesis, particularly in the ovaries. The observed transgenerational reproductive toxicity may be attributed to decreased gamete quality, transgenerational transfer of MC-LR, and increased DNA methylation level. This study provides novel insights into the differential reproductive endocrine disruption effects of MC-LR during different periods and highlights its transgenerational reproductive toxicity for the first time, underscoring the need for further research on MC-LR's impact on amphibian population dynamics.

PMID:40132506 | DOI:10.1016/j.ecoenv.2025.118088

Toxicology. 2025 Mar 23:154125. doi: 10.1016/j.tox.2025.154125. Online ahead of print.

ABSTRACT

Parabens are a family of alkyl esters of 4-hydroxybenzoic acid. The most commonly used include methylparaben, ethylparaben, propylparaben, and butylparaben. These compounds have been reported to disrupt the endocrine system and are believed to affect the central nervous, immune, and reproductive systems, as well as lipid homeostasis, glucose levels, and thyroid function. Given these effects, parabens pose potential health risks, including their possible link to conditions like diabesity - a term describing the dual condition of type 2 diabetes mellitus and obesity. This review explores current literature on how parabens may influence key mechanisms in diabesity, such as gluconeogenesis, glycogenolysis, adipogenesis, insulin resistance, and inflammation. Understanding their role in these metabolic pathways is critical for assessing their contribution to the diabesity epidemic and guiding future research for minimizing their harmful health impacts.

PMID:40132785 | DOI:10.1016/j.tox.2025.154125

J Xenobiot. 2025 Mar 9;15(2):41. doi: 10.3390/jox15020041.

ABSTRACT

Bis(4-hydroxyphenyl) methane (BPF), as a bisphenolic compound, has toxic effects on organisms such as endocrine disruption and immobilization of growth and development. This study evaluated the effect concentrations of BPF on Chironomus tentans and investigated the impact of BPF exposure at various sub-lethal concentrations on the growth, development, and reproductive capacity of different instars of C. tentans. The results demonstrated that exposure at concentrations of 2.0, 2.5, 3.0, and 4.0 mg·L^-1 delayed pupation, inhibited the development of imaginal discs, and caused an initial rise followed by a decline in the expression levels of genes related to larval development (ecr, usp, e74). Additionally, exposure at concentrations of 1.0, 1.5, and 2.0 mg·L^-1 led to fluctuations in the expression levels of genes related to adult development and reproduction (ecr, kr-h1, foxo, inr, pdk, akt, and vg) in both female and male adults, with varying degrees of effect. Furthermore, BPF exposure inhibited male fertility, causing significant damage to the gonadal tissues, though it did not affect the final hatching of eggs. These findings indicate that BPF exhibits developmental and reproductive toxicity in C. tentans, with 2.0 mg·L^-1 identified as the lowest effective concentration at which BPF affects pupation in midges.

PMID:40126259 | PMC:PMC11932282 | DOI:10.3390/jox15020041

Environ Health Perspect. 2025 Mar 24. doi: 10.1289/EHP14478. Online ahead of print.

ABSTRACT

BACKGROUND: Zearalenone (ZEN) is an estrogenic mycotoxin ('mycoestrogen') that contaminates global grain crops leading to detectable concentrations of ZEN and its metabolites, including the synthetic version alpha-zearalanol (ZER), in human populations. Despite in vitro and in vivo animal evidence of endocrine disruption by ZEN, there has been limited investigation in humans.

OBJECTIVES: To examine markers of fetal growth following prenatal exposure to ZEN and evaluate the role of the placental efflux transporter BCRP/ABCG2 in protecting against ZEN's potential fetoplacental toxicity.

METHODS: Placentas were collected from participants (n= 271) in the UPSIDE cohort (Rochester, NY, USA). Placental ZEN and its metabolites were analyzed from tissue samples using HPLC-MS. Birthweights and placental weights were obtained from medical records and direct measurement, respectively; fetoplacental weight ratio (FPR) was calculated by dividing birthweight by placental weight. Covariate-adjusted generalized linear regression models were used to examine ZEN, ZER, and total mycoestrogens (sum of ZEN, ZER, and their metabolites) in relation to birth length, birthweight, placental weight and FPR. We additionally stratified models by infant sex and ABCG2 C421A (Q141K) genotype.

RESULTS: Mycoestrogens were detected in 84% of placentas (median ZEN: 0.010 ng/g) and total mycoestrogens were associated with lower FPR (-0.20, 95%CI: -0.32,-0.08), particularly in female infants (-0.31, 95%CI:-0.52,-0.09). Associations with birthweight were inverse and overall nonsignificant. Among the 17% of participants with the reduced function 421A ABCG2 variant (AA or AC), total mycoestrogens were associated with lower birthweight (-113.5g, 95%CI: -226.5, -0.50) whereas, in wild-type individuals, total mycoestrogens were associated with higher placental weight (9.9, 95% CI: 0.57, 19.2) and reduced FPR (-0.19, 95%CI: -0.33,-0.05).

DISCUSSION: Results from this epidemiological study of prenatal mycoestrogen exposure and perinatal health suggest that mycoestrogens may reduce placental efficiency, resulting in lower birthweight, particularly in female and ABCG2 421A infants. https://doi.org/10.1289/EHP14478.

PMID:40126888 | DOI:10.1289/EHP14478

Diabetes Metab. 2025 Mar 22;51(3):101641. doi: 10.1016/j.diabet.2025.101641. Online ahead of print.

ABSTRACT

Glucagon-like peptide-1 (GLP-1) is an incretin hormone, secreted from gut endocrine cells, which acts to potentiate nutrient-induced insulin secretion. Activation of its receptor, GLP-1R, decreases glucagon secretion and gastric emptying, thereby decreasing blood glucose and body weight. It is largely through these mechanisms that Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have transformed the treatment of type 2 diabetes. More recently, preclinical and clinical studies have reported that these agents have potent extra-pancreatic effects, exhibiting cardioprotective and renoprotective actions. The recent FLOW trial was the first multicentre clinical trial investigating the effect of GLP-1RAs on a primary renal outcome and reported robust evidence that GLP-1RAs are renoprotective. Studies in rodent models of renal injury have shown that gain and loss of GLP-1R signalling improves or deteriorates kidney function. However, the precise mechanisms responsible for renal benefits of GLP-1RAs are not yet fully understood. While prolonged activation of GLP-1 receptors (GLP-1R) has been shown to reverse diabetes-related disruptions in gene expression across various renal cell populations, GLP-1R expression in both rodent and human kidneys is thought to be primarily confined to certain vascular smooth muscle cells. This review discusses recent advances in our understanding of the effects of GLP-1 medicines on the kidney with a focus on indirect and direct mechanisms of action.

PMID:40127835 | DOI:10.1016/j.diabet.2025.101641

Neurotox Res. 2025 Mar 24;43(2):17. doi: 10.1007/s12640-025-00741-7.

ABSTRACT

Commercial decabromodiphenyl ether (c-decaBDE) is a widely used additive flame retardant in textiles and plastics. This formulation predominantly consists of the congener BDE-209, with trace amounts of other brominated diphenyl ether congeners, such as nonabromodiphenyl ether and octabromodiphenyl ether. Recognized as a persistent organic pollutant due to its potential for long-range environmental transport, c-decaBDE poses significant environmental threats and serious human health risks, including endocrine, reproductive, developmental, and neurotoxic effects. The mechanisms underlying its neurotoxicity remain largely undefined. This study investigates the neurotoxic effects of BDE-209 in humans through network toxicology, multi-level bioinformatics approaches, and molecular docking analyses. Prediction results indicate that BDE-209 can cross the blood-brain barrier, entering the central nervous system and inducing neurotoxic effects. A comprehensive analysis has identified 294 potential targets linked to the neurotoxicity induced by BDE-209. Gene-gene interaction and pathway enrichment analyses revealed significant associations related to cellular responses to chemical stress and synaptic transmission. Further investigation of protein-protein interactions, combined with centrality analysis, identified 14 hub targets, including CaMK-II alpha, PSD-95, GluR-1, and GluN2B, as key proteins in this process. Molecular docking results indicate that BDE-209 exhibits a stronger binding affinity to GluN2B, a subunit of the N-methyl-D-aspartate (NMDA) receptors, compared to other key targets. These findings suggest that BDE-209 may disrupt the function of GluN2B-containing NMDA receptors, potentially leading to their inhibition. Such inhibition could result in reduced excitatory neurotransmission, impairing synaptic potentiation and plasticity, and ultimately contributing to neurotoxicity.

PMID:40123016 | PMC:PMC11930881 | DOI:10.1007/s12640-025-00741-7

Environ Sci Technol. 2025 Mar 24. doi: 10.1021/acs.est.4c13355. Online ahead of print.

ABSTRACT

Exposure to endocrine disrupting chemicals (EDCs), particularly benzophenone (BP)-type UV filters, has been epidemiologically linked to endometrium-related reproductive risks in women. However, their effects on hormone-driven endometrial events and key receptor signaling at the human cellular level remain unexplored. Herein, using human primary endometrial stromal cells (HESCs), we investigated the disrupting effects of five BP congeners and deciphered the underlying mechanism on decidualization, a functional change of the endometrium preparing for pregnancy. BP-8, its two metabolites, BP-3, and BP-1 at 10 nM significantly disrupted progesterone-dependent decidualization in HESCs, marked by 1.5-1.8-fold and 2.2-2.6-fold upregulation of IGFBP-1 and LEFTY, respectively. Decidual transcriptional activators, WNT-FOXO1, were significantly induced by BPs, which are implicated in G2 phase cell arrest (from 3.26% to 8.93%) and apoptosis (from 12.29% to 25.61%). Mechanistically, the inhibition of estrogen receptor α (ERα) effectively alleviated these decidual disrupting effects. BPs increased the transcription of ERα and progesterone receptor (PR) signaling and enhanced nuclear translocation and interaction between ERα and PR during decidualization. The ERα-mediated enhancement of PR signaling activity by BPs was further validated in progesterone response element-luciferase transfected cells. Collectively, our findings elucidate the molecular pathway through which BPs disrupt endometrial decidualization via ERα/PR/FOXO1, providing critical mechanistic insights for the reproductive risk assessment of BPs and structurally related EDCs.

PMID:40127073 | DOI:10.1021/acs.est.4c13355

Environ Health. 2025 Mar 22;24(1):12. doi: 10.1186/s12940-025-01164-9.

ABSTRACT

INTRODUCTION: Long-term endocrine and metabolic health risks associated with oil spill cleanup exposures are largely unknown, despite the endocrine-disrupting potential of crude oil and oil dispersant constituents. We aimed to investigate risks of longer-term endocrine and metabolic conditions among U.S. Coast Guard (USCG) responders to the Deepwater Horizon (DWH) oil spill.

METHODS: Our study population included all active duty DWH Oil Spill Coast Guard Cohort members (N = 45,224). Self-reported spill exposures were ascertained from post-deployment surveys. Incident endocrine and metabolic outcomes were defined using International Classification of Diseases (9th Revision) diagnostic codes from military health encounter records up to 5.5 years post-DWH. Using Cox proportional hazards regression, we estimated adjusted hazard ratios (aHR) and 95% confidence intervals (CIs) for various incident endocrine and metabolic diagnoses (2010-2015, and separately during 2010-2012 and 2013-2015).

RESULTS: The mean baseline age was 30 years (~ 77% white, ~ 86% male). Compared to non-responders (n = 39,260), spill responders (n = 5,964) had elevated risks for simple and unspecified goiter (aHR = 2.09, 95% CI: 1.29-3.38) and disorders of lipid metabolism (aHR = 1.09, 95% CI: 1.00-1.18), including its subcategory other and unspecified hyperlipidemia (aHR = 1.10, 95% CI: 1.01-1.21). The dysmetabolic syndrome X risk was elevated only during 2010-2012 (aHR = 2.07, 95% CI: 1.22-3.51). Responders reporting ever (n = 1,068) vs. never (n = 2,424) crude oil inhalation exposure had elevated risks for disorders of lipid metabolism (aHR = 1.24, 95% CI: 1.00-1.53), including its subcategory pure hypercholesterolemia (aHR = 1.71, 95% CI: 1.08-2.72), the overweight, obesity and other hyperalimentation subcategory of unspecified obesity (aHR = 1.52, 95% CI: 1.09-2.13), and abnormal weight gain (aHR = 2.60, 95% CI: 1.04-6.55). Risk estimates for endocrine/metabolic conditions were generally stronger among responders reporting exposure to both crude oil and dispersants (vs. neither) than among responders reporting only oil exposure (vs. neither).

CONCLUSION: In this large cohort of active duty USCG responders to the DWH disaster, oil spill cleanup exposures were associated with elevated risks for longer-term endocrine and metabolic conditions.

PMID:40121483 | PMC:PMC11929317 | DOI:10.1186/s12940-025-01164-9

Environ Pollut. 2025 Mar 21;373:126103. doi: 10.1016/j.envpol.2025.126103. Online ahead of print.

ABSTRACT

The fluctuation of endocrine hormones during early pregnancy plays an important role in the pathogenesis of hyperemesis gravidarum (HG). As an endocrine disrupting chemical (EDC), perfluoroalkyl substances (PFASs) exert an impact on pregnancy-related complications by altering hormone balances throughout gestation. Despite this potential impact, the relationship between serum PFAS levels in early pregnancy and the risk of HG has not been previously investigated. A total of 98 HG cases and 495 controls were included in this study from the Xi'an Birth Cohort Study. In total, serum levels of 10 PFASs were measured using High Performance Liquid Chromatography with tandem Mass Spectrometry (HPLC-MS/MS) during early pregnancy. Binary logistic models were applied to evaluate the associations between individual PFAS levels and HG. Weighted quantile sum (WQS) regression models and Bayesian kernel machine regression (BKMR) models were performed to test the overall effect of the PFAS mixture on HG. After adjusting for confounding variables, the highest tertile concentrations of perfluoroundecanoic acid (PFUnDA) (OR: 3.49, 95 %CI: 1.31-9.29), and perfluorododecanoic acid (PFDoA) (OR: 3.13, 95 % CI: 1.40-6.98) were significantly associated with a higher risk of HG, while highest tertile of perfluorohexanoic acid (PFHxA) (OR: 0.34; 95 % CI: 0.16-0.73), and PFOS (OR: 0.35; 95 % CI: 0.13-0.97) were inversely associated with HG. The WQS index showed a positive correlation with HG risk (β = 0.80; 95 % CI: 0.02, 1.57), with notable contributions from PFDoA (0.952), PFUnDA (0.159), and perfluorobutanoic acid (PFBA) (0.146). In addition, the joint effect of the PFAS mixture was positively associated with HG, with PFDoA (posterior inclusion probability (PIP) = 0.78) and PFUnDA (PIP = 0.75) being identified as the primary contributors. Our findings indicate that exposure to PFAS mixture during early pregnancy was associated with an increased risk of HG, with PFDoA and PFUnDA being the major contributors.

PMID:40122330 | DOI:10.1016/j.envpol.2025.126103

Food Chem Toxicol. 2025 Mar 21;200:115404. doi: 10.1016/j.fct.2025.115404. Online ahead of print.

ABSTRACT

Breast cancer is the most common neoplasm in women worldwide, with both genetic and environmental factors playing a role in its development. Glyphosate, the active ingredient in widely used agricultural herbicides, is recognized as a potential carcinogen and endocrine disruptor, making it a candidate for inducing epigenetic modifications linked to breast cancer. This study investigates the effects of the glyphosate-based herbicide Roundup® on non-tumorigenic (MCF10A) and tumorigenic (MCF7 and MDA-MB-231) breast cell lines, focusing on the expression of key breast cancer-related genes. Additionally, the study examines the association with epigenetic modifications and the use of epidrugs to reverse potential alterations, aiming to understand the risks and mechanisms of herbicide action. Results indicate that Roundup® affects cells through a non-estrogenic mechanism, impacting both hormone-dependent and -independent cells with varying toxic and proliferative effects depending on dose and exposure time. Moreover, it altered the expression of breast cancer-related genes such as BRCA1 and BRCA2 at low doses. The use of epigenetic modulators was able to reverse some Roundup®-induced changes, suggesting the herbicide's role in epigenetic modifications. Overall, these findings highlight the importance of understanding glyphosate-based herbicide mechanisms in humans, which could enable personalized prevention strategies to mitigate breast cancer risks.

PMID:40122508 | DOI:10.1016/j.fct.2025.115404

Food Chem Toxicol. 2025 Mar 22;200:115391. doi: 10.1016/j.fct.2025.115391. Online ahead of print.

ABSTRACT

We validated the reproducibility and accuracy of a previously developed assay for screening endocrine-disrupting chemicals (EDCs) based on estrogen receptor (ER) dimerization (α-α/α-β/β-β), following OECD GD34 guidelines, to assess its applicability across various laboratories. The inter- and intra-laboratory accuracy was evaluated using 22 validation substances (ICCVAM-recommended substances for validating in vitro ER-binding assays) with confirmed estrogenic activity in four independent laboratories. Intra-laboratory reproducibility for 22 chemicals was at least 95.5 % for ER α-α and β-β and 100 % for ER α-β, with mean values of 98.9 % (ER α-α), 100 % (ER α-β), and 98.9 % (ER β-β), respectively. The inter-laboratory qualitative reproducibility for ER α-α, ER α-β, and ER β-β was 100 %, 100 %, and 95.5 %, respectively. The validated results for the ER dimerization (α-α/α-β/β-β) assays were compared with the results (17 test chemicals) from the National Toxicology Program Interagency Center for Evaluation of Alternative Toxicological Methods (NICEATM), confirming the validity of the assay. The accuracies for ER α-α, α-β, β-β dimerization in cell were 88.2 %, 94.1 %, 88.2 %, respectively. Thus, ER dimerization assays demonstrated high intra- and inter-laboratory reproducibility and accuracy through this validation study. This suggests that the assay is a robust method for detecting ER dimerization within cells.

PMID:40122509 | DOI:10.1016/j.fct.2025.115391

Environ Pollut. 2025 Mar 21;373:126103. doi: 10.1016/j.envpol.2025.126103. Online ahead of print.

ABSTRACT

The fluctuation of endocrine hormones during early pregnancy plays an important role in the pathogenesis of hyperemesis gravidarum (HG). As an endocrine disrupting chemical (EDC), perfluoroalkyl substances (PFASs) exert an impact on pregnancy-related complications by altering hormone balances throughout gestation. Despite this potential impact, the relationship between serum PFAS levels in early pregnancy and the risk of HG has not been previously investigated. A total of 98 HG cases and 495 controls were included in this study from the Xi'an Birth Cohort Study. In total, serum levels of 10 PFASs were measured using High Performance Liquid Chromatography with tandem Mass Spectrometry (HPLC-MS/MS) during early pregnancy. Binary logistic models were applied to evaluate the associations between individual PFAS levels and HG. Weighted quantile sum (WQS) regression models and Bayesian kernel machine regression (BKMR) models were performed to test the overall effect of the PFAS mixture on HG. After adjusting for confounding variables, the highest tertile concentrations of perfluoroundecanoic acid (PFUnDA) (OR: 3.49, 95 %CI: 1.31-9.29), and perfluorododecanoic acid (PFDoA) (OR: 3.13, 95 % CI: 1.40-6.98) were significantly associated with a higher risk of HG, while highest tertile of perfluorohexanoic acid (PFHxA) (OR: 0.34; 95 % CI: 0.16-0.73), and PFOS (OR: 0.35; 95 % CI: 0.13-0.97) were inversely associated with HG. The WQS index showed a positive correlation with HG risk (β = 0.80; 95 % CI: 0.02, 1.57), with notable contributions from PFDoA (0.952), PFUnDA (0.159), and perfluorobutanoic acid (PFBA) (0.146). In addition, the joint effect of the PFAS mixture was positively associated with HG, with PFDoA (posterior inclusion probability (PIP) = 0.78) and PFUnDA (PIP = 0.75) being identified as the primary contributors. Our findings indicate that exposure to PFAS mixture during early pregnancy was associated with an increased risk of HG, with PFDoA and PFUnDA being the major contributors.

PMID:40122330 | DOI:10.1016/j.envpol.2025.126103

Environ Monit Assess. 2025 Mar 21;197(4):456. doi: 10.1007/s10661-025-13809-w.

ABSTRACT

Wastewater is a major source of contamination and must be treated before it is discharged into rivers and lakes. Water contaminated with emerging pollutants such as micropollutants, pharmaceuticals, endocrine disruptors (EDs), pesticides, synthetic dyes, toxins and hormones is of major concern due to its potential adverse effects. The accumulation of such pollutants can disbalance trophic levels and has negative ecological impacts and possible health risks. Monitoring and detecting these contaminants is essential for effective mitigation. Ongoing research on emerging contaminants drives the development of new analytical techniques and technologies for detection, monitoring and removal of such contaminants. As the demand for sustainable wastewater management increases, both conventional and advanced detection methods can be practised as treatment strategies. This approach enhances our capacity to detect and measure contaminants in environmental samples, leading to the development of more effective treatment methods. This review provides important insights into different classes of emerging contaminants, their sources as well as environmental and health risks associated with these pollutants. It also examines the major conventional and advanced technologies used to manage emerging contaminants.

PMID:40119196 | DOI:10.1007/s10661-025-13809-w

Environ Monit Assess. 2025 Mar 22;197(4):457. doi: 10.1007/s10661-025-13896-9.

ABSTRACT

The current work gives a snapshot of pesticide residuals, their exposure levels, and the associated potential risks of some organophosphates in Coimbatore district, Tamil Nadu. The study has significant viewpoints on food safety and pesticide management. The pesticide residual analysis was carried out on two commonly used vegetables, tomato and brinjal. The QuEChERS method is used to extract pesticides and GC-MS/SIM analyses were used to quantify pesticide residues. Among the various samples tested, organophosphorus pesticides, such as Phorate Sulfoxide, Chlorpyrifos, and Malathion, were detected in some samples. In the majority of brinjal samples analyzed, no pesticide residues were detected. However, one sample showed the presence of malathion (0.001 mg/kg). The detected level of malathion was within the acceptable safety limits, indicating that the sample is safe for consumption. Nevertheless, in one of the tomato samples tested, the residual level of phorate sulfoxide (0.34 mg/kg) is found to be higher than the MRL with a health risk index of 2.79. Except for phorate sulfoxide, all the other pesticide residuals were within MRL. Phorate residues with a soil half-life of 2 to 173 days are readily water soluble and may leach easily into groundwater, adversely affecting human health. The dietary risk of phorate can also put people at increased health risks of reproductive harm, endocrine system disruption, neurological damage, and an increased risk of certain cancers. The study's outcome suggests the need to review the strict guidelines imposed on using unsafe pesticides. Also, future investigations are necessary to validate the presence of other toxic pesticides in the study area.

PMID:40119213 | DOI:10.1007/s10661-025-13896-9

J Hazard Mater. 2025 Mar 18;491:137961. doi: 10.1016/j.jhazmat.2025.137961. Online ahead of print.

ABSTRACT

Tetrabromobisphenol A (TBBPA), a most widely used brominated flame retardant, has been detected in worldwide aquatic environments. However, the effects and mechanisms of TBBPA at environmentally realistic levels have not been well characterized in aquatic organisms. This study aims to investigate the impact of TBBPA on developmental toxicity and endocrine system in two generations of marine medaka (Oryzias melastigma) during early life stages. The results revealed that the embryos under exposure to environmentally relevant concentrations of TBBPA (0, 5, 50, and 500 μg/L) resulted in accelerated hatching and growth development in F0 generation. Conversely, delayed hatching, decreased hatch rate, and growth inhibition were observed in the F1 generation. Moreover, TBBPA disrupted the levels of THs (thyroid hormones), GH (growth hormone), and IGF (insulin growth factor). The gene transcriptional profiling implies modified gene expressions in the HPT axis, GH/IGF axis, and endoplasmic reticulum stress. The molecular docking analysis confirmed the binding affinity of TBBPA to key endocrine-related proteins, which partially elucidates the mechanism of endocrine disruption and developmental abnormalities. Endoplasmic reticulum stress may explain the developmental differences between the two generations. This was the first study to explore the multigenerational developmental toxicity of TBBPA to marine fish, which is essential for ecological risk assessment of this emerging pollutant.

PMID:40120263 | DOI:10.1016/j.jhazmat.2025.137961

Mar Pollut Bull. 2025 Mar 21;215:117840. doi: 10.1016/j.marpolbul.2025.117840. Online ahead of print.

ABSTRACT

Antibiotics and endocrine-disrupting chemicals (EDCs) were measured near a juvenile Chinese sturgeon habitat (JCSH) in the Yangtze River Estuary. It was found that the concentrations in the wet season, when Chinese sturgeon are frequently detected in the habitat, were 146 ± 140 ng/L and 2.34 ± 1.50 ng/L. They posed a high/medium risk to algae and fish. Mega-cities surround the habitat. The largest one, Shanghai, discharges 1020 kg antibiotics and 42.3 kg EDCs to the waterbody near the habitat annually. Restrictions on antibiotic use and industrial restructuring cannot efficiently reduce these pollutants. Optimization of wastewater treatment processes regarding antibiotics and EDCs is necessary. To keep the effluent safe for algae and fish, the removal rate of the risky substances sulfonamides (SAs), fluoroquinolones (FQs), phenolic estrogens (PEs), and steroid estrogens (SEs) should be elevated to 77 %, 99 %, 99 %, and 89 %. Advanced oxidation or adsorption should be added to promote the environmental quality of the JCSH.

PMID:40120357 | DOI:10.1016/j.marpolbul.2025.117840

Sci Rep. 2025 Mar 21;15(1):9810. doi: 10.1038/s41598-025-93538-9.

ABSTRACT

Bisphenol A (BPA), widely used in plastic production, acts as an environmental endocrine disruptor which is harmful to male reproductive health. However, the specific mechanisms through which prenatal BPA exposure disrupts spermatogenesis in offspring, particularly in terms of Leydig cell dysfunction and meiotic progression, remain poorly understood. To address this gap, we constructed a mouse model with BPA lowest Observed Adverse Effect Level (LOAEL: 50 mg/kg bw/day) exposure from embryonic day (ED) 0.5 to 18.5. Our results demonstrated that prenatal BPA exposure significantly decreased serum testosterone levels, testis weight, sperm count, motility parameters, and acrosomal integrity. Furthermore, it arrested the meiotic transition from zygotene to pachytene spermatocytes, leading to reduced sperm fertility characterized by reduced sperm-egg binding capacity and abnormal early embryonic cleavage in the male offspring. Importantly, prenatal BPA exposure significantly reduced the expression of PCNA (a marker of germ cell proliferation), SYCP3 (a meiosis regulator), and Vimentin (a blood-testis barrier component), collectively indicating impaired spermatogenesis in offspring testes. Additionally, prenatal BPA exposure dramatically reduced Leydig cell numbers and increased apoptosis, marked by BAX/BCL2 up-regulation, which mechanistically explains the observed testosterone reduction. In vitro experiments corroborated these effects: BPA exposure concentration-dependently inhibited Leydig cell proliferation, induced G0/G1 phase arrest, and downregulated testosterone synthesis molecules (Hsd3b1, Hsd17b3, Star, Cyp11a1, Cyp17a1). Quantitative proteomics identified 234 differentially expressed proteins (97 downregulated, 137 upregulated) in BPA-exposed Leydig cells. Bioinformatics analysis revealed that down-regulated proteins were mainly related to steroid hormone receptor activity, estrogen response element binding, and centrosome duplication processes, while the up-regulated proteins were mainly involved in oxygen binding and ROS metabolic process. Conclusively, prenatal BPA exposure impaired offspring male fertility via multi-faceted mechanisms: sperm quality defects, steroidogenic disruption, and meiotic arrest. This study advances the understanding of BPA transgenerational reproductive toxicity and underscores the need to mitigate prenatal exposure risks.

PMID:40118943 | PMC:PMC11928659 | DOI:10.1038/s41598-025-93538-9

J Hazard Mater. 2025 Mar 17;491:137947. doi: 10.1016/j.jhazmat.2025.137947. Online ahead of print.

ABSTRACT

Alternative phthalates (APs) have been developed due to the reported adverse effects of conventional phthalates (CPs). However, whether APs are nontoxic and can replace CPs remains controversial due to their endocrine-disrupting (ED) effects. Herein, to investigate the ED potential of diethyl-hexyl-cyclohexane (DEHCH), a newly developed non-phthalate-structured AP, we employed in silico (molecular docking simulation), in vitro (cell-based assays for estrogen and androgen receptors), and in vivo (zebrafish embryo model) methods. We also compared the results with two CPs (di(2-ethylhexyl) phthalate [DEHP] and diisononyl phthalate [DINP]) and two previously proposed non-phthalate-structured APs (1,2-cyclohexane dicarboxylic acid diisononyl ester [DINCH] and di-2-ethylhexyl terephthalate [DEHTP]). DEHCH did not exhibit the highest binding affinity for any of the five receptors such as estrogen, androgen, glucocorticoid receptors, and thyroid receptor alpha and beta. None of the tested phthalates exhibited agonistic or antagonistic effects on estrogen and androgen receptors. In zebrafish larvae, DEHCH did not affect the expression of the nine endocrine-related genes and neurobehaviors, which correlates well with the lack of changes in the endogenous concentrations of the five neurosteroids. In contrast, DINCH, DEHP, and DEHTP induced hyperactivity, and except for DEHCH, four phthalates significantly upregulated at least one gene. In addition, DINCH significantly increased the expression of cortisol and DEHP increased progesterone, allopregnanolone, and cortisol. These findings demonstrate that DEHCH is safer than CPs and the previously proposed APs in terms of ED effects, including neuronal system dysregulation.

PMID:40117772 | DOI:10.1016/j.jhazmat.2025.137947

Semin Liver Dis. 2025 Mar 21. doi: 10.1055/a-2540-2861. Online ahead of print.

ABSTRACT

Environmental pollutants significantly impact liver disease development, progression, and outcomes. This review examines the complex relationship between environmental exposures and liver pathology, from malignant conditions like hepatocellular carcinoma to steatotic and cholestatic liver diseases. Key environmental factors include air pollutants, volatile organic compounds, persistent organic pollutants, heavy metals, and per- and polyfluoroalkyl substances. These compounds can act through multiple mechanisms, including endocrine disruption, metabolic perturbation, oxidative stress, and direct hepatotoxicity. The impact of these exposures is often modified by factors such as sex, diet, and genetic predisposition. Recent research has revealed that even low-level exposures to certain chemicals can significantly affect liver health, particularly when combined with other risk factors. The emergence of exposomics as a research tool promises to enhance our understanding of how environmental factors influence liver disease. Importantly, exposure effects can vary by demographic and socioeconomic factors, highlighting environmental justice concerns. Implementation of this knowledge in clinical practice requires new diagnostic approaches, healthcare system adaptations, and increased awareness among medical professionals. In conclusion, this review provides a comprehensive examination of current evidence linking environmental exposures to liver disease and discusses implications for clinical practice and public health policy.

PMID:40118102 | DOI:10.1055/a-2540-2861

Ecotoxicol Environ Saf. 2025 Mar 20;294:118077. doi: 10.1016/j.ecoenv.2025.118077. Online ahead of print.

ABSTRACT

BACKGROUND: Endocrine-disrupting chemicals (EDCs) can disturb lipid and glucose metabolism, but few studies have explored the effects of EDC mixtures and underlying inflammation mechanisms in weight-specific children.

METHODS: We conducted a panel study with 3 repeated visits among 144 children aged 4-12 years. For each visit, participants provided morning urine samples for 4 consecutive days and fasting blood samples on day 4. A total of 36 EDCs were measured, including 10 per- and polyfluoroalkyl substances (PFAS), 3 phenols, 3 parabens, 10 phthalates, and 10 polycyclic aromatic hydrocarbons. We used quantile g-computation, grouped weighted quantile sum (GWQS) regression, and linear mixed-effect models to evaluate and validate the associations of the mixture and individual effects of EDCs on lipid and fasting blood glucose (FBG). Further, mediation models were applied to explore the potential role of cytokines in the relationships of EDCs and outcomes.

RESULTS: A quantile increase in EDC mixtures was associated with elevated triglyceride (TG) (β = 0.18, 95 % CI: 0.04, 0.33) and FBG (β = 0.02, 95 % CI: 0.01, 0.04). Also, GWQS regression revealed that PFAS contributed the most to the overall effects for TG and FBG, followed by phenols. These associations were more pronounced in overweight/obese children. Regarding individual pollutants, we observed positive relationships of several PFAS with TG and FBG. Furthermore, chemokine ligand 2 mediated the associations of PFAS with TG among overweight/obese children.

CONCLUSIONS: The present study suggested that the EDC mixtures were associated with elevated lipid and glucose levels among children, particularly for those with overweight/obesity.

PMID:40118019 | DOI:10.1016/j.ecoenv.2025.118077

Environ Res. 2025 Mar 19;275:121439. doi: 10.1016/j.envres.2025.121439. Online ahead of print.

ABSTRACT

BACKGROUND AND AIM: The relationship between prenatal exposure to per- and polyfluoroalkyl substances (PFASs), a well-known endocrine disruptor, and thyroid hormones (THs) levels remains unclear. Therefore, this study aimed to investigate this relationship in a birth cohort during the second trimester.

METHOD: This prospective study included 562 pregnant women in the Wuxi Birth Cohort from 2019 to 2021 and quantified the serum concentrations of 23 PFASs and 5 THs. Multiple statistical models were used to assess the associations between individual or combined PFASs concentrations and THs, while molecular docking simulated the interactions between PFASs and four thyroid-related proteins.

RESULTS: The median concentration of ∑₂₃PFASs was 71.91 ng/mL, with perfluorovaleric acid (PFPeA) (18.13 ng/mL) emerging as the predominant PFAS. Most PFASs were negatively associated with maternal free thyroxine (FT4) and thyroid-stimulating hormone (TSH) levels, whereas perfluorobutane sulfonate (PFBS) was positively correlated with TSH levels. A similar trend was observed in the weighted quantile sum (WQS) model, in which combined PFASs exposure was inversely associated with the FT4 and TSH levels. Molecular docking results showed that compared with TH natural ligand thyroxine (T4), perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl- PFESA) exhibited relatively high binding affinity with thyroid-related proteins (-6.6 to -9.8 kcal/mol vs. T4: -5.6 to -8.6 kcal/mol). Furthermore, PFASs with medium chain lengths and sulfonic acid groups exhibited enhanced protein-binding properties.

CONCLUSION: PFASs exposure may affect THs homeostasis during pregnancy. Moreover, different types and concentrations of PFASs have different effects on THs in the maternal serum.

PMID:40118311 | DOI:10.1016/j.envres.2025.121439

Environ Res. 2025 Mar 19;276:121438. doi: 10.1016/j.envres.2025.121438. Online ahead of print.

ABSTRACT

BACKGROUND: The role of endocrine disrupting chemicals (EDCs) in the development of metabolic syndrome has gained increasing recognition in recent years. The underlying mechanisms are largely unresolved. Disruption of corticosteroid action and hypothalamic-pituitary-adrenal (HPA) axis are considered possible mechanisms.

OBJECTIVE: To summarise epidemiological studies investigating an association between EDC concentration and altered levels of corticosteroids and the adrenocorticotropic hormone (ACTH).

METHODS: Following the PRISMA guidelines, we searched PubMed and the Cochrane Library for epidemiological studies published from database inception until April 1st, 2024. Various groups of EDCs were evaluated with the prerequisite of direct measurement of the chemical, a metabolite, or biomarker.

RESULTS: We identified 2094 articles. After removing duplicates and screening, 27 studies were included. Studies focused predominantly on glucocorticoids (n = 26) compared to mineralocorticoids (n = 5) and ACTH (n = 2). The most studied EDCs were pesticides (n = 9) and phthalates (n = 8). Significant associations between the concentrations of specific EDCs and hormone levels were found in all but three studies. Only one study described an association between EDCs, and hormone concentration and metabolic features.

CONCLUSION: There is clear evidence for the impact of specific EDCs on plasma corticosteroid concentrations in different age groups worldwide, however, results varied according to EDC class, study population and study methodology. Further research combining EDC and hormone concentrations, and clinical features, complemented by experimental investigations to study cell mechanisms, is needed to gain holistic knowledge of EDCs' influence on glucocorticoid- and mineralocorticoid-related disorders.

PMID:40118322 | DOI:10.1016/j.envres.2025.121438

Environ Pollut. 2025 Mar 19;373:126086. doi: 10.1016/j.envpol.2025.126086. Online ahead of print.

ABSTRACT

The presence of phenolic endocrine disrupting chemicals (EDCs) in patients with secondary non-alcoholic fatty liver disease (S-NAFLD) and their associations with S-NAFLD incidence have not been previously documented. In this study, serum concentrations of 32 phenolic EDCs, including parabens, benzophenone-type UV-filters, bisphenols, and bisphenol A diglycidyl ether derivatives, were detected in patients with S-NAFLD as well as healthy population from South China. These target EDCs were ubiquitous in serum samples from both cohorts. Interestingly, significantly higher (p < 0.05) serum levels of most analytes were detected in individuals with S-NAFLD compared to those in the healthy population. Through multiple modeling analyses, we observed that parabens and bisphenols mixtures were positively associated with S-NAFLD incidence. A list of high-risk EDCs for S-NAFLD-related diseases was identified, including propyl paraben (PrP), butyl paraben (BuP), bisphenol A (BPA), and bisphenol AP (BPAP). Furthermore, significant positive correlations were found between the serum levels of these high-risk analytes and liver clinic indices. To the best of our knowledge, this study firstly examined the serum levels of multiple phenolic EDCs in patients with S-NAFLD, aiming to provide novel insights into high-risk EDCs associated with S-NAFLD incidence and their associations with clinic liver indices.

PMID:40118363 | DOI:10.1016/j.envpol.2025.126086

Ecotoxicol Environ Saf. 2025 Mar 20;294:118077. doi: 10.1016/j.ecoenv.2025.118077. Online ahead of print.

ABSTRACT

BACKGROUND: Endocrine-disrupting chemicals (EDCs) can disturb lipid and glucose metabolism, but few studies have explored the effects of EDC mixtures and underlying inflammation mechanisms in weight-specific children.

METHODS: We conducted a panel study with 3 repeated visits among 144 children aged 4-12 years. For each visit, participants provided morning urine samples for 4 consecutive days and fasting blood samples on day 4. A total of 36 EDCs were measured, including 10 per- and polyfluoroalkyl substances (PFAS), 3 phenols, 3 parabens, 10 phthalates, and 10 polycyclic aromatic hydrocarbons. We used quantile g-computation, grouped weighted quantile sum (GWQS) regression, and linear mixed-effect models to evaluate and validate the associations of the mixture and individual effects of EDCs on lipid and fasting blood glucose (FBG). Further, mediation models were applied to explore the potential role of cytokines in the relationships of EDCs and outcomes.

RESULTS: A quantile increase in EDC mixtures was associated with elevated triglyceride (TG) (β = 0.18, 95 % CI: 0.04, 0.33) and FBG (β = 0.02, 95 % CI: 0.01, 0.04). Also, GWQS regression revealed that PFAS contributed the most to the overall effects for TG and FBG, followed by phenols. These associations were more pronounced in overweight/obese children. Regarding individual pollutants, we observed positive relationships of several PFAS with TG and FBG. Furthermore, chemokine ligand 2 mediated the associations of PFAS with TG among overweight/obese children.

CONCLUSIONS: The present study suggested that the EDC mixtures were associated with elevated lipid and glucose levels among children, particularly for those with overweight/obesity.

PMID:40118019 | DOI:10.1016/j.ecoenv.2025.118077

Arch Toxicol. 2025 Mar 21. doi: 10.1007/s00204-025-04009-z. Online ahead of print.

ABSTRACT

Neurological disorders have become the leading cause of disease and disability worldwide, with 80% of these conditions being recorded in low- and middle-income countries. Scientific evidence has increasingly associated these disorders with exposure to xenobiotics, such as pesticides, heavy metals and endocrine-disrupting chemicals (EDCs). Recent studies have focused on the consequences of exposure to chemical mixtures and their potential neurotoxic effects. As reported, such exposures can adversely affect cognitive and motor skills, particularly when they occur prenatally or during the early stages of development. Long-term exposure to mixtures of these substances has been strongly related to oxidative stress, inflammation and neurodegeneration. This review aims to explore the neurobehavioral effects of low-dose xenobiotic combinations, stressing the potential long-term neurological damage from such exposure. The in vivo and epidemiological studies reviewed indicate that early-life exposure to chemical mixtures is linked to motor and cognitive disorders, increased anxiety prevalence and behavioral dysregulation. Mechanistic evidence suggests that these exposures may exacerbate oxidative stress, immune activation, and neuronal dysfunction, ultimately leading to neuroinflammation. Chemical interactions greatly affect neurotoxicity, often deviating from simple dose addition. Synergistic effects can arise at both low and high doses, while some studies also report antagonistic outcomes. The specific impacts depend on the chemicals involved, their ratios, and the biological endpoints assessed. Since pollutants like heavy metals can persist in the environment due to their resistance to natural degradation processes, innovative strategies are necessary to mitigate the detrimental effects of exposure to chemical mixtures on human health and the environment.

PMID:40116907 | DOI:10.1007/s00204-025-04009-z

Arch Toxicol. 2025 Mar 21. doi: 10.1007/s00204-025-04025-z. Online ahead of print.

ABSTRACT

Bisphenol A (BPA) is a widely used chemical that is slowly being phased out due to its toxic properties. The industry is therefore looking for alternatives in the form of BPA analogs. However, studies have shown that BPA analogs can have comparable or even stronger endocrine and toxic effects than BPA. This review describes various mechanisms and interactions of BPA analogs with individual nuclear receptors. They interfere with downstream signaling pathways not only by binding to the nuclear receptors, but also by various alternative mechanisms, such as altering receptor expression, affecting co-receptors, altering signal transduction pathways, and even epigenetic changes. Further studies are needed to fully investigate the potential synergistic and additive effects that may result. In the search for a less harmful alternative to BPA, affinity to the nuclear receptor may not be the decisive factor. We therefore recommend a different study approach to assess their effects on the endocrine system before new BPA analogs are introduced to the market to protect public health and the environment.

PMID:40116906 | DOI:10.1007/s00204-025-04025-z

Environ Res. 2025 Mar 19;275:121439. doi: 10.1016/j.envres.2025.121439. Online ahead of print.

ABSTRACT

BACKGROUND AND AIM: The relationship between prenatal exposure to per- and polyfluoroalkyl substances (PFASs), a well-known endocrine disruptor, and thyroid hormones (THs) levels remains unclear. Therefore, this study aimed to investigate this relationship in a birth cohort during the second trimester.

METHOD: This prospective study included 562 pregnant women in the Wuxi Birth Cohort from 2019 to 2021 and quantified the serum concentrations of 23 PFASs and 5 THs. Multiple statistical models were used to assess the associations between individual or combined PFASs concentrations and THs, while molecular docking simulated the interactions between PFASs and four thyroid-related proteins.

RESULTS: The median concentration of ∑₂₃PFASs was 71.91 ng/mL, with perfluorovaleric acid (PFPeA) (18.13 ng/mL) emerging as the predominant PFAS. Most PFASs were negatively associated with maternal free thyroxine (FT4) and thyroid-stimulating hormone (TSH) levels, whereas perfluorobutane sulfonate (PFBS) was positively correlated with TSH levels. A similar trend was observed in the weighted quantile sum (WQS) model, in which combined PFASs exposure was inversely associated with the FT4 and TSH levels. Molecular docking results showed that compared with TH natural ligand thyroxine (T4), perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl- PFESA) exhibited relatively high binding affinity with thyroid-related proteins (-6.6 to -9.8 kcal/mol vs. T4: -5.6 to -8.6 kcal/mol). Furthermore, PFASs with medium chain lengths and sulfonic acid groups exhibited enhanced protein-binding properties.

CONCLUSION: PFASs exposure may affect THs homeostasis during pregnancy. Moreover, different types and concentrations of PFASs have different effects on THs in the maternal serum.

PMID:40118311 | DOI:10.1016/j.envres.2025.121439