Endocrine Disruption

Front Endocrinol (Lausanne). 2025 May 6;15:1430781. doi: 10.3389/fendo.2024.1430781. eCollection 2024.

ABSTRACT

INTRODUCTION: Pregnane X Receptor (PXR, NR1I2) is a ligand-dependent transcription factor belonging to the nuclear receptor superfamily, that can be activated by a wide variety of endogenous and exogenous ligands. It is a major actor of the endo- and xeno-biotic detoxification process. It also regulates biological processes such as lipid metabolism in large number of tissues. Pxr was shown to be expressed in human, mouse, rat and pig testis, however its roles in the regulation of testicular functions have been little explored so far.

METHODS: To determine the potential involvement of PXR in the regulation of steroidogenesis, experiments were performed on a wild type (MLTC-1WT) and a Pxr knock-down (MLTC-1PxrKD) mouse Leydig cell line (MLTC-1 cells), treated with a PXR agonist (SR-12813) in acute and chronic conditions.

RESULTS: Our analyses confirmed the presence of Pxr transcripts in the mouse testis, particularly in Leydig cells. In addition, A lower testosterone concentration was measured in MLTC-1PxrKD cells compared to wild type cells. Moreover, both acute and chronic stimulation of MLTC-1WT cells with SR-12813 led to a decrease in testosterone concentration, associated with a lower expression of some steroidogenic genes. This negative impact of SR-12813 on Leydig cell steroidogenesis was counteracted by Pxr knock down.

DISCUSSION: Overall, these results support the involvement of PXR in the regulation of testosterone homeostasis in mouse Leydig cells and open new avenues of research into the involvement of this receptor in the deleterious effects of certain endocrine disruptors on the steroidogenic activity of Leydig cells.

PMID:40395611 | PMC:PMC12088964 | DOI:10.3389/fendo.2024.1430781

RSC Adv. 2025 May 20;15(21):16690-16707. doi: 10.1039/d5ra01906k. eCollection 2025 May 15.

ABSTRACT

The pervasive presence of endocrine-disrupting chemicals (EDCs), particularly progesterone, in aquatic ecosystems poses significant ecological and human health risks, necessitating the development of sustainable and efficient removal strategies. This study introduces an innovative, eco-friendly approach utilizing non-edible reishi mushroom (Ganoderma lucidum) and its calcined form as natural adsorbents for progesterone removal while simultaneously exploring the potential of the formed composites as sustainable agricultural amendments. The adsorption efficiency of both reishi mushroom powder and its calcined form was systematically optimized under varying pH, adsorbent dose, temperature, and contact time conditions. The adsorption capacities of reishi mushroom and its calcined form for progesterone were assessed using nine non-linear isotherm models. Among these, the Langmuir and Freundlich models provided the best fit to the experimental data (R ² ∼ 0.99), demonstrating high adsorption capacities of 90.52 mg g^-1 for reishi mushroom and 118.10 mg g^-1 for calcined reishi mushroom under optimal conditions (pH 3, 25 °C, 0.1 g and 0.075 g doses, respectively) following pseudo-second-order and mixed-order kinetic models. Both materials were fully characterized before and after the adsorption process using XRD, FTIR, and SEM techniques. Thermodynamic analysis revealed the process to be exothermic, spontaneous, and highly ordered, driven by hydrophobic interactions and van der Waals forces. Molecular docking analysis shows that ganoderic acid A and progesterone bind strongly to key plant hormone receptors (GID1, TIR1, BRI1), indicating their potential to enhance plant growth by influencing gibberellin, auxin, and brassinosteroid signaling pathways. Beyond environmental remediation, the formed composites exhibited exceptional potential in enhancing agricultural productivity. Composite treatments, particularly progesterone adsorbed on calcined reishi mushroom, significantly improved seed germination rates (95%), shoot-to-root elongation (2.5 : 1), and overall plant growth (39 cm height, 200 g fresh weight). Soil quality assessments revealed increased organic matter content and improved fertility, highlighting the dual benefit of these adsorbents in environmental remediation and sustainable agriculture. The greenness profile of the proposed method, evaluated using NEMI, AGP, and Modified GAPI metrics, further underscores its eco-sustainability, with an eco-scale score of 94 and a BAGI blueness score of 75, affirming its alignment with green analytical chemistry principles. This study introduces a novel, cost-effective, and eco-friendly method for progesterone removal while pioneering the use of waste-derived adsorbents in circular agriculture. By utilizing reishi mushroom and its calcined form, this research addresses both water contamination and sustainable farming, advancing eco-friendly technologies.

PMID:40395785 | PMC:PMC12089978 | DOI:10.1039/d5ra01906k

Front Endocrinol (Lausanne). 2025 May 6;16:1551784. doi: 10.3389/fendo.2025.1551784. eCollection 2025.

ABSTRACT

BACKGROUND: Terpenes are potentially harmful substances that are associated with endocrine disruption due to their ability to produce oxidizers, aldehydes, and secondary aerosol particles. However, the exact association between terpenoids and metabolic syndrome remains unclear.

OBJECTIVE: This study aims to examine the relationship between individual and mixed exposure to terpene compounds and the risk of developing metabolic syndrome.

METHODS: We utilized data from the NHANES 2013-2014 cycle, including 1,135 participants. Multiple regression models, Bayesian kernel regression (BKMR), and quantile g calculation (QGC) were employed to assess the association between individual and mixed terpene exposure and metabolic syndrome. Additionally, a mediation analysis was performed to explore potential biological pathways mediated by inflammation, using the Advanced Cancer Inflammation Index as a metric.

RESULTS: The regression analysis indicated a positive association between exposure to limonene and metabolic syndrome (OR (95%):1.74(1.17, 2.57), p=0.005). The BKMR regression and the QGC model showed a positive association between exposure to mixed terpenes and the increased risk of metabolic syndrome (p=0.001). Subgroup analyses within the BKMR revealed significant positive trends among males, individuals under 60, and the overweight groups. Furthermore, exposure to mixed terpenes exhibited positive trends with lower HDL levels(p<0.000). The Advanced Cancer Inflammation Index was identified as a potential mediator of the positive correlation between α-pinene, β-pinene, and metabolic syndrome.

CONCLUSIONS: This study suggests that exposure to both individual and mixed terpenes may increase risk of developing metabolic syndrome. However, further longitudinal studies are imperative to establish causality between terpene compounds and the risk of metabolic syndrome.

PMID:40395814 | PMC:PMC12088976 | DOI:10.3389/fendo.2025.1551784

Int J Hyg Environ Health. 2025 May 19;267:114597. doi: 10.1016/j.ijheh.2025.114597. Online ahead of print.

ABSTRACT

Environmental phenols and phthalates, endocrine-disrupting chemicals, are linked to dietary intake, highlighting the need to identify sources to prevent exposure-related diseases. This study investigates dietary patterns associated with urinary concentrations of environmental phenols and phthalate metabolites in Korean adults using data from 4201 adults in the Korean National Environmental Health Survey Cycle 4 (2018-2020). Exploratory factor analysis identified three dietary patterns: Western-style, traditional Korean, and seafood-rich. We analyzed metabolites with a ≥80 % detection rate, specifically environmental phenols (BPA, BPF, BPS, TCS, MP, EP, BP) and phthalates (MEHHP, MEOHP, MnBP, MECPP, MBzP, MCPP, MEP, MMP). The Western-style or processed food diet showed a significant negative association with MP (β [95 % CI] = -0.14 [-0.24, -0.03]), but no positive association. The traditional Korean diet showed significant positive associations with TCS (β [95 % CI] = 0.09 [0.02, 0.15]), EP (β [95 % CI] = 0.08 [0.01, 0.16]), BP (β [95 % CI] = 0.09 [0.05, 0.12]), MEHHP (β [95 % CI] = 0.04 [0.003, 0.08]), MECPP (β [95 % CI] = 0.06 [0.02, 0.09]), and MMP (β [95 % CI] = 0.11 [0.06, 0.15]). In comparison, it had a significant negative association with BPS (β [95 % CI] = -0.15 [-0.22, -0.09]). The seafood-rich dietary pattern exhibited a significant negative association with BP (β [95 % CI] = -0.07 [-0.11, -0.03]). Certain dietary patterns, including those traditionally regarded as healthy, may be associated with exposure to environmental phenols and phthalates, highlighting the need for further research to understand dietary sources of exposure before drawing implications for public health guidance.

PMID:40393172 | DOI:10.1016/j.ijheh.2025.114597

Ecotoxicol Environ Saf. 2025 May 19;299:118305. doi: 10.1016/j.ecoenv.2025.118305. Online ahead of print.

ABSTRACT

Phthalates, as a class of known endocrine disruptors, have been controversial because of their potential carcinogenicity and toxicity. Diisononyl cyclohexane-1,2-dicarboxylate (DINCH) is considered to be less toxic and more prone to environmental degradation, and is widely used as a substitute for phthalate. With the increasing use of DINCH in consumer products and industrial materials, the frequency of its detection in the air and human urine has also increased, which has aroused concern about its potential toxicity in food safety. Despite the increasing popularity of DINCH, toxicological studies on this topic are still limited. This study first predicted the hepatotoxicity and carcinogenicity of DINCH via the ADMETlab 3.0 platform. Next, the potential hepatotoxic genes associated with DINCH were collected through multiple databases, and a gene network was constructed. Through proteinprotein interaction, GO enrichment and KEGG pathway analyses, we elucidated the primary mechanism by which DINCH may induce hepatotoxicity. The expression of the selected key genes in related diseases was subsequently validated via the liver cancer database of TCGA and the NASH dataset of GEO. In addition, molecular docking technology and dynamics simulation were used to simulate the interaction and binding ability between DINCH and the core target. Cell experiments verified that DINCH increases hepatotoxicity primarily by upregulating TNF, TP53, and PPARG. In summary, this study elucidates the potential biological mechanisms of DINCH-induced hepatotoxicity, providing new scientific insights for the prevention and management of related toxicities.

PMID:40393321 | DOI:10.1016/j.ecoenv.2025.118305

Ecotoxicol Environ Saf. 2025 May 19;299:118301. doi: 10.1016/j.ecoenv.2025.118301. Online ahead of print.

ABSTRACT

Bisphenol A (BPA), a ubiquitous endocrine-disrupting chemical, is widely used in polymers, plasticizers, and food packaging, raising significant concerns for human health. Growing evidence links BPA exposure to cardiovascular diseases, including diabetic cardiomyopathy (DCM), a severe complication of diabetes characterized by myocardial dysfunction. This study employs an integrative approach combining network toxicology and molecular docking to elucidate the molecular mechanisms underlying BPA-induced DCM. Using computational tools such as ADMETlab2.0, ProTox3.0, GeneCards, OMIM, Swiss Target Prediction, and ChEMBL databases, we systematically predicted BPA's potential to induce DCM and constructed comprehensive disease and BPA target libraries. Venn diagram analysis identified 93 potential targets associated with BPA-induced DCM, and a robust BPA regulatory network was established using Cytoscape. Functional enrichment analyses revealed significant involvement of oxidative stress, insulin signaling, and metabolic pathways in BPA toxicity. Molecular docking simulations demonstrated stable binding interactions between BPA and core targets (INS, AKT1, PPARG, STAT3, PPARA, MMP9), with binding energies ranging from -5.3 to -7.5 kcal/mol. Our findings indicate that BPA may induce DCM through key genes and pathways, including cGMP-PKG signaling pathway, insulin signaling pathway, AMPK signaling pathway, and HIF-1 signaling pathway. This study provides a novel theoretical framework for understanding the molecular pathogenesis of BPA-induced DCM and highlights the potential of network toxicology in identifying toxic pathways for uncharacterized environmental compounds. These insights offer potential targets for preventive and therapeutic strategies against BPA-associated cardiovascular complications.

PMID:40393322 | DOI:10.1016/j.ecoenv.2025.118301

Ecotoxicol Environ Saf. 2025 May 19;299:118328. doi: 10.1016/j.ecoenv.2025.118328. Online ahead of print.

ABSTRACT

4-hydroxy-4'-isopropoxydiphenylsulfone (BPSIP), a common alternative to bisphenol A (BPA), has been detected in breast milk and across placental barriers. However, the long-term impacts of perinatal exposure to BPSIP on adipogenesis and susceptibility to metabolic disorders later in life remain poorly understood. This study explored the effects of early-life BPSIP exposure on obesity and metabolic dysfunction in a diet-induced obesity model. Pregnant ICR mice were administered with BPSIP via oral gavage at doses of 0.02, 0.1, and 0.5 mg/kg body weight/day from gestational day 6 to postnatal day 21. After weaning, male and female offspring from control and high dose groups were fed either a normal diet (ND) or a high-fat diet (HFD) for 6 weeks. Results showed that perinatal BPSIP exposure significantly increased serum cholesterol levels, parametrial white adipose tissue (pWAT) weight, and body weight in female offspring, whereas males exhibited the opposite trend. Gene expression analyses revealed sex-specific alterations in adipogenesis, lipid metabolism, and endocrine function within pWAT, with these effects being more pronounced in HFD-fed BPSIP-exposed offspring. These findings demonstrate that perinatal exposure to BPSIP disrupts lipid metabolism in a sex-dependent manner, underscoring the potential long-term metabolic risks associated with BPSIP exposure during critical developmental periods.

PMID:40393323 | DOI:10.1016/j.ecoenv.2025.118328

Comp Biochem Physiol C Toxicol Pharmacol. 2025 May 18:110228. doi: 10.1016/j.cbpc.2025.110228. Online ahead of print.

ABSTRACT

Aquatic ecosystems face ever increasing threats from pollutants, including those derived from exposure to bisphenol compounds (BPs). Bisphenols are endocrine disruptors with significant neurotoxic effects. This review examines the neurobehavioural impacts of bisphenol A (BPA) and its analogues (e.g. BPS, BPF, BPAF, and others) in zebrafish (Danio rerio), a widely used model organism in environmental and regulatory toxicology. Behavioural endpoints such as locomotor activity, anxiety, shoaling, and cognitive functions can be measured in zebrafish, providing insight into the potential neurotoxicity of chemicals. Bisphenols disrupt neural processes through mechanisms involving oxidative stress, endocrine disruption, neurotransmitter dysfunction, and altered gene expression related to neurodevelopment. Specific behavioural disruptions include impaired locomotor activity, heightened anxiety, altered social behaviours, and visual disturbances, often linked to structural damage in the nervous system. While BPA remains the most studied compound, evidence suggests other BPA analogues may have comparable or greater neurobehavioural toxicity. Implicated mechanisms underlying bisphenol-mediated behavioural events in zebrafish include cortisol metabolism, antioxidant defence, serotoninergic receptor signaling, and glutamate receptor signaling, revealing complex interactions that require further investigation. In addition, emerging studies point to the transgenerational effects of these compounds on neurobehavioural functions, necessitating further exploration of behaviour. This comprehensive review underscores the need for expanded research into the molecular pathways underlying BPs-induced neurotoxicity to help formulate better mitigation strategies and regulatory policies.

PMID:40393573 | DOI:10.1016/j.cbpc.2025.110228

NPJ Sci Food. 2025 May 20;9(1):81. doi: 10.1038/s41538-025-00445-4.

ABSTRACT

In late-stage type 2 diabetes mellitus (T2DM), impaired islet β cell function leads to absolute insulin deficiency, thereby disrupting blood glucose homeostasis. GLP-1, an incretin hormone, stimulates insulin secretion from islet β cells post-meals. This study investigated the effects of anthocyanin cyanidin-3-O-glucoside (C3G) on GLP-1 secretion using STC-1 (intestinal endocrine L cells) and NIT-1 (islet β cells). In a co-culture system, C3G treatment increased GLP-1 secretion in STC-1 cells, promoting insulin release in NIT-1 cells under high glucose. Mechanistically, C3G activated the PPARβ/δ-β-catenin-TCF-4 pathway in STC-1 cells, enhancing PG precursor transcription and GLP-1 synthesis.Inhibiting PPARβ/δ with GSK0660 blocked this C3G-induced upregulation. Overall, C3G stimulates GLP-1 secretion from intestinal L cells via this pathway, indirectly boosting insulin release from β cells. These findings enhance T2DM mechanism understanding and suggest the potential of C3G in GLP-1-based T2DM therapy.

PMID:40393996 | DOI:10.1038/s41538-025-00445-4

Se Pu. 2025 Jun;43(6):640-649. doi: 10.3724/SP.J.1123.2024.04002.

ABSTRACT

Phthalates （PAEs） are widely employed as plasticizers in plastic products that are used in industrial， agricultural， food， medical， and other fields. PAEs are relatively weakly bonded to plastic products through non-covalent interactions. Consequently， PAEs can easily leak from the product into the environment， which exposes the public to PAEs through food intake， skin absorption from personal care products， and by inhaling air. Related studies have shown that PAEs are endocrine-disrupting substances and that long-term exposure to PAEs may result in diseases of the nervous， reproductive， cardiovascular and immune systems. In addition， excessive exposure to PAEs may trigger inflammatory responses and induce tumors. Therefore， establishing a highly sensitive assay for determining PAE levels in the human body following exposure is an important objective. PAEs generally have half-lives of less than 24 h； they are rapidly metabolized through enzymatic hydrolysis after entering the human body and excreted through urine. Therefore， most studies have focused on PAE metabolites as target compounds； hence， human body exposure to PAEs can be assessed by analyzing the types and levels of these metabolites. Herein， we established a method for simultaneously determining ten phthalate （PAE） metabolites in human urine using ultra performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）. The ten PAE metabolites in urine were separated using an ACQUITY UPLC BEH Phenyl column （50 mm×2.1 mm， 1.7 μm）. Gradient elution was performed using 0.1% formic acid aqueous solution and 0.1% formic acid in acetonitrile as the mobile phases， at a flow rate of 0.5 mL/min， a column temperature of 40 ℃， and a sample size of 20 μL. Data were acquired in negative-ion electrospray ionization （ESI） and multiple reaction monitoring （MRM） modes， and quantified using the isotope internal standard method. The method was found to be highly specific， with the ten PAE metabolites exhibiting good linearities in their linear ranges， with limits of detection （LODs） and quantification （LOQs） of 0.03-0.3 and 0.1-1 ng/mL， respectively. Under the four quality control （QC） levels， the intra-day and inter-day precisions of the ten PAE metabolites were all ≤8.3%， and the accuracy ranged from ‒10.5% to 7.3%. The method was used to assess the exposure levels of PAE metabolites in the urine samples of 60 volunteers， with 1‒6 kinds of PAE metabolites detected in the urine of each volunteer. This method is sensitive， accurate， simple， efficient， and suitable for the large-scale biological monitoring of PAE metabolites.

PMID:40394743 | DOI:10.3724/SP.J.1123.2024.04002

Environ Sci Technol. 2025 May 18. doi: 10.1021/acs.est.4c10887. Online ahead of print.

ABSTRACT

Several adverse outcome pathways (AOPs) describe the effects of endocrine disrupting compounds on estrogen signaling. Substantial data support an AOP related to estrogen receptor (ER) antagonism, leading to decreased fecundity in fish. In this study, data were generated for an ER agonism AOP leading to reduced fecundity in avian species (AOP537). Chicken embryos and the chicken leghorn male hepatoma cell line, LMH, were used to elucidate key events associated with estrogen signaling following exposure to 17α-ethinylestradiol (EE2) and bisphenol A (BPA). Embryos were exposed via egg injection. Viability and hepatic estrogen-responsive gene expression data were collected at midincubation (embryonic day [ED] 11). Changes in plasma vitellogenin (VTG), gonad morphology and growth were evaluated prior to pipping (ED20). Both chemicals dysregulated estrogen-responsive genes in hepatic tissue and increased plasma VTG concentrations. In LMH spheroids, EE2 and BPA altered estrogen-responsive genes and VTG concentrations at 24 and 48 h, respectively. Gonadal histology revealed oocyte-type cells and loss of testicular cords in male embryos exposed to EE2 and BPA. Overall, EE2 and BPA upregulated VTG mRNA expression, increased plasma VTG, and caused impairments in gonadal development. These results contribute avian-specific evidence to support an endocrine disruption AOP describing the relationship between disrupted VTG synthesis and impaired reproduction.

PMID:40383999 | DOI:10.1021/acs.est.4c10887

Lipids. 2025 May 19. doi: 10.1002/lipd.12448. Online ahead of print.

ABSTRACT

This study examines the antioxidant activities, fatty acid composition, cytotoxicity predictions, and endocrine-disrupting potential of metabolites from orchid methanolic-flower extracts. In silico analyses, including molecular docking, NCI-RDG, FMO, ELF, LOL, and MEP mapping, were conducted to explore noncovalent interactions, electronic properties, reactivity, and charge distribution of key metabolites, providing insights into their bioactivity and mechanisms of action. Antioxidant activity, evaluated via the DPPH assay, showed an IC₅₀ value of 12.83 mg/mL for the methanolic extract, outperforming the positive control (BHT, IC₅₀ = 18.00 mg/mL). High flavonoid content, expressed as quercetin equivalents, confirmed the presence of bioactive compounds, including quercetin and gallic acid. The fatty acid (FA) profile of Anacamptis papilionacea fixed oil, analyzed by GC-MS, revealed palmitic acid, α-linolenic acid, 8,11,14-eicosatrienoic acid, and docosahexaenoic acid as dominant FAs, constituting 79.47% of the total oil. Molecular docking showed strong binding interactions of these FAs with the human glucocorticoid receptor. Cytotoxicity predictions indicated promising activity against melanoma and lung carcinoma cells, particularly with 8,11,14-eicosatrienoic acid and docosahexaenoic acid. Endocrine-disrupting potential was evaluated through molecular binding with 14 nuclear receptors, showing varying affinities, particularly for estrogen, androgen, and glucocorticoid receptors. These findings highlight the bioactivity and therapeutic potential of A. papilionacea metabolites, emphasizing their antioxidant, cytotoxic, and receptor-binding capabilities. Further experimental studies are warranted for clinical validation.

PMID:40384102 | DOI:10.1002/lipd.12448

PNAS Nexus. 2025 May 12;4(5):pgaf148. doi: 10.1093/pnasnexus/pgaf148. eCollection 2025 May.

ABSTRACT

Endocrine-disrupting chemicals (EDCs), such as 17β-estradiol (E2) and bisphenol A (BPA), can induce DNA damage, leading to genomic instability and cell death. Laccase, an enzyme secreted by diverse organisms, plays a critical role in mitigating the cytotoxicity of these contaminants. Despite its importance, the dynamic evolution and interaction mechanisms of EDCs and DNA in laccase catalysis remain poorly understood. This study investigates the interactions between EDCs and DNA during laccase-induced polymerization transfer at a molecular level. As the DNA concentration was increased from 0 to 7.575 nM, the pseudo-first-order kinetic constants for E2 and BPA decreased by 2.03 and 2.10 times, respectively. DNA-bound EDCs disrupted the catalytic activity and stability of laccase, thereby delaying the polymerization transfer rate of EDCs. E2 and BPA bound to DNA base pairs via groove and intercalative modes, respectively. Laccase-induced polymerization reduced damage to the DNA helix and base stacking caused by EDC binding. Moreover, the resulting DNA-EDC-precipitated polymers, formed through continuous laccase polymerization, exhibited denser and more complex structures compared with spherical EDC-precipitated polymers, confirming DNA encapsulation and/or binding. This work underscores the intramolecular mechanisms of EDC interaction with DNA in vitro during the laccase-induced polymerization, offering efficient ways to mitigate the genotoxicity of EDCs.

PMID:40386681 | PMC:PMC12082286 | DOI:10.1093/pnasnexus/pgaf148

Integr Comp Biol. 2025 May 19:icaf039. doi: 10.1093/icb/icaf039. Online ahead of print.

ABSTRACT

Perchlorate is an endocrine disrupting compound (EDC) used for its oxidative properties and has been detected in many industrialized countries in drinking water, soil, foods, and breast milk. Perchlorate competitively inhibits the uptake of iodide into the thyroid, thus reducing thyroid hormone synthesis. Perchlorate causes steatosis in the liver, alters gonadal development, and increases tubule size in kidneys in some fish models but not others. Much less is known of perchlorate's effects on mammals with respect to these organs. We examined the morphological effects of environmentally relevant concentrations (0ppm, 10ppm, and 100ppm) of sodium perchlorate on the thyroid, liver, kidneys, testes, and ovaries on mice exposed from conception. Sexually mature female mice were randomly divided into the three treatment groups, bred, and exposed to perchlorate via water until offspring were weaned at postnatal day 36 (P36). Offspring continued exposure for 49 days at the same concentration as their mother, euthanized at P85, whole body perfused with 4% paraformaldehyde, and target organs were dissected, sectioned, and stained using hematoxylin and eosin. Perchlorate exposed mice displayed a significant decrease in colloid area and a significant increase in follicle density, angiogenesis, and lipid accumulation within the thyroid. The liver showed a significant increase in the presence of ballooned hepatocytes and lipid accumulation. Within the kidney, we found perchlorate significantly altered nephron tubule thickness. In the testes, perchlorate exposure caused an increase in disorganized seminiferous tubules, an increase in Leydig cell nuclei area. and an increase in the size of blood vessels. There were no effects observed in the ovaries of perchlorate exposed mice compared to the control. These results indicate many commonalities among fishes and other mammalian models but also the need for understanding disparate results between model species.

PMID:40388306 | DOI:10.1093/icb/icaf039

Ecotoxicol Environ Saf. 2025 May 17;298:118343. doi: 10.1016/j.ecoenv.2025.118343. Online ahead of print.

ABSTRACT

Benzophenone-3 (BP3) is a prevalent environmental UV filter widely used in personal care products, and titanium dioxide nanoparticles (nano-TiO₂), another commonly applied material in consumer goods and industrial applications, may coexist with BP3 in environmental media. This study investigates the potential parental transfer of BP3 and transgenerational effects on development and thyroid hormone homeostasis in F1 larvae following lifetime parental exposure to BP3 and nano-TiO₂. Zebrafish embryos were exposed to environmentally relevant concentrations of BP3 (10 μg/L), nano-TiO₂ (100 μg/L), and their combination from 6 hours post-fertilization (hpf) to 150 days. Results showed the presence of BP3 in the gonads of F0 and F1 embryos, with combined exposure alleviating BP3 accumulation. Parental BP3 exposure increased BP3 levels in F1 embryos, causing various developmental neurotoxic effects including decreased survival rates, somite counts, hatching rates, midbrain-hindbrain junction abnormalities, and heightened locomotor responses in F1 offspring. These effects were accompanied by their reduced axonal growth, impaired neurogenesis, and altered neurotransmitters levels. Additionally, decrease thyroxin (T4) levels were observed in F1 eggs, consistent with F0 adults' plasma levels, indicating maternal transmission of thyroid endocrine disruption to the offspring. Furthermore, significant changes in the expression of genes related to hypothalamic-pituitary-thyroid (HPT) axis were observed across two generations, potentially contributing to transgenerational thyroid hormone disruption. Taken together, our study illustrated that parental exposure to BP3 and nano-TiO₂ can induce developmental neurotoxicity and thyroid endocrine disruption in offspring, emphasizing the importance of conducting transgenerational toxicity tests for assessing the environmental risks associated with co-exposure to UV filters and nanoparticles.

PMID:40383070 | DOI:10.1016/j.ecoenv.2025.118343

J Adv Res. 2025 May 16:S2090-1232(25)00352-2. doi: 10.1016/j.jare.2025.05.034. Online ahead of print.

ABSTRACT

BACKGROUND: Parkinson's Disease (PD), a complex neurodegenerative disorder, is increasingly recognized as a systemic condition involving multi-organ interactions. Emerging evidence highlights roles of organ-brain axes (lung-, liver-, heart-, muscle-, bone-, and gut-brain) in PD pathogenesis. These axes communicate via neural, circulatory, endocrine, and inflammatory pathways, collectively driving neurodegeneration. For example, lung dysfunction in PD involves respiratory impairment and inflammatory signaling, while gut dysbiosis triggers α-synuclein aggregation via the vagus nerve. Such cross-organ interactions underscore PD's systemic nature, challenging traditional brain-centric models.

AIM OF REVIEW: 1. Decipher mechanisms linking peripheral organs (e.g., lung, gut) to PD via shared pathways. 2. Explore bidirectional organ-brain interactions (e.g., liver metabolism affecting neurotoxin clearance). 3. Propose multi-organ therapeutic strategies targeting integrated signaling networks. Key Scientific Concepts of Review. 1. Lung-Brain Axis: Respiratory dysfunction (motor impairment, inflammation) exacerbates neurodegeneration. 2. Liver-Brain Axis: Metabolic dysregulation alters neurotoxin clearance; drugs (e.g., levodopa) impact liver function. 3. Heart-Brain Axis: Autonomic dysfunction reduces cerebral blood flow; neuroendocrine changes promote α-synuclein pathology. 4. Muscle-Brain Axis: Neuromuscular/metabolic disruptions worsen motor symptoms. 5. Bone-Brain Axis: Bone-derived hormones (osteocalcin, OCN) and inflammation influence cognition. 6. Gut-Brain Axis: Dysbiosis drives α-synuclein misfolding; gut metabolites modulate neuroinflammation. Integrated Mechanisms: Shared pathways (neuroinflammation, oxidative stress) create a regulatory network, suggesting therapies targeting multi-organ crosstalk (e.g., probiotics, anti-inflammatory agents).

PMID:40383292 | DOI:10.1016/j.jare.2025.05.034

Spectrochim Acta A Mol Biomol Spectrosc. 2025 May 13;341:126403. doi: 10.1016/j.saa.2025.126403. Online ahead of print.

ABSTRACT

Phthalates, classified as priority environmental contaminants, have driven intensive methodological development for environmental monitoring due to their well-documented endocrine-disrupting effects. Despite these imperatives, the design of optical probes for phthalate detection remains challenging probably due to the lack of suitable functional groups/sensing mode. Additionally, the reported probes were applied in the form of suspensions, resulting in difficulties in separation and recovery during the practical applications. Addressing these limitations, we engineered an amphiphilic BODIPY derivative (BOD-Bea) featuring a bespoke molecular architecture that self-assembles into non-fluorescent aggregates in aqueous media. Upon dipentyl phthalate (DPP) binding, significant fluorescence and absorption enhancements were elicited through the mechanism of disaggregation-induced emission (DIE). From the titration experiments, both the fluorescence emission at 653 nm and absorption at 576 nm demonstrate linear correlations with DPP concentrations in the range of 0-26 μM. The calculated LODs were determined to be 0.11 μM for fluorescence detection and 1.24 μM for absorption measurement. Detailed binding mechanism reveals that the probe achieves specific DPP recognition through synergistic interactions: π-π stacking anchoring the benzene ring moiety and hydrophobic capturing of the alkyl chain. Finally, probe BOD-Bea has been successfully employed to quantify DPP in the real water samples with good recoveries. Meanwhile, two instrument-free solid sensors based on BOD-Bea (i.e., test paper and hydrogel) are fabricated to rapidly and sensitively monitor DPP. This strategy overcomes the disadvantages of complex and costly pre-treatment of traditional methods and provides a molecular design basis for rapid on-site detection.

PMID:40381237 | DOI:10.1016/j.saa.2025.126403

Lancet Planet Health. 2025 May;9(5):e364-e373. doi: 10.1016/S2542-5196(25)00080-4.

ABSTRACT

BACKGROUND: Toxicological evidence suggests that ambient air pollution has endocrine-disrupting properties that can affect menstrual cycle functioning, which represents an important marker of women's reproductive health. We aimed to estimate the effect of short-term and long-term PM_2·5 exposure on menstrual cycle outcomes across the USA, Brazil, and Mexico using self-reported data from a mobile health app.

METHODS: For this prospective observational study, we collected de-identified self-reported data from the Clue mobile health app, in which users self-tracked menstruation cycles. For the current study, eligible participants were aged 18-44 years, were not using hormonal birth control, and lived in one of 230 cities in the USA, Mexico, or Brazil. The primary outcome of interest at the city level was the proportion of menstrual cycles with abnormally short length (<24 days) and long length (>38 days) of all cycles recorded. The primary outcome at the cycle level was a binary indicator: abnormal cycle length (<24 days or >38 days) or not (normal cycle length). We used regression analyses to evaluate associations between long-term PM_2·5 concentrations (mean concentration between 2016 and 2020) and the city-level outcomes after controlling for potential confounders. Conditional logistic regression models were used to evaluate associations between cycle-specific PM_2·5 and if a cycle was of abnormal length within an individual in the dataset, after controlling for time-varying factors.

FINDINGS: Between Jan 1, 2016 and Dec 31, 2020, 92 550 app users residing in 230 cities across the USA, Brazil, and Mexico provided data corresponding to 2 220 281 menstrual cycles, and were included in our main cohort. A significant association was observed between long-term PM_2·5 exposure and the proportion of menstrual cycles of abnormally long or short duration (odds ratio [OR] 1·023 [95% CI 1·013-1·033]) and the proportion of cycles that were specifically abnormally long (OR 1·036 [1·023-1·049]) for every 10 μg/m³ increase in PM_2·5. No associations were identified between short-term PM_2·5 concentrations and abnormal cycle length.

INTERPRETATION: These findings suggest that PM_2·5 exposure affects menstrual cycle outcomes. More research is needed to better elucidate the biological mechanisms through which PM_2·5 affects the menstrual cycle.

FUNDING: None.

PMID:40381631 | DOI:10.1016/S2542-5196(25)00080-4

Environ Pollut. 2025 May 15;377:126467. doi: 10.1016/j.envpol.2025.126467. Online ahead of print.

ABSTRACT

Agricultural plastic films, while boosting crop productivity, may pose significant environmental risks due to additive release during crack degradation. Phthalic acid esters (PAEs) and organophosphate esters (OPEs), widely used as plasticizers and flame retardants respectively, represent two additive categories of the greatest environmental concern due to their persistence and endocrine-disrupting properties. This study systematically investigated the dynamic release of PAEs and OPEs from polyethylene (PE) and biodegradable poly (butylene adipate-co-terephthalate)/polylactic acid (PBAT/PLA)-based films under four simulated agricultural conditions: Natural conditions (NC), UV irradiation (UV), high temperature (HT), and flooding (FC). Uncultivated soil exhibited Σ₈PAEs and Σ₇OPEs approximately of 1317.5 ng/g and 1931.1 ng/g, respectively. During a 360 d incubation period, the contents of PAEs in soil surged during a short-term period, which may link to the desorption of adsorbed contaminant. Biodegradable films released higher PAEs concentrations than PE films, with secondary contamination peaks emerging 180-360 d post-incubation. Scanning electron microscopy (SEM) observations revealed that structural degradation (e.g., cracks/holes) during early degradation (0-180 d) unexpectedly amplified additive leaching in later stages, contrasting with assumptions of reduced contamination risks over time. UV irradiation had a photo-degradation effect on PAEs further accelerated the release of pollutants by 25-40 %, while high temperature and flooding conditions showed limited promoting effects along with NC conditions. These findings highlight the need for additive-free formulations and environment-specific mulch management policies to mitigate soil contamination risks.

PMID:40381682 | DOI:10.1016/j.envpol.2025.126467

Reprod Toxicol. 2025 May 15:108945. doi: 10.1016/j.reprotox.2025.108945. Online ahead of print.

ABSTRACT

Cryptorchidism, a condition associated with male infertility, is exacerbated by exposure to environmental endocrine disruptors such as flutamide. This study investigates the molecular mechanisms of cryptorchidism and potential interventions targeting endocrine disruptor-induced testicular damage. A rat model of congenital cryptorchidism was established via prenatal flutamide exposure, and testes were harvested at postnatal day 90. Testicular histology, transcriptome sequencing, bioinformatic analysis, sperm analysis, immunohistochemistry, and lentiviral vector transfection were conducted. Cryptorchid testes exhibited impaired seminiferous tubule development, significant reductions in sperm count, and increased sperm abnormalities. Tight and gap junction proteins essential for blood-testis barrier (BTB) integrity, including Claudin-11, Occludin, and Connexin-43, were markedly downregulated. Transcriptomic analysis revealed activation of the p38 MAPK signaling pathway and excessive apoptosis in cryptorchid testes. Overexpression of Connexin-43 restored BTB integrity and suppressed the p38 MAPK pathway, rescuing spermatogenesis. These findings underscore the role of environmental anti-androgens in cryptorchidism pathogenesis and highlight Connexin-43 as a potential therapeutic target for mitigating testicular damage caused by endocrine disruptors.

PMID:40381864 | DOI:10.1016/j.reprotox.2025.108945

EXCLI J. 2025 Mar 27;24:479-507. doi: 10.17179/excli2024-7822. eCollection 2025.

ABSTRACT

Ethylbenzene (EB) was placed on List 2 for Tier 1 endocrine screening in the U.S. EPA's two-tiered Endocrine Disruptor Screening Program (EDSP) and was scheduled for evaluation under TSCA. Results of toxicology studies on EB were used to evaluate estrogen, androgen, thyroid, and steroidogenic (EATS) endpoints by a Weight of Evidence (WoE) methodology, as required by U.S. EPA and OECD guidelines for evaluating a chemical's endocrine disruptive potential. The WoE method involved problem formulation, systematic literature search and selection, data quality evaluation, relevance weighting of endpoint data, and application of specific interpretive criteria. Data on EB were sufficient to assess its effects on endpoints that would be expected to respond to chemicals that operate via EATS modes of action (MoAs) in various screening assays (Tier 1) and toxicity tests (Tier 2) that evaluate reproduction, development, and sub-chronic and chronic toxicity. In those studies, EB produced a pattern of responses inconsistent with the responses that would be expected for hormones and chemicals known to operate via EATS MoAs. Endocrine-sensitive endpoints that respond to EB administration generally do so only at dose levels above its kinetic maximum dose, indicating a lack of relevance to potential effects at lower dose levels in either the test species or humans. This comprehensive WoE evaluation demonstrates that EB lacks the potential to exhibit endocrine disruptive properties and cannot be deemed an endocrine disruptor or potential endocrine disruptor. Because this WoE evaluation was based largely on Tier 2-level studies of the type considered by the U.S. EPA and OECD to be more definitive than results of Tier 1 EDSP screening results, no additional useful information would be obtained by subjecting EB to further endocrine screening. As such, further endocrine screening of EB would be unjustified from animal welfare perspectives. This analysis supports a regulatory decision to halt further testing of EB for endocrine disruption unless unique and compelling data to the contrary arise. See also the graphical abstract(Fig. 1).

PMID:40376433 | PMC:PMC12078780 | DOI:10.17179/excli2024-7822

Cancer Epidemiol Biomarkers Prev. 2025 May 16. doi: 10.1158/1055-9965.EPI-24-1694. Online ahead of print.

ABSTRACT

BACKGROUND: Endocrine-disrupting chemicals (EDCs) found in many household and personal care products have hormonal properties and effects on the mammary gland. It is unclear whether urinary concentrations of EDCs are associated with higher percent breast density, a major risk factor of breast cancer.

METHODS: We conducted a cross-sectional study of 97 college-aged women. We quantified individual levels of bisphenol A, bisphenol S, bisphenol F, triclosan, triclocarban, 3-benzophenone, seven phthalate metabolites, four parabens, and two other phenols in three 24-hour urine samples combined into a single pooled sample. Each woman had non-enhanced magnetic resonance imaging (MRI) to assess percent breast density. Associations between estimated concentrations of individual EDCs and percent breast density were analyzed using adjusted linear regression.

RESULTS: There was no evidence of statistically significant increases in mean percent breast density in the middle or highest tertile for any EDC measured. There was a suggestion that the mean percent breast density was elevated in individuals in the middle and highest tertile level of ethyl-paraben compared to those in the lowest tertile, with a relative increase in mean percent breast density of 16% (β ̂=1.16, 95%CI: 0.92-1.46) in tertile 2 and 24% (β ̂=1.24, 95%CI: 0.99-1.57) in tertile 3, relative to tertile 1 (ptrend=0.07). Similar trends in percent breast density were observed for methyl-, propyl-, and butyl-paraben.

CONCLUSIONS: Urinary levels of EDCs were not associated with percent breast density in college-aged women.

IMPACT: The estimated effect of EDCs on the breast tissue of young women is unclear and warrants larger studies.

PMID:40377690 | DOI:10.1158/1055-9965.EPI-24-1694

Biochem Biophys Res Commun. 2025 May 8;770:151978. doi: 10.1016/j.bbrc.2025.151978. Online ahead of print.

ABSTRACT

The increased prevalence of sleep disturbances in modern society is frequently linked to various metabolic disorders, including insulin resistance, obesity, hypertension, fatty liver disease, and cardiometabolic complications. Melatonin, a pineal gland-secreted neurohormone, plays a pivotal role in maintaining the circadian rhythm. It is involved in regulating adipose tissue development, lipid accumulation, browning of white adipose tissue, and activation of brown adipose tissue. The adipose tissue is a dynamic endocrine organ that secretes hormones and cytokines. Recent research has highlighted the significant role of melatonin in the modulation of lipid metabolism, adipogenesis, and thermogenesis in adipose tissues. Circadian rhythms are important in synchronizing metabolic functions with environmental cues, such as light and dark, feeding-fasting states, etc. Irregular sleep patterns, shift work, and exposure to artificial light at night disrupt these rhythms, affecting circadian regulation and compromising metabolic health. Melatonin imbalance due to sleep disturbances results in metabolic dysfunction, increased fat storage, and adipose tissue inflammation. As circadian rhythm and melatonin are both related, a change in circadian rhythm affects the physiology of adipose tissues thereby precipitating metabolic complications through melatonin signaling. This study attempted to understand the mechanisms by which melatonin influences adipose tissue activity, highlighting the role of circadian rhythms in this process. This will enable the development of melatonin-based therapies to mitigate the adverse effects of chronobiological disturbances on the physiology of adipose tissue. Understanding these interactions will provide novel insights for combating obesity and related metabolic conditions.

PMID:40378618 | DOI:10.1016/j.bbrc.2025.151978

Reprod Toxicol. 2025 May 14;135:108949. doi: 10.1016/j.reprotox.2025.108949. Online ahead of print.

ABSTRACT

Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder among women of reproductive age, frequently causing infertility. This study investigates the influence of endocrine-disrupting chemicals (EDCs) on ovarian reserve parameters in women with PCOS-related infertility. A cohort of 61 women with PCOS, aged 29.90 ± 3.64 years, was recruited from Dr. Nagori's Institute for Infertility in Ahmedabad, Gujarat. Serum levels of Bisphenol A (BPA), Mono-ethylhexyl phthalate (MEHP), and Di-ethylhexyl phthalate (DEHP) were measured using high-performance liquid chromatography (HPLC). Ovarian reserve markers were assessed, including antral follicle count (AFC) and anti-Müllerian hormone (AMH) levels. Hormonal profiles and metabolic parameters were also analyzed. Correlations between EDCs and ovarian reserve markers were evaluated using Pearson correlation and regression analyses. The study found serum mean levels of BPA (77.80 ± 51.82 ng/ml), MEHP (37.43 ± 19.85 μg/ml), and DEHP (5.77 ± 7.21 μg/ml). Participants exhibited typical PCOS hormonal profiles with elevated testosterone and AMH levels, and significant insulin resistance was observed. Correlation analysis showed a positive relationship between AMH levels and AFC (r = 0.47, p = 0.01). However, no significant associations were found between EDC exposure and ovarian reserve markers. A high prevalence of adenomyosis and bilateral polycystic ovaries was noted among the participants. While metabolic and hormonal disruptions are prominent in PCOS, the direct impact of EDCs on ovarian reserve parameters appears minimal. This study highlights the necessity of addressing metabolic health and environmental exposures in managing PCOS related infertility to improve reproductive outcomes.

PMID:40379154 | DOI:10.1016/j.reprotox.2025.108949

Nat Rev Urol. 2025 May 16. doi: 10.1038/s41585-025-01031-9. Online ahead of print.

ABSTRACT

Endocrine-disrupting chemicals (EDCs) are natural or synthetic compounds that are ubiquitous in the environment and in daily-usage products and interfere with the normal function of the endocrine system leading to adverse health effects in humans. Exposure to these chemicals might elevate the risk of metabolic disorders, developmental and reproductive defects, and endocrine-related cancers. Prostate cancer is the most common hormone-dependent cancer in men, and the fifth leading cause of cancer-related mortality, partly owing to a lack of knowledge about the mechanisms that lead to aggressive castration-resistant forms. In addition to the dependence of early-stage prostate cancer on androgen actions, the prostate is a target of oestrogenic regulation. This hormone dependence, along with the fact that exogenous influences are major risk factors for prostate cancer, make the prostate a likely target of harmful actions from EDCs. Various sources of EDCs and their different modes of action might explain their role in prostate carcinogenesis.

PMID:40379948 | DOI:10.1038/s41585-025-01031-9

Arch Toxicol. 2025 May 15. doi: 10.1007/s00204-025-04083-3. Online ahead of print.

ABSTRACT

Di(2-ethylhexyl)phthalate (DEHP) is widely used as a plasticizer and is associated with potential adverse health effects, including endocrine disruption and organ toxicity. Accurate assessment of DEHP exposure risks requires robust pharmacokinetic models capable of capturing inter-individual variability and integrating human biomonitoring data. This study aimed to develop and validate a population pharmacokinetic model for DEHP and its major metabolites, mono(2-ethylhexyl)phthalate (MEHP), 2-ethyl-5-hydroxy-hexylphthalate (5-OH MEHP), and 2-ethyl-5-oxo-hexylphthalate (5-Oxo MEHP), to quantitatively assess DEHP exposure risks in human populations. Clinical data from DEHP-d₄, a radiolabeled DEHP isotope, were used to construct a pharmacokinetic model using non-linear mixed effects modeling. The model incorporated plasma concentration and urinary excretion data for DEHP and its metabolites. Biomonitoring data were integrated using reverse dosimetry to estimate external exposure levels, and margins of safety were then calculated by comparing these estimates with established reference doses. The model demonstrated robust correlations (R² > 0.99) between external DEHP exposure and internal biomarker levels. Predicted external exposure levels ranged from 0.52 to 157.52 µg/kg/day, with margins of safety varying between 0.13 and 38.17. Despite substantial inter-individual variability, the model accurately captured population-level pharmacokinetic diversity and provided reliable risk assessments. The developed pharmacokinetic model offers a versatile tool for integrating biomonitoring data and conducting rapid, population-specific DEHP risk assessments. These findings underscore the importance of ongoing monitoring and stringent regulatory measures to mitigate DEHP-associated health risks.

PMID:40372421 | DOI:10.1007/s00204-025-04083-3

Environ Sci Technol. 2025 May 15. doi: 10.1021/acs.est.5c01550. Online ahead of print.

ABSTRACT

Perfluorooctanesulfonate (PFOS) is a persistent environmental endocrine disruptor that poses severe threats to mammalian reproductive health upon accumulation in organisms. Therefore, elucidating the mechanisms of PFOS-induced damage and identifying effective protective strategies are of critical importance. In this study, an untargeted metabolomic analysis revealed that PFOS exposure significantly disrupted metabolic homeostasis in oocytes. Using public databases to predict potential target proteins of PFOS and performing KEGG pathway enrichment analysis, we identified the tryptophan metabolism pathway as a key target of PFOS. Molecular docking and molecular dynamics simulations demonstrated specific binding between PFOS and proteins involved in the tryptophan metabolism pathway, leading to dynamic structural alterations in these proteins. Furthermore, supplementation with tryptophan was shown to significantly enhance mitochondrial function in oocytes, regulate the glutathione (GSH)/oxidized glutathione (GSSG) ratio, reduce reactive oxygen species (ROS) levels, and alleviate oxidative stress, thereby mitigating the decline in oocyte quality caused by PFOS exposure. These findings provide novel theoretical insights and research directions for using tryptophan as a protective agent against PFOS-induced reproductive toxicity.

PMID:40372800 | DOI:10.1021/acs.est.5c01550

Toxicol Sci. 2025 May 15:kfaf069. doi: 10.1093/toxsci/kfaf069. Online ahead of print.

ABSTRACT

Zebrafish (Danio rerio) are a popular vertebrate model for high-throughput toxicity testing, serving as a model for embryonic development and disease etiology. However, standardized protocols using zebrafish tend to explore pathologies and behaviors at the organism level, rather than at the organ-specific level. This study investigates the effects of chemical exposures on pancreatic function in whole-embryo zebrafish by integrating network analysis and machine learning, leveraging widely-available datasets to probe an organ-specific effect. We compiled transcriptomics data for zebrafish exposed to 53 exposures from 25 unique chemicals, including halogenated organic compounds, pesticides/herbicides, endocrine-disrupting chemicals, pharmaceuticals, parabens, and solvents. All raw sequencing data were processed through a uniform bioinformatics pipeline for re-analysis and quality control, identifying differentially expressed genes and altered pathways related to pancreatic function and development. Clustering analysis revealed five distinct clusters of chemical exposures with similar impacts on pancreatic pathways with gene co-expression network analysis identifying key driver genes within these clusters, providing insights into potential biomarkers of chemical-induced pancreatic toxicity. Machine learning was utilized to identify chemical properties that influence pancreatic pathway response, including average mass, biodegradation half-life. The random forest model achieved robust performance (4-fold cross-validation accuracy: 74%) over eXtreme Gradient Boosting, support vector machine, and multiclass logistic regression. This integrative approach enhances our understanding of the relationships between chemical properties and biological responses in a target organ, supporting the use of zebrafish whole-embryos as a high-throughput vertebrate model. This computational workflow can be leveraged to investigate the complex effects of other exposures on organ-specific development.

PMID:40373795 | DOI:10.1093/toxsci/kfaf069

Chem Res Toxicol. 2025 May 15. doi: 10.1021/acs.chemrestox.5c00018. Online ahead of print.

ABSTRACT

Transthyretin (TTR) is a key transporter of the thyroid hormone thyroxine, and chemicals that bind to TTR, displacing the hormone, can disrupt the endocrine system, even at low concentrations. This study evaluates computational modeling strategies developed during the Tox24 Challenge, using a data set of 1512 compounds tested for TTR binding affinity. Individual models from nine top-performing teams were analyzed for performance and uncertainty using regression metrics and applicability domains (AD). Consensus models were developed by averaging predictions across these models, with and without consideration of their ADs. While applying AD constraints in individual models generally improved external prediction accuracy (at the expense of reduced chemical space coverage), it had limited additional benefit for consensus models. Results showed that consensus models outperformed individual models, achieving a root-mean-square error (RMSE) of 19.8% on the test set, compared to an average RMSE of 20.9% for the nine individual models. Outliers consistently identified in several of these models indicate potential experimental artifacts and/or activity cliffs, requiring further investigation. Substructure importance analysis revealed that models prioritized different chemical features, and consensus averaging harmonized these divergent perspectives. These findings highlight the value of consensus modeling in improving predictive performance and addressing model limitations. Future work should focus on expanding chemical space coverage and refining experimental data sets to support public health protection.

PMID:40371923 | DOI:10.1021/acs.chemrestox.5c00018

Aquat Toxicol. 2025 Jul;284:107398. doi: 10.1016/j.aquatox.2025.107398. Epub 2025 May 4.

ABSTRACT

Tebuconazole (TBZ) is a triazole fungicide broadly used to control fungal diseases in agricultural crops, fruit-bearing plants and forestry plantations. However, its increasing use and release into aquatic environments has raised concerns about its hazardous effects on the health of fish. Thus, the aim of the present study was to review the scientific literature on the ecotoxicological effects of TBZ and TBZ-based commercial formulations on fish. Historical review data (publication year and geographical distribution), TBZ type, experimental design, fish species, habitat, life stage, tissue/organ, lethal concentration (LC₅₀), concentration and exposure time, biomarkers and effects were compiled and critically analyzed. Studies were mainly conducted with freshwater species at adult and larval stages, whereas no data were find for marine fish species. Zebrafish, (Danio rerio) was the most assessed species. Both TBZ and TBZ-based commercial formulations induced oxidative stress, endocrine disruption, neurotoxicity, genotoxicity, histopathologies, behavior impairments and mortality on fish. TBZ can induce synergistic and antagonistic effects on fish when it is combined to other pesticides. Overall, the current study has shown the potential hazardous effects of TBZ and TBZ-based commercial formulations on the health of fish.

PMID:40367844 | DOI:10.1016/j.aquatox.2025.107398

Int J Mol Sci. 2025 Apr 26;26(9):4120. doi: 10.3390/ijms26094120.

ABSTRACT

Inflammation of the exocrine pancreas accompanies autoimmune diabetes in mouse models and humans. However, the relationship between inflammation in the exocrine and endocrine (islet) compartments has not been explored. To address this issue, we used a transgenic mouse model in which autoimmune diabetes is acutely induced after the transfer of islet beta cell-specific transgenic T cells. Histological analyses demonstrated that inflammation of the exocrine pancreas, which was initially mild, resulted in the transient but widespread disruption of acinar tissue. Islet inflammation preceded exacerbated exocrine pathology, progressed to T cell-induced islet damage/destruction and persisted when exocrine inflammation subsided. Heparanase-1 (HPSE-1), an endoglycosidase that degrades heparan sulfate in basement membranes (BMs), when preferentially expressed in recipient cells but not donor (HPSE-1-deficient (HPSE-KO)) T cells, played a critical role in both exocrine and islet inflammation. In this context, HPSE-1 facilitates the passage of autoimmune T cells across the sub-endothelial basement membrane (BM) of pancreatic blood vessels and initially into the exocrine tissue. Peak exocrine inflammation that preceded or accompanied the acute onset of diabetes and HPSE-1 potentially contributed to acinar damage. In contrast to inflammation, HPSE-1 expressed by donor T cells played a key role in the induction of diabetes by allowing autoimmune T cells to traverse peri-islet BMs in order to destroy insulin-producing beta cells. Overall, our findings suggest that major exocrine pancreas injury is not required for the initiation of autoimmune islet damage and is not essential at the time of diabetes onset.

PMID:40362360 | PMC:PMC12071485 | DOI:10.3390/ijms26094120

Int J Mol Sci. 2025 Apr 25;26(9):4081. doi: 10.3390/ijms26094081.

ABSTRACT

Bisphenol A (BPA) is a common synthetic chemical compound classified as an endocrine disruptor. It affects multiple physiological systems in the body, including the female reproductive system, particularly granulosa cells (GCs) in the ovaries, where steroidogenesis occurs. This study investigated the impact of various BPA concentrations (environmentally relevant concentrations of 0.001 µM and 0.1 µM and toxicological concentration of 100 µM) and exposure times (24 and 72 h) on cell viability and counts and in vitro production of estradiol and progesterone in human GCs collected from waste follicular fluid of IVF patients. Gene expression analysis of 182 genes associated with steroidogenesis and apoptosis was performed in GCs using PCR arrays, followed by protein expression analysis by Western blot. Our results demonstrate that after longer BPA exposure (72 h), a higher concentration of BPA (100 µM) negatively affects the cellular viability and counts and significantly alters steroid hormone biosynthesis in vitro, leading to reduced concentrations of estradiol and progesterone in the culture medium. We found that all BPA concentrations altered the expression of different steroidogenesis- and apoptosis-related genes in GCs. At 0.001 μM, BPA exposure decreased the expression of TRIM25, UGT2B15, CASP3, and RPS6KA3 genes and increased the expression of NR6A1 and PPID genes. At 0.1 μM, BPA increased the expression of AR, HSD3B1, BID, IKBKG, and PPID genes while reducing the expression of TRIM25 and CASP3 genes. At the highest concentration of 100 μM, BPA upregulated the expression of AR, GPER30, BID, IKBKG, and PPID genes and downregulated the expression of FOXO1 and UGT2B15 genes. These results highlight BPA's concentration-specific effects on steroidogenesis and apoptosis and show its potential to compromise GC function, with possible negative implications for female fertility and ovarian health, even at environmentally relevant concentrations.

PMID:40362320 | PMC:PMC12071243 | DOI:10.3390/ijms26094081

Nutrients. 2025 Apr 29;17(9):1493. doi: 10.3390/nu17091493.

ABSTRACT

Stunting is a major global health concern, particularly in low- and middle-income countries, due to its persistently high prevalence. It often originates from chronic malnutrition during the critical first 1000 days of life. Maternal and child nutrition are critical determinants of a child's growth and development. This article aimed to explore the impact, causes, and evidence-based strategies to accelerate the reduction of stunting incidence worldwide. This review was undertaken with sources from PubMed, Scopus, Google Scholar, Science Direct, and MEDLINE from October 2024 to January 2025. This review was undertaken with sources from PubMed, Scopus, Google Scholar, Science Direct, and MEDLINE from October 2024 to January 2025 using the keyword "Stunting", "Causes of stunting", "Stunting Impact", "Stunting Intervention", and "Stunting Prevention". The findings highlight the multifactorial causes of stunting, including maternal malnutrition, inadequate breastfeeding and complementary feeding, poor sanitation, and socioeconomic factors. Stunting is associated with impaired linear growth, cognitive deficits, gut dysbiosis, endocrine disruption, anemia, and increased risk of chronic diseases later in life. Addressing stunting demands multisectoral strategies focusing on maternal and child nutrition, infection prevention, improved WASH (Water, Sanitation, and Hygiene) practices, and socioeconomic support. The evidence presented may guide policy development and targeted interventions to prevent stunting and its long-term effects.

PMID:40362802 | PMC:PMC12073730 | DOI:10.3390/nu17091493

Int J Mol Sci. 2025 Apr 29;26(9):4226. doi: 10.3390/ijms26094226.

ABSTRACT

Gestational diabetes mellitus (GDM) requires lifestyle changes that may alter exposure to endocrine-disrupting chemicals (EDCs). This study aimed to assess maternal and fetal exposure to EDCs-including bisphenol-A (BPA), monoethyl phthalate (MEP), and perfluorooctanoic acid (PFOA)-during the COVID-19 pandemic and to evaluate their association with fetal birthweight. Maternal urine (second and third trimester) and paired cord blood samples were analyzed from 58 GDM and 118 non-GDM pregnancies using UPLC-MS/MS. Significant correlations were found between maternal urine and cord blood levels of BPA and MEP. Cord blood BPA levels were significantly lower in GDM mothers (0.35 vs. 0.72 μg/L, p < 0.05), suggesting reduced exposure due to dietary interventions. However, maternal urinary BPA levels in GDM pregnancies were positively associated with fetal birthweight (β = 2.69, p < 0.05), indicating increased susceptibility to obesogenic effects. PFOA was present in all cord blood but only 41% of maternal urine samples. These findings underscore the dual impact of GDM-related lifestyle changes: reduced EDC transfer to the fetus, yet persistent metabolic vulnerability.

PMID:40362466 | PMC:PMC12071538 | DOI:10.3390/ijms26094226

Materials (Basel). 2025 May 7;18(9):2155. doi: 10.3390/ma18092155.

ABSTRACT

Phthalates are compounds widely used as very effective plasticizers of PVC. Unfortunately, they are also widely known to be endocrine disruptors and are detrimental to human health and the environment. For this reason, environmentally friendly plasticizers are being intensively sought after in response to the market needs in the context of sustainable development and legislative changes regarding the use of phthalates. Our research presents an innovative approach to addressing this problem. In this paper, we propose new biobased oligoesters as non-toxic and harmless plasticizers of poly(vinyl chloride). New plasticizers were obtained by polyesterification of saturated dimerized fatty acid (DFA), adipic acid (ADA), triethylene glycol (TEG), and 2-ethylhexanol (2-EH), and were characterized by nuclear magnetic resonance, size exclusion chromatography, and viscosity analyses. The compatibility of the obtained oligoesters with PVC was determined using the method for obtaining PVC films by casting from a THF solution. Selected plasticizers were used to obtain PVC blends at 50 phr. They were then tested for plasticizer migration, hardness, thermogravimetric analysis, differential scanning calorimetry, and mechanical strength. Their properties were compared with the commercially available monomeric plasticizers di(2-ethylhexyl) terephthalate and di(2-ethylhexyl) adipate. The conducted study shows that the oligoesters obtained at a molar ratio of ADA to DFA of 9:1 and using an excess of 2-EH exhibit very good compatibility and plasticizing ability. The use of higher amounts of DFA worsens the compatibility of the oligoesters with PVC. However, a 4:1 ADA-to-DFA molar ratio produced results that still allow for the use of these compounds as plasticizers at lower concentrations or in combination with other plasticizers.

PMID:40363658 | PMC:PMC12072859 | DOI:10.3390/ma18092155

Nutrients. 2025 May 6;17(9):1593. doi: 10.3390/nu17091593.

ABSTRACT

BACKGROUND: Childhood obesity has become a major public health concern worldwide, and increasing attention is being paid to the potential role of endocrine-disrupting chemicals such as parabens. Understanding environmental contributors is essential for early prevention strategies.

OBJECTIVES: The aim of the present research was to determine the presence of parabens in hair samples and to examine its association with excess weight and obesity in a sample of Spanish schoolchildren.

METHODS: A total of 104 cases and 166 controls (3-12 year olds) were recruited. Sociodemographic and lifestyle data and hair and urine samples were gathered. UHPLC-MS/MS coupled to a triple quadrupole detector was used for the quantitative determination of six parabens (methylparaben [MetPB], ethylparaben [EthPB], butylparaben [ButPB], propylparaben [PropPB], and isopropylparaben [i-PropPB]). The relationship between the concentration of parabens in hair and urine was examined according to Spearman correlation coefficients. Finally, binary logistic regression models were constructed to evaluate the relationship of parabens with excess weight/obesity.

RESULTS: Detected paraben levels were higher in cases. A weak correlation was produced between hair and urine concentrations, with the exception of i-PropP (hair)/PropPB (urine) and i-PropP (hair)/i-PropPB (urine) in boys, and i-PropPB (hair)/PropPB (urine) in girls. A high level of PropPB was associated with a 4.67 times greater risk of excess weight/obesity only in the boys.

CONCLUSIONS: In males, a high concentration of PropPB in hair is associated with excess weight and obesity.

PMID:40362902 | PMC:PMC12073634 | DOI:10.3390/nu17091593

Mater Horiz. 2025 May 14. doi: 10.1039/d5mh00627a. Online ahead of print.

ABSTRACT

To cope with the environmental risks posed by pharmaceutical waste, adsorption is considered a viable option due to its simplicity, cost-effectiveness, and reliability. This review explores the opportunities and challenges involved in applying nanomaterial-based adsorbents in their metallic, non-metallic, and hybrid forms for removal of common pharmaceuticals (e.g., antibiotics, beta-blockers, analgesics, non-steroidal anti-inflammatory drugs, endocrine disrupters, and anticancer drugs) from water. To improve the selectivity and scalability of diverse adsorbents against such targets, the adsorption capacity and partition coefficient (PC) of each adsorbent are evaluated. Among the reported materials, magnetic nitrogen-doped carbon displays the highest adsorption capacity (1563.7 mg g^-1) for common targets such as ciprofloxacin, while carbon nanotube-SiO₂-Al₂O₃ has the highest PC (1425 mg g^-1 μM^-1) for estradiol. Despite the advances in adsorption technologies, their commercial applications are yet limited by several defects such as low efficiency, high costs, and poor scalability. This review examines current strategies for addressing pharmaceutical contamination and outlines potential directions for future research.

PMID:40365702 | DOI:10.1039/d5mh00627a

Int J Yoga. 2025 Jan-Apr;18(1):45-57. doi: 10.4103/ijoy.ijoy_212_24. Epub 2025 Apr 22.

ABSTRACT

BACKGROUND: Hormonal imbalance, mitochondrial dysfunctions, and oxidative stress (OS) have been implicated in the pathogenesis of polycystic ovarian syndrome (PCOS) and its associated clinical features. A sedentary lifestyle, exposure to air pollutants, prenatal exposure to endocrine-disrupting chemicals, processed and nutritionally depleted food, rich in trans fats, salts, and sugars, and high BMI specifically in visceral adiposity induce OS. OS damages the mitochondrial DNA, lipids, and proteins that impair mitochondrial function. Sequentially, dysfunctional mitochondria produce more reactive oxygen species that aggravate the OS. Mitochondria is pivotal for ovarian cell functioning for instance steroidogenesis, ovarian follicle development, and energy metabolism. Dysfunctional mitochondria can alter the ovarian follicle functioning leading to ovulatory dysfunction and infertility in PCOS.

AIMS AND OBJECTIVES: This study is designed to investigate the effect of 12-week yoga practice on endocrine parameters, OS, and mitochondrial health, comparing outcomes in yoga and non-yoga groups.

MATERIAL AND METHODS: A total of 75 participants, 32 PCOS females who completed yoga intervention in the yoga group and 29 in the nonyoga group. Hormonal levels were assessed through an immunoassay, while mitochondrial health markers, such as mtDNA copy number (mtDNA CN), reactive oxygen species, and lipid peroxidation were measured through quantitative polymerase chain reaction (qPCR), chemiluminescence, and ELISA respectively. Gene expression related to mitochondrial integrity, respiratory chain, and inflammation was analyzed via reverse transcription qPCR. Additionally, depression severity was also assessed using beck depression inventory II.

RESULT: The Yoga group showed a significant increase in mtDNA-CN and upregulation of transcripts responsible for maintaining mitochondrial integrity and the mitochondrial respiratory chain. In addition, the post-yoga group shows a reduction in, lipid peroxidation, inflammatory, OS markers, and an improvement in telomere length.

CONCLUSION: Yoga positively affects hormonal balance, mitochondrial health, OS, and inflammation in women with PCOS. It also alleviates depression symptoms, highlighting yoga as an effective adjunct therapy for managing PCOS. Regular yoga practice could prevent, delay, and help in managing PCOS symptoms.

PMID:40365366 | PMC:PMC12068466 | DOI:10.4103/ijoy.ijoy_212_24

Vet Med Sci. 2025 May;11(3):e70393. doi: 10.1002/vms3.70393.

ABSTRACT

BACKGROUND: Polystyrene microplastics (PS-MPs) are pervasive pollutants impacting animals across ecosystems, including livestock and wildlife, through contaminated food, water, and air. MPs may disrupt endocrine function, particularly affecting the thyroid gland, which is essential for metabolism and development.

OBJECTIVES: This study investigates the effects of PS-MPs on thyroid function in mice, offering insights relevant to veterinary care by examining changes in gene expression and biochemical markers.

METHODS: PS-MPs of 5 µm diameter were prepared in distilled water after probe sonication. Sixty male Swiss albino mice were divided into three groups: a control group and two treatment groups receiving 0.1 mg and 0.2 mg PS-MPs via oral gavage for 28 days. Mice were anesthetised, and thyroid tissues were collected for histopathological, biochemical, and gene expression analyses. Biochemical tests included catalase, superoxide dismutase, reactive oxygen species, and hormone levels. Histopathology and gene expression (TSHR and TPO) of thyroid-related genes were examined to assess PS-MPs induced effects.

RESULTS: Exposure to PS-MPs in mice led to significant increases in calcium, thyroxin, free T3, free T4, ALP, AST, ALT, and amylase levels, alongside elevated oxidative stress markers. Conversely, the levels of TSH, calcitonin, magnesium and phosphate decreased. Histopathological analysis showed abnormal thyroid follicle development, decrease parafollicular cells, with colloid loss, haemorrhage, and necrosis. Gene expression analysis revealed a marked reduction in TSHR and TPO levels in PS-MPs treated groups, indicating thyroid dysfunction. These findings highlight the profound impact of PS-MPs on thyroid gland function in mice.

CONCLUSION: These findings underscore the potential risks that PS-MPs pose to thyroid health, with potential consequences for other veterinary species. As environmental contamination rises, veterinarians may encounter more endocrine disorders linked to PS-MPs, emphasising the need for further research and preventive measures.

PMID:40367361 | PMC:PMC12077756 | DOI:10.1002/vms3.70393

Vet Med Sci. 2025 May;11(3):e70393. doi: 10.1002/vms3.70393.

ABSTRACT

BACKGROUND: Polystyrene microplastics (PS-MPs) are pervasive pollutants impacting animals across ecosystems, including livestock and wildlife, through contaminated food, water, and air. MPs may disrupt endocrine function, particularly affecting the thyroid gland, which is essential for metabolism and development.

OBJECTIVES: This study investigates the effects of PS-MPs on thyroid function in mice, offering insights relevant to veterinary care by examining changes in gene expression and biochemical markers.

METHODS: PS-MPs of 5 µm diameter were prepared in distilled water after probe sonication. Sixty male Swiss albino mice were divided into three groups: a control group and two treatment groups receiving 0.1 mg and 0.2 mg PS-MPs via oral gavage for 28 days. Mice were anesthetised, and thyroid tissues were collected for histopathological, biochemical, and gene expression analyses. Biochemical tests included catalase, superoxide dismutase, reactive oxygen species, and hormone levels. Histopathology and gene expression (TSHR and TPO) of thyroid-related genes were examined to assess PS-MPs induced effects.

RESULTS: Exposure to PS-MPs in mice led to significant increases in calcium, thyroxin, free T3, free T4, ALP, AST, ALT, and amylase levels, alongside elevated oxidative stress markers. Conversely, the levels of TSH, calcitonin, magnesium and phosphate decreased. Histopathological analysis showed abnormal thyroid follicle development, decrease parafollicular cells, with colloid loss, haemorrhage, and necrosis. Gene expression analysis revealed a marked reduction in TSHR and TPO levels in PS-MPs treated groups, indicating thyroid dysfunction. These findings highlight the profound impact of PS-MPs on thyroid gland function in mice.

CONCLUSION: These findings underscore the potential risks that PS-MPs pose to thyroid health, with potential consequences for other veterinary species. As environmental contamination rises, veterinarians may encounter more endocrine disorders linked to PS-MPs, emphasising the need for further research and preventive measures.

PMID:40367361 | PMC:PMC12077756 | DOI:10.1002/vms3.70393

Ecotoxicol Environ Saf. 2025 May 13;298:118272. doi: 10.1016/j.ecoenv.2025.118272. Online ahead of print.

ABSTRACT

OBJECTIVE: Endocrine-disrupting chemicals (EDCs) can interfere with endocrine function and lead to neurological damage. Neurofilament light chain (NfL) is a protein released into the blood after neuroaxonal damage, and it has become a dependable biomarker for neurological conditions. The study aimed to investigate the associations between single or combined EDCs exposure and serum NfL levels in adults.

METHODS: The 1372 participants included in the study were from the 2013-2014 National Health and Nutrition Examination Survey. Due to the difference in types of EDCs, participants were divided into two populations. Multiple linear regression models were used to assess the association between 32 EDCs and NfL. The least absolute shrinkage and selection operator regression model was used for EDCs selection and the weighted quantile sum (WQS) regression was used for examining the association of EDCs mixture with NfL and identify the predominant exposure.

RESULTS: Levels of urinary bisphenol S, mono(2-ethylhexyl) phthalate, dibutyl phosphate, glyphosate, and 3,5,6-trichloropyridinol were positively associated with serum NfL levels, while benzophenone-3, methylparaben, and propylparaben showed negative associations. In the WQS regression model, the changes of NfL were 0.154 (95 % CI: 0.014-0.294) and 0.164 (95 % CI: 0.033-0.296) for each quartile increase in WQS index of EDCs mixture in the two populations, respectively. Analysis of the subgroup with gender stratification suggested that the association between EDCs mixture and NfL was only significant in men. The positive mixture β was 0.219 (95 % CI: 0.056-0.380) and 0.257 (95 % CI: 0.082-0.433) in the two population, respectively.

CONCLUSION: The study suggested a potential association between single or combined exposure to EDCs and NfL levels. High-level EDCs exposure might be associated with more severe neurological damage, particularly in men.

PMID:40367613 | DOI:10.1016/j.ecoenv.2025.118272

Animals (Basel). 2025 Apr 28;15(9):1249. doi: 10.3390/ani15091249.

ABSTRACT

Cats are different from dogs, and many questions remain open concerning the establishment of pregnancy. In cats, as in dogs, no feto-maternal signaling leading to establishment of pregnancy is known. But as opposed to dogs, the placenta is a source of steroid hormones and corticotropin-releasing hormone (CRH). Scarce information is available on physiological mechanisms at the uterine level during early gestation; more studies are needed on lymphocyte subsets, feto-maternal crosstalk and other mechanisms leading to local immunosuppression, allograft acceptance and embryo nidation and invasion. Recent studies investigate the function of extracellular vesicles (EVs); however, there is no study on embryo- or endometrium-derived EV. During pregnancy, anti-Müllerian hormone (AMH) serum concentrations were found to be higher than in non-pregnant cats, and a recent study found that supraphysiological levels may lead to pregnancy loss; the function of AMH during pregnancy warrants investigation. Most information is available on corpus luteum development and function, showing some similarities to dogs. Some information on maintenance of feline pregnancy was obtained by ovariectomy (OE) or the use of endocrine disruptors, showing that OE does not lead to pregnancy loss in all cases, especially when performed after day 35; the variable effect is still not fully understood. Antiprogesterone, dopamine agonists and prostaglandins were used in different dosages and treatment schemes and showed variable effect during the second half of gestation, highlighting progesterone and prolactin as key hormones for the maintenance of gestation. Some events during early gestation are comparable with the canine species, even though they appear earlier, like the entrance of the zygote into the uterus and implantation; however, significant differences are present concerning the histomorphology of the placenta and, in a few cases, even the gross morphology as in some cats, where the zonary placenta does not completely surround the fetus. Sonographical monitoring of feline pregnancy requires knowledge of species-specific developmental steps and the differential appearance of fetal and maternal structures in comparison with dogs.

PMID:40362064 | PMC:PMC12070954 | DOI:10.3390/ani15091249

Int J Mol Sci. 2025 Apr 24;26(9):4029. doi: 10.3390/ijms26094029.

ABSTRACT

The renin-angiotensin system helps regulate the endocrine system in modulating blood pressure, fluid volume, and body fluid electrolyte levels. The disruption of the renin-angiotensin system can lead to kidney disease onset and progression. However, the mechanism by which kidney angiotensinogen expression and secretion induce the onset and progression of diabetic nephropathy remains unclear. In this study, we used renal proximal tubular epithelial cells, which express high levels of angiotensinogen, to examine food components that regulate angiotensinogen secretion. The renal proximal tubular epithelial cells were first treated with catalase (antioxidant), daidzein, equol (an isoflavone), a MAP kinase inhibitor, ERK, p38, or JNK and then stimulated with hydrogen peroxide. After 24 h, we collected a culture medium to perform an enzyme-linked immunosorbent assay test for angiotensinogen and cells in order to perform real-time PCR to detect angiotensinogen. We found that angiotensinogen secretion increased as the hydrogen peroxide concentration increased. Catalase, daidzein, and equol decreased angiotensinogen expression and secretion. To investigate the cell signaling mechanism involved in these effects, we assessed the contribution of the MAP kinase cascade. Our data suggest the contribution of p38 and JNK. Our study shows that, in proximal tubular epithelial cells, hydrogen peroxide stimulates angiotensinogen secretion. Isoflavones and p38 inhibited angiotensinogen secretion.

PMID:40362266 | PMC:PMC12071920 | DOI:10.3390/ijms26094029

Taiwan J Obstet Gynecol. 2025 May;64(3):469-476. doi: 10.1016/j.tjog.2025.02.003.

ABSTRACT

OBJECTIVE: Bisphenol A (BPA) is an estrogen-like endocrine-disrupting chemical commonly found in various daily consumer products. It causes female reproductive disorders by interfering with endocrine signaling. Normal folliculogenesis, oocyte maturation, ovulation, and luteal growth/involution rely on the gap junctional intercellular communication between granulosa cells (GCs) and oocytes. Connexin 43 (Cx43) is a key gap junction protein in GCs. The expression of Cx43 in GCs is regulated by follicle-stimulating hormone (FSH) at every stage of folliculogenesis. Melatonin, which exerts anti-inflammatory and antioxidative effects, is primarily released by the pineal gland and reproductive cells, including GCs. In this study. We investigated the protective role of melatonin against BPA-induced toxicity in GCs.

MATERIALS AND METHODS: After controlled ovarian stimulation, GCs were collected from patients undergoing in vitro fertilization. To investigate the effect of melatonin on BPA-induced toxicity in GCs, we evaluated biological activity, gene expression, and protein expression in GCs treated with melatonin and BPA.

RESULTS: BPA downregulated the expression of FSH receptor (FSHR) and inhibited the FSH-induced expression of Cx43 in GCs. It also reduced the proportion of FSHR⁺Cx43⁺ cells population in GCs (10.2 %-6.3 %). Melatonin treatment in BPA-treated GCs reversed the BPA-induced downregulation of FSHR expression, restored the FSH-induced expression of Cx43, and the proportion of FSH-increased FSHR⁺Cx43⁺ cells population in GCs (8.6 %-21.3 %).

CONCLUSION: Clinical trials in recent years have shown that melatonin could effectively prevent cell damage, and could also affect reproductive diseases and pregnancy outcomes. Our results elucidated the mechanisms underlying BPA-induced toxicity in GCs. Melatonin may mitigate the adverse effects of BPA on female reproductive function, which are interesting for exploring new targets in the prevention and treatment of reproductive diseases.

PMID:40368516 | DOI:10.1016/j.tjog.2025.02.003

Food Res Int. 2025 Jun;211:116389. doi: 10.1016/j.foodres.2025.116389. Epub 2025 Apr 18.

ABSTRACT

Bisphenol compounds (BPs), particularly bisphenol A (BPA), are chemicals that are widely used in various industrial sections and come into contact with humans via different routes of exposure. Documented toxic effects of BPs include androgenicity, estrogenecity, cytotoxicity, neurotoxicity, etc. As a well-known member of bisphenols, BPA is an endocrine disruptor chemical (EDC) that has been the subject of safety regulations. Monitoring infants' exposure to BPs via consumption of breast milk and infant formula is essential as they are at critical stages of development and are potentially more vulnerable. Following a systematic search in databases PubMed and Scopus, out of 44 studies included in the present work, 27 and 13 analyzed breast milk and infant formula samples, respectively. In addition, 4 studies reported BPs levels in both matrices. BPA is the most frequently detected BP with concentrations in breast milk reaching up to 112.44 ng/g in samples from Taiwan and as high as 262 ng/g in formula samples from Canada. For breast milk and formula samples, Liquid Chromatography coupled with Tandem Mass Spectrometry (HPLC-MS/MS) and Gas Chromatography Mass Spectrometry (GC-MS) were the most frequently employed methods of detection, respectively. Our review indicates scarcity of data on BPA analogs such as bisphenol S (BPS) and bisphenol F (BPF), highlighting the necessity for assessment of the occurrence of all BPA analogs in these matrices.

PMID:40356106 | DOI:10.1016/j.foodres.2025.116389

Environ Health Perspect. 2025 May 13. doi: 10.1289/EHP15574. Online ahead of print.

ABSTRACT

BACKGROUND: Developing human fetuses may be exposed to the chemical compound bisphenol A (BPA), and retinoic acid (RA) has been detected at low levels in water sources. RA signaling regulates key developmental genes and is essential for organ development, including the brain. We previously reported that RA/BPA co-exposure of mouse embryonic stem cells potentiates RA signaling, which warrants further investigation.

OBJECTIVE: This study was undertaken in human induced pluripotent stem cells (iPSCs) and zebrafish embryos to investigate whether co-exposure to BPA and exogenous RA could potentiate HOX gene expression and exert pleiotropic effects on RA signaling.

METHODS: Human iPSCs and zebrafish embryos were exposed to exogenous RA (0, 7.5, 10, or 12.5 nM) or BPA (20 µM) alone or co-exposed to BPA (2 nM-20 µM) and exogenous RA (7.5-100 nM). Post-exposure changes in HOX genes were assessed by quantitative polymerase chain reaction and/or transcriptome analyses. RA receptor antagonists were used to identify the receptor responsible for signaling. In zebrafish, spacial expression of fgf8a and hoxb1a was evaluated by whole-mount in situ hybridization. Mauthner cell and craniofacial cartilage anomalies were studied by immunostaining and Alcian blue staining, respectively. Transcriptome was compared between iPSCs and zebrafish to identify alterations of common biologic processes. Gradient curves of RA signal were calculated to simulate the effects of exogenous RA and BPA in zebrafish.

RESULTS: In both iPSCs and zebrafish, RA/BPA co-exposure had higher expression of 3' HOX genes compared to RA alone; BPA alone had no effect. Addition of RA receptor antagonists abolished these changes. In zebrafish, RA/BPA co-exposure, compared to RA alone, resulted in a significant rostral shift in hoxb1a expression and increased rate of anomalies in Mauthner cells and craniofacial cartilage. Transcriptome comparison and correlations between the experimental results and gradient curve simulations strengthened these observations.

CONCLUSION: Our findings suggested a mechanistic link between chemical exposure and neurodevelopmental impairments, and demonstrated involvement of exogenous RA signaling in endocrine disruption. Further investigation is needed to explore why BPA alone did not affect endogenous RA signaling, whereas exogenous RA signaling was potentiated with RA/BPA co-exposure. https://doi.org/10.1289/EHP15574.

PMID:40359302 | DOI:10.1289/EHP15574

Environ Int. 2025 May;199:109518. doi: 10.1016/j.envint.2025.109518. Epub 2025 May 6.

ABSTRACT

OBJECTIVES: Although previous epidemiological studies have reported the effects of fetal exposure to phthalates and phenols on birth outcomes, evidence is still limited. The objective of this study was to investigate whether prenatal exposure to endocrine-disrupting chemicals [EDCs; phthalates and bisphenol A (BPA)] is associated with birth outcomes and whether there are sex-specific effects.

METHODS: We used data from the Korean CHildren's ENvironmental health Study (Ko-CHENS) cohort. Exposure to phthalates and BPA was measured by urine tests, and the information on outcomes and confounders was obtained from delivery records, biomarker assessment, and a self-reported questionnaire. We performed multivariate logistic regression to estimate the association between exposure to individual phthalates and bisphenol A and birth outcomes. Additionally, to evaluate the effects of EDC mixture exposure, we performed weighted quantile sum regression analysis. Subgroup analysis stratified by maternal age and sex at birth was performed to examine potential differences in associations.

RESULTS: This study included 2,176 mother-child pairs from the Ko-CHENS. We observed a significant association between the risk of PTB and exposure to BPA during early pregnancy and mono-carboxyoctyl phthalate (MCOP) during late pregnancy, with odds ratios of 1.23 (95% CI: 1.01, 1.49) and 1.29 (95% CI: 1.03, 1.62), respectively. Additionally, there was a significant association between exposure to MCOP during early pregnancy and the risk of LBW (OR: 1.39, 95% CI: 1.03, 1.89). For male infants in particular, exposure to MCOP during early pregnancy was associated with the risk of LBW (OR: 2.44, 95% CI: 1.43, 4.15), and exposure to MCOP during late pregnancy was associated with the risk of PTB (OR 1.45, 95% CI: 1.05, 2.02).

CONCLUSIONS: This study suggests a potential association between exposure to BPA during early pregnancy and PTB, while exposure to MCOP during late pregnancy was associated with increased PTB risk in male infants.

PMID:40359600 | DOI:10.1016/j.envint.2025.109518

J Reprod Immunol. 2025 May 8;169:104538. doi: 10.1016/j.jri.2025.104538. Online ahead of print.

ABSTRACT

This review evaluates the role of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in treating obesity-related infertility and recurrent pregnancy loss (RPL). Originally developed for managing type 2 diabetes mellitus (T2DM) and obesity, GLP-1RAs demonstrate potential in improving reproductive outcomes through their metabolic, vascular, and immunological effects. Obesity, a significant contributor to infertility and RPL, disrupts endocrine balance, promotes chronic inflammation, and impairs endometrial receptivity. GLP-1RAs alleviate these challenges by facilitating substantial weight loss, enhancing insulin sensitivity, and modulating immune responses. Research suggests that the immunological benefits of GLP-1RAs extend beyond their weight-loss effects. Key mechanisms associated with their impact on reproductive outcomes include macrophage polarization toward an anti-inflammatory phenotype, suppression of pro-inflammatory cytokine production, and restoration of maternal-fetal immune tolerance through increased regulatory T-cell activity. Emerging evidence highlights their role in enhancing vascularization and reducing oxidative stress at the maternal-fetal interface, critical processes for implantation and placental development. Despite these promising benefits, the use of GLP-1RAs during pregnancy remains contraindicated due to safety concerns. While they show promise in preconception protocols, further clinical trials are needed to establish their efficacy and safety in reproductive health. This review underscores the potential of GLP-1RAs as a multidimensional approach to managing infertility and RPL, particularly in obese women, and advocates for their integration into personalized therapeutic strategies to optimize reproductive outcomes.

PMID:40359784 | DOI:10.1016/j.jri.2025.104538

Environ Pollut. 2025 May 11;376:126422. doi: 10.1016/j.envpol.2025.126422. Online ahead of print.

ABSTRACT

Bisphenol A (BPA) is a chemical compound found in a wide range of everyday consumer products, resulting in human exposure. BPA has been described as an endocrine disruptor, affecting different systems of the human body. Notably, nanomolar levels of BPA have been detected in human matrices, including plasma and milk. BPA exposure has been associated with the development of breast cancer, and the increase in breast cancer incidence prompted us to investigate the effects of BPA in MCF10A, a model of non-transformed mammary epithelium. Cells were treated with 10 nM BPA for 24 h to capture early molecular alterations preceding phenotypic transitions. Comprehensive transcriptomic analyses were conducted to identify differentially expressed genes and enriched signaling pathways. Subsequent validations included assessment of cytokine release, protein expression, immunofluorescence for subcellular localization of Nuclear Factor-Kappa B (NF-κB), and evaluation of actin cytoskeletal organization. Transcriptome analysis revealed enrichment in interleukin signaling and activation of the NF-κB pathway following BPA exposure. Functional assays demonstrated that BPA treatment enhanced cell motility, accompanied by increased phosphorylation of NF-κB. Inhibition of NF-κB effectively mitigated BPA-induced effects, including augmented cell motility, nuclear translocation of NF-κB, and cytoskeletal rearrangements. Notably, inhibition of the Mitogen-Activated Protein Kinase (MAPK) pathway, and to a lesser extent of the AKT pathway, counteracted BPA-induced NF-κB activation and the associated increase in cell motility. In conclusion, we show that nanomolar concentration of BPA induces significant changes in the molecular setting and behaviour of non-tranformed breast cells, activating NF-κB signalling that in turn controls inflammation, cell cycle, proliferation and cell motility. Our findings indicate that nanomolar concentrations of BPA can induce significant molecular and behavioral changes in non-transformed breast epithelial cells. These results contribute to a deeper understanding of how environmental pollutants like BPA may perturb breast epithelial cell function and potentially contribute to carcinogenesis.

PMID:40360080 | DOI:10.1016/j.envpol.2025.126422

Expert Opin Drug Saf. 2025 May 19:1-13. doi: 10.1080/14740338.2025.2505543. Online ahead of print.

ABSTRACT

BACKGROUND: Analgesics are widely used for pain management, yet their association with endocrine dysfunction remains understudied. This pharmacovigilance study analyzes endocrine-related adverse events (AEs) linked to analgesics, identifies high-risk populations, and explores mechanistic pathways.

RESEARCH DESIGN AND METHODS: FAERS data (Q1 2004 to Q3 2023) were analyzed via OpenVigil 2.1 disproportionality analysis to assess analgesic-endocrine AE associations. Risk variations were evaluated through age/gender stratification, and molecular pathways were investigated via enrichment analysis.

RESULTS: Opioids exhibited the strongest endocrine associations, particularly codeine with parathyroid injury (Reporting Odds Ratio [ROR]: 14.867, 95% Confidence interval [95% CI]: 12.336-17.918) and hypothalamic-pituitary injury (ROR: 3.197, 95% CI: 1.52-6.722), and methadone with testicular injury (ROR: 2.126, 95% CI: 1.446-3.126). Flurbiprofen (NSAIDs) exhibited pancreatic injury risk (ROR: 8.416, 95% CI: 5.187-13.656). Gabapentin/pregabalin showed no significant associations. Stratified analyses revealed elevated risks in females (e.g. codeine-parathyroid injury: ROR = 19.028 vs. non-significance in males) and in patients aged ≥ 60 years. Enrichment analysis implicated dysregulated hormone-metabolic pathways underlying tissue-specific injuries and pointed to disruption of several key signaling pathways.

CONCLUSIONS: Specific analgesics (not all) are associated with endocrine risks, particularly in females and older adults, necessitating personalized monitoring despite limited dose-response data.

PMID:40350711 | DOI:10.1080/14740338.2025.2505543

Cureus. 2025 May 11;17(5):e83890. doi: 10.7759/cureus.83890. eCollection 2025 May.

ABSTRACT

Endocrine-disrupting chemicals (EDCs) are widespread environmental contaminants that interfere with hormonal regulation, affecting metabolism, reproduction, neurodevelopment, and overall health. This review presents an overview of recent evidence on the health effects and biological mechanisms of EDCs, with a focus on their impact on hormonal balance and quality of life. An integrative literature review was conducted using 28 peer-reviewed articles published between 2020 and 2025, retrieved from databases such as PubMed, Scopus, and ScienceDirect. The selected studies explored the physiological and pathological effects of EDCs in humans. Compounds, such as bisphenol A, phthalates, and polychlorinated biphenyls (PCBs), can mimic or block hormones, disrupt endocrine signaling pathways, and bioaccumulate in tissues. Exposure, especially during critical developmental windows, is linked to metabolic disorders, infertility, neurodevelopmental delays, and hormone-sensitive cancers. Common exposure sources include food, air, household dust, water, and personal care products. Key mechanisms of action involve receptor binding interference, oxidative stress, and epigenetic alterations. EDCs pose a significant and growing threat to public health, warranting urgent regulatory measures, increased public awareness, and continued research to mitigate long-term health consequences.

PMID:40351481 | PMC:PMC12066167 | DOI:10.7759/cureus.83890

Front Endocrinol (Lausanne). 2025 Apr 25;16:1549988. doi: 10.3389/fendo.2025.1549988. eCollection 2025.

ABSTRACT

PURPOSE: This study aimed to evaluate surgeons' use of intraoperative nerve monitoring (IONM) during thyroidectomy and their approach to loss of signal (LOS) in various clinical scenarios.

MATERIALS AND METHODS: A survey was conducted by the Turkish Endocrine Surgery Society on members of the Society in February 2020 and consisted of 16 questions. The practice of IONM use, rate of inclusion in informed consent texts, and attitudes of participants in case of signal loss were investigated. The study was conducted with 183 participants between February 4-12, 2020.

RESULTS: Most participants (58.2%) had more than 10 years of surgical experience and 36.6% performed more than 50 thyroidectomies annually. IONM was routinely used by 78.7% of the participants, whereas 16.4% reserved its use in difficult cases. Only 5.2% of the participants performed continuous monitoring. In case-based LOS scenarios, the majority of participants (approximately 60%) terminated the operation when the nerve was anatomically intact but LOS persisted, except in high-risk cancer cases. When the nerve anatomy was disrupted, most participants terminated the surgery, except for the high-risk cancer group. In cases of irreversible LOS with preserved nerve integrity, 58.9% of the patients preferred continuous vagus stimulation on the contralateral side, whereas 41.1% preferred intermittent nerve monitoring. Although 68.2% of the participants verbally informed the patients about the risks of LOS, only 24.4% provided this information on the consent form.

CONCLUSION: The use of IONM in thyroid surgery is increasing in our country. However, there is still no consensus on the approach for staged thyroidectomy in cases of signal loss, and institutional and individual differences persist. Further studies are needed to determine the medical-legal implications and effects of these variations.

PMID:40352452 | PMC:PMC12061687 | DOI:10.3389/fendo.2025.1549988

Breast Cancer. 2025 May 12. doi: 10.1007/s12282-025-01718-2. Online ahead of print.

ABSTRACT

BACKGROUND: There is no comprehensive report regarding which patient groups were disrupted by the COVID-19 pandemic in Japan having universal health insurance system. To provide the guidance regarding how to act in future pandemics, we investigated the changes in breast cancer (BC) diagnosis and treatment during the COVID-19 pandemic.

METHODS: The trends of monthly data were calculated in relation to the variables of a total of 291,018 primary BCs registered on the Japanese National Clinical Database between January 2018 and April 2021.

RESULTS: An analysis of the nationwide data during the pandemic showed 9% decrease of newly identified BC compared with before the pandemic. The impact was more relevant in the 40-50, 51-60 and 61-70-years age groups (13%, 8% and 9% decrease, respectively). The most substantial reduction was noted in patients identified through screenings without symptoms with a 17% decrease. These effects were also apparent in cT1, cN0, cStage 0, and cStage I (11%, 9%, 8% and 11% decrease, respectively). In breast surgery procedures, there was a notable decrease in breast-conserving surgery (13%) as well as post-operative radiation therapy (11%). During this period, strategies using neoadjuvant endocrine therapy or chemotherapy were implemented to avoid treatment delays for especially Stage I patients (1.5 folds increase).

CONCLUSIONS: We have identified the patient groups that are more vulnerable to the effects of the pandemic. The changes during the pandemic might provide the guidance regarding how to act in future emergencies to minimize disadvantages for BC patients.

PMID:40353952 | DOI:10.1007/s12282-025-01718-2

J Hazard Mater. 2025 May 9;494:138531. doi: 10.1016/j.jhazmat.2025.138531. Online ahead of print.

ABSTRACT

Despite the strict regulation of short-chain chlorinated paraffins (SCCPs), they continue to be detected in marine environments and organisms worldwide. However, their toxicity to marine fish has been scarcely studied. In this study, the effect of different concentrations of SCCPs (0-1000 μg L⁻¹) on the early life stages of the marine medaka Oryzias melastigma was evaluated. The impacts of SCCPs on the embryonic stage of O. melastigma were considered negligible, while significant growth retardation was observed during the larval stages after 13 days of exposure, with the median lethal concentration (LC₅₀) determined as 227 μg L⁻¹. Exposure to SCCPs for 4 days resulted in melanosome dispersion, immobilization, disruption of feeding activity, and an increase in acetylcholinesterase activity, suggesting that SCCPs induce neurotoxicity in the cholinergic system, leading to mortality through starvation. Dose-dependent DNA damage, fluctuations in mitochondrial respiration, and increases in intracellular reactive oxygen species content and apoptosis were observed after 4 days of exposure, indicating strong induction of oxidative stress. In addition, potential endocrine disruption was observed, as SCCPs significantly decreased cortisol content and modulated the mRNA expressions of genes involved in the hypothalamic-pituitary-interrenal axis. Taken together, exposure to SCCPs resulted in mortality and growth retardation, primarily through neurotoxicity and oxidative stress in marine medaka larvae.

PMID:40354700 | DOI:10.1016/j.jhazmat.2025.138531

J Physiol Pharmacol. 2025 Apr;76(2). doi: 10.26402/jpp.2025.2.01. Epub 2025 May 5.

ABSTRACT

Air pollution is recognised as one of the primary environmental health hazards. The gas molecules including NO₂, CO, SO₂, O₃, particulate matter (PM₁₀, PM_2.5), and volatile organic compounds are being identified as particularly harmful. Despite this, a significant portion of the global population resides in areas with unsatisfactory air quality. Research suggests that air pollutants may act as endocrine disruptors, potentially interfering with thyroid function and contributing thyroid cancer development through oxidative stress, inflammation, and hormonal dysregulation. This paper reviews current literature on the effects of air pollution on thyroid function and thyroid cancer risk, focusing on epidemiological studies and mechanisms of endocrine disruption. Air pollutants are suspected endocrine disruptors that may interfere with thyroid function through receptor binding, hormone displacement, and disruptions in hormone transport, metabolism, and gene expression. Exposure to these pollutants, particularly during fetal development, can impair neonatal thyroid homeostasis, increasing the risk of hypothyroidism and long-term cognitive complications. Prolonged exposure to PM_2.5 has been associated with an increased risk of papillary thyroid cancer (PTC), particularly at higher concentrations and with long-term exposure. Elevated levels of NO₂ and O₃, as well as urban exposure to CO, have also been linked to a heightened risk of thyroid cancer. In contrast, an inverse relationship has been observed for PM₁₀ and SO₂. Additionally, studies suggest a potential association between PM_2.5 exposure and both increased risk and mortality of thyroid cancer, although multiple confounding factors must be considered. Air pollution with PM_2.5, NO₂, CO has also been found to affect thyroid hormone (TH) levels, but findings remain inconsistent, with relationships varying based on age, sex, and internal factors such as obesity. While evidence suggests a link between air pollution and thyroid dysfunction, as well as thyroid cancer risk, inconsistencies in findings highlight the need for further research. A deeper understanding of the mechanisms underlying these associations is crucial to assessing health risks and developing effective public health interventions.

PMID:40350645 | DOI:10.26402/jpp.2025.2.01

BMC Genomics. 2025 May 12;26(1):471. doi: 10.1186/s12864-025-11647-1.

ABSTRACT

BACKGROUND: The regulatory roles of non-coding RNAs (ncRNAs) during sex differentiation in teleosts have received widespread attention recently. Mifepristone (RU486, a progesterone antagonist), which acts as an endocrine disruptor, can affect reproduction and sex differentiation in teleosts.

RESULTS: The expression of ncRNAs in the gonads of tiger puffer (Takifugu rubripes) during RU486 (500 µg/g diet) induced masculinization process was examined by RNA-sequencing. A total of 4,381 long non-coding RNAs (lncRNAs), 309 circular RNAs (circRNAs), and 1,020 microRNAs (miRNAs) were identified. The expression of 41 differentially expressed (DE) lncRNAs and 20 DE miRNAs, which showed sexual dimorphic expression patterns in genetic female gonads in the control group (C-XX) vs. genetic male gonads in the control group (C-XY), were altered in genetic female gonads in the RU486 treated group (RU-XX). The genes targeted by DE ncRNAs were mainly enriched in sex-related pathways, such as calcium signaling, ovarian steroidogenesis, and cortisol synthesis and secretion. The results of co-expression and competing endogenous RNA (ceRNA) network analysis indicated that miRNAs (e.g., miR-205-z and fru-miR-122) and lncRNAs (including XR_003890915.1 and XR_003885862.1) may have pivotal roles, and lncRNAs (including XR_003890295.1, MSTRG.11750.1, and XR_003888827.1) may act as miRNA sponges, involved in the competition between miRNAs and sex-related genes during tiger puffer masculinization process. Dual luciferase reporter assay results identified that ovarian steroidogenesis related gene hsd17b1 is a downstream target of fru-miR-122. The expression of 4 lncRNAs, 4 circRNAs, and 6 miRNAs were validated by qPCR, indicating the accuracy and dependability of RNA-Seq.

CONCLUSIONS: This study provided the evidence that ncRNAs may participate in RU486-induced masculinization in T. rubripes, and may enhance our understanding of the regulatory network of sex differentiation in fugu.

PMID:40355821 | PMC:PMC12067753 | DOI:10.1186/s12864-025-11647-1

Sci Rep. 2025 May 12;15(1):16390. doi: 10.1038/s41598-025-99079-5.

ABSTRACT

Urinary incontinence (UI) significantly impacts the quality of life and psychological well-being of female patients. Although emerging evidence suggests potential links between endocrine-disrupting chemicals and pelvic floor disorders, previous studies on the association between bisphenol A (BPA) exposure and UI in women have yielded inconsistent results. This study aimed to examine this potential association using data from the 2015-2016 National Health and Nutrition Examination Survey (NHANES) (n = 467). Through multiple logistic regression analysis with three adjustment models: Model 1 (crude), Model 2 (adjusted for socio-demographic factors: age, race/ethnicity, education, marital status, and poverty ratio), and Model 3 (further adjusted for BMI, hypertension, diabetes, alcohol/smoking status, and delivery history), we assessed BPA exposure categorized into quartiles. No significant associations were observed between BPA exposure and either stress urinary incontinence (SUI) or mixed urinary incontinence (MUI) across all models (P > 0.05). However, participants in the highest BPA quartile (> 7.6 ng/mg creatinine) exhibited a significantly increased risk of urge urinary incontinence (UUI) in Model 1 (OR = 2.01, 95% CI [1.12-3.63]), Model 2 (OR = 2.04, 95% CI [1.08-3.85]), and Model 3 (OR = 2.48, 95% CI [1.18-5.20]). This study has several limitations, including its cross-sectional design, reliance on self-reported UI outcomes, single measurement of urinary BPA, and potential residual confounding from unmeasured factors. While these findings suggest that environmental BPA exposure may contribute to UUI risk in women, future longitudinal studies with repeated biomarker measurements and objective UI assessments are needed to confirm these observations and explore potential mechanisms. If validated, reducing BPA exposure through public health interventions could emerge as a novel preventive strategy for UUI.

PMID:40355584 | PMC:PMC12069705 | DOI:10.1038/s41598-025-99079-5

J Chromatogr A. 2025 Apr 14;1754:465959. doi: 10.1016/j.chroma.2025.465959. Online ahead of print.

ABSTRACT

Perfumes are chemical cocktails and their effects on humans are complex and diverse. Only selected ingredients are studied, and risk assessment of the perfume is only theoretically carried out at the desk. To close the current gap in the hazard-related analysis of entire perfumes, a sustainable non-target chemical safety screening was developed. The 42 perfumes collected randomly were screened without any sample preparation for ten different adverse effects, i.e., genotoxicity, cytotoxicity, antibacterial activity against Gram-negative and Gram-positive bacteria, neurotoxicity/-modulation, and endocrine-disrupting (aromatase-inhibiting, anti-/estrogenic, and anti-/androgenic) activities. Many hazardous compounds were detected in perfumes, regardless of price or gender-specific use. For example, the half-maximal effective dose (EC₅₀) of genotoxicity was 1.3 µL perfume and the half-maximal aromatase inhibitory dose (IC₅₀) was 11 nL perfume. One 100-µL spray shot of perfume on the skin exceeded the EC₅₀ by 77-fold and the IC₅₀ by 9,090-fold. The new hazard-related profiling of the entire perfumes has provided for the first time in-depth information and significant advances in the understanding of lifestyle products as entry paths for hazardous compounds to the human body. It empowers stakeholders to produce hazard-free perfumes according to ethical statements for the sake of consumer health, authorities to change to a proactive safety screening and address the current underregulation, and scientists to contribute to the global transition towards more sustainable analytical methods and products on the global market.

PMID:40349502 | DOI:10.1016/j.chroma.2025.465959

Toxicology. 2025 May 9;516:154182. doi: 10.1016/j.tox.2025.154182. Online ahead of print.

ABSTRACT

Bisphenol A (BPA) is an endocrine-disrupting chemical that is increasingly becoming a vital factor in public health due to its ubiquity and toxicity. BPA is associated with male infertility via the disrupted function of Leydig and Sertoli cells. Despite extensive research, the current understanding of the specific pathological concentrations and the mechanisms following BPA exposure still remain questionable. Therefore, we investigated the susceptibilities and underlying mechanisms in Leydig and Sertoli cells following treatment with various BPA doses (0.0001-100 µM in a 10-fold serial dilution). Our results showed that the lowest BPA levels (10^-4 μM) decreased mitochondrial membrane potential and ATP levels. In contrast, ROS levels were increased at high BPA levels regardless of exposure time (24 or 48 h) in both cell types. Mitochondrial-mediated apoptosis was identified along with increased ROS levels and abnormal mitochondrial dynamics, but both cell types showed different susceptibility to BPA toxicity. Subsequently, BPA had detrimental impacts on the mRNA expression levels of steroidogenic enzymes and testosterone synthesis in Leydig cells and reduced anchoring junction proteins in Sertoli cells. Consequently, our results demonstrated that both cells were affected via estrogen receptor alpha. However, protein kinase A was oppositely expressed following BPA exposure in each cell type. Therefore, it is plausible to suggest that each cell has distinct sensitivities and mechanisms in response to BPA.

PMID:40349747 | DOI:10.1016/j.tox.2025.154182

J Headache Pain. 2025 May 12;26(1):110. doi: 10.1186/s10194-025-02044-w.

ABSTRACT

Migraine is a complex neurological disorder frequently associated with hypothalamic dysfunction. This brain region is essential for maintaining homeostasis due to its regulation of autonomic, endocrine, and circadian systems. While the pathophysiology of migraine remains incompletely understood, clinical features such as the cyclic nature of attacks and symptoms, including nausea, vomiting, yawning, irritability, and sensitivity to light, indicate a significant role for the hypothalamus. Further, potential triggers of migraine, such as stress and disruption to feeding habits, also impact hypothalamic mechanisms. The higher prevalence of migraine in women compared to men suggests a link to hormonal fluctuations involving estrogen, progesterone, and prolactin. These hormones interact with the hypothalamus, potentially influencing the onset and severity of migraine episodes. Additionally, the hypothalamus synthesizes neuropeptides such as orexins, neuropeptide Y, PACAP, oxytocin, and vasopressin, which are all implicated in migraine mechanisms. Understanding the interplay between the hypothalamus, sex hormones, and neuropeptides offers valuable opportunities for endogenous targeted migraine therapies. In this review we discuss hypothalamic contributions to migraine pathophysiology, highlighting the mechanisms affected by hypothalamic connections, neuropeptides, and hormones, and their role as migraine triggers, particularly focusing on factors like stress, fasting, and changes in sleep patterns.

PMID:40350428 | PMC:PMC12067729 | DOI:10.1186/s10194-025-02044-w

J Cell Mol Med. 2025 May;29(9):e70416. doi: 10.1111/jcmm.70416.

ABSTRACT

Bisphenol A (BPA) is a widely used industrial chemical with potential endocrine-disrupting effects on metabolic processes. This study investigates the impact of BPA on hepatic function and transcriptional regulation in mouse livers and AML12 cells. Male mice were exposed to low (5 g/kg) and high (50 g/kg) doses of BPA for six weeks. Transcriptomic analysis was performed on liver tissues, and histological examinations were conducted. AML12 cells were treated with varying BPA concentrations, and PPARG transcriptional activity was assessed using a luciferase reporter assay. Additionally, molecular docking, molecular dynamics (MD) simulations, drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), MM-PBSA calculations, and multi-species protein structure comparative analysis were employed to analyse the interaction between BPA and PPARG. Transcriptomic analysis revealed a decrease in differentially expressed genes with higher BPA doses, with low-dose exposure significantly downregulating hepatic Cpt1a mRNA levels. Histological examination indicated lipid vacuole formation at high doses without collagen deposition. BPA consistently inhibited PPARG activity in both MCF7 cells and mouse livers. BPA exposure disrupts hepatic lipid metabolism and PPARG activity, highlighting its role as an endocrine disruptor. Further research is needed to elucidate the long-term effects of BPA on liver health.

PMID:40346756 | PMC:PMC12064412 | DOI:10.1111/jcmm.70416

Arch Toxicol. 2025 May 10. doi: 10.1007/s00204-025-04037-9. Online ahead of print.

ABSTRACT

Recently, the European Commission has implemented hazard categories to classify substances as endocrine disruptors for human health, i.e. ED HH 1 or ED HH 2, depending on the weight-of-evidence. However, specific guidance on how to differentiate between the two is unavailable. This article presents the CropLife Europe (CLE) proposal for a structured approach to support the ED HH classification for the thyroid modality. Further, the Thyroid Function-Related Neurodevelopmental Toxicity Testing and Assessment Scheme (Thyroid-NDT-TAS) has been modified in view of the new classification. Application of the CLE proposal and the modified Thyroid-NDT-TAS is illustrated in four case studies covering active substances in plant protection products that showed thyroid- and liver-related effects in laboratory animal studies (pyrimethanil, boscalid, metribuzin, ethiprole). For all four substances, there is strong and consistent evidence that the thyroid-related endocrine activity in rats is liver enzyme induction-mediated, a mode-of-action that is of questionable relevance to humans. In vitro species comparisons (unavailable for pyrimethanil) further confirm non-relevance to humans. However, pyrimethanil (and boscalid) did not elicit developmental neurotoxicity in rats. For pyrimethanil, boscalid and ethiprole, the overall weight-of-evidence determination yields the conclusion "no ED HH via the thyroid modality". For metribuzin, category ED HH 2 may be triggered due to uncertainties related to its database. The case studies underline that expert judgement is required to assess overall effect patterns, to balance the available evidence and to conclude on classification as ED HH 1, ED HH 2 or no ED HH via the thyroid modality.

PMID:40347277 | DOI:10.1007/s00204-025-04037-9

J Hazard Mater. 2025 May 9;494:138546. doi: 10.1016/j.jhazmat.2025.138546. Online ahead of print.

ABSTRACT

Triphenyl phosphate (TPHP) is widely used as a flame retardant and plasticizer in consumer products and is frequently detected in the environment. TPHP competitively binds to estrogen receptors, exhibiting both estrogenic and anti-estrogenic effects, leading to ongoing debate about its role. This study demonstrates that TPHP shows a higher affinity for the estrogen receptor NHR-14 in Caenorhabditis elegans (C. elegans) compared to the typical estrogen estradiol (E2) and the estrogen antagonist 4-hydroxytamoxifen (4-HT). The study also examines the production, distribution, and transport of the estrogen biomarker Vitellogenin family member 2 (VIT-2) following exposure to TPHP, E2, and 4-HT. Environmentally-relevant concentrations of TPHP significantly increased VIT-2 transcription and protein expression levels in C. elegans during early pregnancy, similar to the effects observed with E2. However, during peak pregnancy, TPHP exposure led to abnormal accumulation of VIT-2, primarily due to an increase in the Gibbs Free Energy of the VIT-2_RME-2 complex, which reduced their affinity and subsequently impaired the normal transport of VIT-2. These findings provide novel insights into the toxic mechanisms of TPHP in oviparous animals, highlighting its broader environmental impacts and emphasizing the urgency for further research and regulatory actions to mitigate its risks.

PMID:40347610 | DOI:10.1016/j.jhazmat.2025.138546

J Appl Toxicol. 2025 May 8. doi: 10.1002/jat.4794. Online ahead of print.

ABSTRACT

Bis(2-ethylhexyl) sebacate (DEHS), a commonly used non-phthalate plasticizer considered relatively safe relative to phthalates, has been reported to disrupt the endocrine system, affect reproduction-related genes, and potentially induce thyroid hormone-disrupting and estrogenic effects on Japanese medaka (Oryzias latipes). However, the long-term effects of DEHS exposure on aquatic organisms remain unclear; further, data on residual DEHS concentrations in rivers are extremely limited. Here, the effects of DEHS on the reproductive performance and gonadal sex differentiation of Japanese medaka were determined. Japanese medaka embryos and larvae were exposed to varying DEHS concentrations that have been reported to induce thyroid hormone-disrupting effects. The residual concentrations of DEHS in the Sumiyoshi River were measured weekly from May to July in 2024. The formation of testis-ova was induced in XY medaka exposed to varying DEHS concentrations. DEHS exposure was shown to significantly reduce the number of eggs laid but did not affect fertilization rates. The DEHS levels in the Sumiyoshi River were either undetected or below the method quantification limit. Although significant changes in reproductive capacity and testis-ova were not observed at environmentally relevant residual concentrations, this study highlights the potentially harmful effects of a chemical that was previously considered environmentally friendly.

PMID:40344245 | DOI:10.1002/jat.4794

Birth Defects Res. 2025 May;117(5):e2482. doi: 10.1002/bdr2.2482.

ABSTRACT

BACKGROUND: Anogenital distance and nipple/areola(e) retention are biomarkers for monitoring normal age-appropriate masculinization of male offspring required by U.S. EPA and OECD guidelines for chemicals. OECD Guidance Document 150 considers both landmarks as sensitive, apical endpoints. For the last century, it has been known that nipple regression in male rodents is complete by late gestation and there are no external or microscopic traces of a nipple at the time of birth. Adverse effects of antiandrogen exposures in humans are well documented, and AGD/NR serve as surrogates for effects on physical and sexual development, although the human relevance of these individual endpoints and endocrine disruption in rodents continues to be debated. The European Chemicals Agency (ECHA) published its reports on the EOGRTS Review Project and ranked 37% AGD and 83% NR datasets across 72 studies as limited or of unacceptable quality.

METHODS: We retrospectively analyzed AGD/NR data from 142 rodent studies based on sound scientific principles and per the agency's scoring criteria.

RESULTS AND CONCLUSION: For AGD, our data met standards for precision, variability, and separation of sexes. For NR, our data demonstrated that spontaneous nipple/areolae retention is far less common than asserted by the agency. We propose that the 5-point rating scale used by ECHA to rate NR data has considerable limitations as it is based on data from a single publication that evaluated a limited number of litters/studies. Based on our review of the literature, ECHA recommendations, and the data presented herein, we put forth best practice recommendations for data collection, analysis, and reporting in an effort to improve future data quality, interpretation, and coherence for regulatory review.

PMID:40344521 | DOI:10.1002/bdr2.2482

Food Chem Toxicol. 2025 May 7:115531. doi: 10.1016/j.fct.2025.115531. Online ahead of print.

ABSTRACT

Heavy metals (HMs), particularly lead (Pb) and cadmium (Cd), are hazardous environmental toxicants with toxic effects on female reproductive health. This study investigated the impact of Pb and Cd on mitochondrial energetics in theca interstitial cells (TICs). At their respective EC₅₀ values (15 μM Pb, 5 μM Cd), both metals induced severe mitochondrial impairment, characterized by diminished ATP production and oxygen consumption rates (OCR) alongside loss of mitochondrial membrane potential (MMP). Additionally, Pb and Cd reduced mitochondrial mass, disrupted mitophagy protein expression, and inhibited activities of respiratory chain complexes, paralleled by downregulation of their subunit-coding genes. Both metals elevated lactate production, indicating a metabolic shift toward glycolysis. Structural alterations included increased mitochondrial swelling, enhanced membrane permeability to H⁺ and K⁺ ions, and elevated mitochondrial membrane fluidity (MMF) driven by a higher saturated-to-unsaturated fatty acid ratio. These effects were concentration- and time-dependent. Furthermore, Pb and Cd significantly suppressed progesterone and androstenedione secretion, underscoring endocrine disruption. Collectively, our findings demonstrate that Pb and Cd induce mitochondrial dysfunction in TICs through bioenergetic failure, structural damage, and oxidative stress, providing a mechanistic basis for HM-associated reproductive pathologies. Targeting mitochondrial integrity may offer therapeutic potential for mitigating HM-induced ovarian dysfunction in at-risk populations.

PMID:40345518 | DOI:10.1016/j.fct.2025.115531

Reprod Toxicol. 2025 May 8;135:108943. doi: 10.1016/j.reprotox.2025.108943. Online ahead of print.

ABSTRACT

Octyl methoxycinnamate (OMC), a widely used UV filter, has raised concerns due to its potential reproductive toxicity and association with endocrine disruption. This study systematically identified OMC-induced breast toxicity targets and elucidated underlying molecular mechanisms by integrating network toxicology, differential gene expression analysis, Mendelian randomization (MR), molecular docking, and molecular dynamics (MD) simulations. Using SwissTargetPrediction, OMIM, GeneCards and DisGeNET databases, 185 potential targets linked to OMC exposure and breast injury were identified. STRING and Cytoscape analyses highlighted 31 hub targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment revealed significant associations with immune responses, cell proliferation, and signaling pathways. Analysis of GEO datasets identified overlapping differentially expressed genes (DEGs) between core targets and breast cancer (BC). MR analysis demonstrated a causal relationship between PTGS2 and BC risk. Molecular docking indicated strong binding affinities between OMC and core targets, particularly MMP9. MD simulations further confirmed stable OMC-PTGS2 interactions, supporting PTGS2 as a key mediator of OMC-induced breast toxicity. This work provides a theoretical foundation for understanding OMC's breast toxicity mechanisms and lays groundwork for preventing or managing breast disorders in populations exposed to OMC-containing environments.

PMID:40345629 | DOI:10.1016/j.reprotox.2025.108943

Reprod Sci. 2025 May 8. doi: 10.1007/s43032-025-01873-z. Online ahead of print.

ABSTRACT

This study aimed to investigate the role of fat mass and obesity-associated protein (FTO), an N6-methyladenosine (m⁶A) demethylase, in ovarian aging by examining the effects of FTO downregulation on key biological processes in human ovarian granulosa cells (KGN), including proliferation, apoptosis regulation, senescence, and steroidogenic function. Stable FTO knockdown in KGN cells was achieved using lentivirus, complemented by modeling premature senescence with H₂O₂ treatment. The biological functions, such as cell proliferation, apoptosis, aging, and sex hormone secretion, were assessed using RT-qPCR, WB, EdU staining, and ELISA, respectively. Silencing FTO significantly inhibited the proliferation of KGN cells, promoted apoptosis and senescence, and disrupted their endocrine function. These effects were consistent in the H₂O₂-induced senescence model. Our findings identify FTO as a critical regulator of ovarian homeostasis. Depletion of FTO impairs granulosa cell viability, accelerates senescence-related functional decline, and diminishes steroidogenic capacity through m⁶A-mediated modulation of key biosynthetic enzymes. These insights highlight FTO as a potential therapeutic target for age-related ovarian dysfunction.

PMID:40342080 | DOI:10.1007/s43032-025-01873-z

Environ Geochem Health. 2025 May 9;47(6):202. doi: 10.1007/s10653-025-02518-5.

ABSTRACT

Phthalates (PAEs), a class of typical endocrine-disrupting chemicals, have been widely detected in the environment due to their prevalent use as plasticizers in plastic products. This study investigates the multimedia contamination characteristics and potential ecological risks of PAEs in water, soil, and sediments of the Shaying River (SYR) Basin. A Geodetector model (GDM) was employed to identify the key drivers influencing the spatial distribution of PAEs, while factor analysis and the Positive Matrix Factorization (PMF) model were utilized to quantitatively apportion the potential sources of PAEs. Results revealed that the concentrations and spatial variation of PAEs were significantly higher in soil and sediments than in water, with distinct compositional profiles. Water samples exhibited a higher proportion of low-molecular-weight PAEs compared to soil and sediment, where high-molecular-weight PAEs prevailed to a lesser extent. Notably, among the 6 target PAEs, di-n-butyl phthalate (DBP) and di-(2-ethylhexyl) phthalate (DEHP) were uniformly the primary PAEs in water, soil, and sediment of the SYR Basin, posing higher ecological risks to algae, crustaceans, amphibians, and fish compared to the other 4 PAEs. The spatial distribution of PAEs in the SYR Basin was comprehensively influenced by land use, precipitation, human activities, and soil types. Key factors vary across media, but the interaction between popdensity and other variables significantly enhanced the interpretation degree, jointly shaping the PAEs distribution patterns. Primary sources of PAEs in the basin were sewage and wastewater discharges (37.0%), nonpoint industrial sources (36.4%), and domestic sources (25.6%).

PMID:40343535 | DOI:10.1007/s10653-025-02518-5

Ann Endocrinol (Paris). 2025 May 6:101769. doi: 10.1016/j.ando.2025.101769. Online ahead of print.

ABSTRACT

Prostate cancer is the archetypal hormone-dependent cancer in men, mirroring breast cancer in women. The increase in its prevalence over time raises questions, and occupational exposure data, particularly among agricultural workers, have shown a probable or possible link with exposure to certain endocrine disruptors. The best-known of these is probably chlordecone, used in the French West Indies and responsible for an increased risk of prostate cancer. Outside these situations of massive exposure, it is more difficult to prove that endocrine disruptors are responsible for prostate cancer, particularly through epidemiological studies, the interpretation of which is still difficult. Animal models, in particular murine models, have demonstrated the role of fetal or early neonatal exposure in the development of prostate cancer in adulthood. In vitro models, meanwhile, are shedding light on the mechanisms involved in tumor promotion and progression, involving both classic hormone receptors (AR, ER) and other new signaling pathways. The aim of this review is to report the available data showing the link between exposure to endocrine disruptors and the risk of prostate cancer.

PMID:40339692 | DOI:10.1016/j.ando.2025.101769

Ann Endocrinol (Paris). 2025 May 6:101781. doi: 10.1016/j.ando.2025.101781. Online ahead of print.

ABSTRACT

Exposure to Endocrine disrupting chemicals during critical periods of development can result in detrimental long-term health consequences. The hypothalamus is extremely sensitive to endocrine disrupting chemicals which could participate to the increase in metabolic and reproduction related diseases. We propose the concept according to which exposure to low levels of endocrine disrupting chemicals induces developmental and transgenerational alterations of sexual maturation and energy balance through reprograming of the hypothalamus.

PMID:40339691 | DOI:10.1016/j.ando.2025.101781

Ann Endocrinol (Paris). 2025 May 17;86(3):101787. doi: 10.1016/j.ando.2025.101787. Online ahead of print.

ABSTRACT

Sexual differentiation is highly dependent on the fetal hormonal environment, guiding sexual development and establishing the foundation for lifelong reproductive health. This short communication highlights critical windows of sex determination and differentiation, emphasizing the role of steroid sex hormones, alongside other factors, in orchestrating these processes in early life. Growing evidence suggests that endocrine-disrupting chemicals (EDCs) can disrupt these tightly regulated pathways, leading to developmental disturbances that manifest as reproductive disorders at birth or later in life. In males, disrupted androgen signaling during fetal development is linked to hypospadias, cryptorchidism, reduced fertility, and testicular cancer, while in females, EDC exposure may contribute to altered ovarian function, early puberty, polycystic ovary syndrome (PCOS), and infertility. By illustrating how EDCs can interfere with sexual development, this brief review underscores the need for further research and regulatory measures to mitigate their impact on human health.

PMID:40339696 | DOI:10.1016/j.ando.2025.101787

Ann Endocrinol (Paris). 2025 May 6:101778. doi: 10.1016/j.ando.2025.101778. Online ahead of print.

ABSTRACT

INTRODUCTION: Chimpanzees, our closest relatives, are threatened with extinction by poaching, zoonoses, fragmentation and the destruction of their natural habitat, the tropical forests. The degradation of their habitat due to agricultural expansion and the development of road infrastructures expose them to new risks including pollution.

MATERIAL AND METHODS: Kibale National Park (Uganda) covers 800 km² of mid-altitude forest surrounded by agricultural areas. In the northern part of this protected area, 80% of the perimeter of the Sebitoli chimpanzees' territory is surrounded by human activities (tea, maize and banana plantations, etc.) and crossed by an asphalt road with heavy traffic. In order to study the effects of anthropization on the closest primates to our species, these chimpanzees have been habituated to humans, observed and photographed, and a non-invasive health monitoring has been carried out since 2008. Samples of soil, sediment, water, fish, exhaust gases have been tested for presence of chemicals and plastic bottles along the road were collected. Chimpanzee hair from their nests and urine were also analyzed to assess chimpanzees' exposure to different types of pollution.

RESULTS: Facial congenital deformities and disorders of the female sexual cycle have been observed in Sebitoli chimpanzees. Three successive campaigns showed the presence of a cocktail of chemical pollutants in the rivers that cross their territory. Biological tests of this water show endocrine disruption effects on the thyroid, estrogenic and androgenic axes. Analysis of the chimpanzees' hair showed the presence of 60 pesticide-type molecules, as well as bisphenol A and S, monomers of polycarbonate plastic compounds. Markers of oxidative stress, in particular DNA degradation, were detected in the urine of chimpanzees that frequented the border and consumed maize coated with neonicotinoids.

CONCLUSION: At the heart of tropical forests, wild chimpanzees are exposed to environmental pollution from nearby agricultural areas and the thousands of soda bottles discarded along roadside. The genotoxic oxidative stress, facial malformations and reproductive disorders detected in this community are an alarming signal not only for this species, which is already highly threatened by human activities, but also for our own species. Our research will help to clarify the etiology of these disorders in this sentinel species for our health and that of our environment, and in particular to gain a better understanding of the risks associated with plastics.

PMID:40339695 | DOI:10.1016/j.ando.2025.101778

Ann Endocrinol (Paris). 2025 May 6:101765. doi: 10.1016/j.ando.2025.101765. Online ahead of print.

ABSTRACT

Increased prevalence of developmental defects of enamel reported in recent studies suggests the involvement of novel environmental causal factors. Among them, toxicants with endocrine disrupting activity retain our attention for their ability to disrupt tooth development, notably the synthesis of the two main dental tissues, enamel and dentin, submitted to hormonal control. As dental tissue mineralization follows a well-known sequence of events that starts during fetal life and mostly ends 6 years after birth, with enamel being assimilated to a fossil, dental defects can be considered as good markers of exposure to environmental pollutants especially those with endocrine disrupting activity. The cellular effects and mechanisms of action of some of them, including pro-estrogenic and anti-androgenic compounds, are presented here.

PMID:40339697 | DOI:10.1016/j.ando.2025.101765

Environ Pollut. 2025 May 6;376:126370. doi: 10.1016/j.envpol.2025.126370. Online ahead of print.

ABSTRACT

Due to their use in enabling technologies, rare earth elements and yttrium (REY) have become environmental contaminants, and anthropogenic Gd from Gd-based contrast agents (GBCAs) used in medical diagnostics has become a worldwide concern. Contamination of coastal seawater with GBCAs has previously been documented for the North Sea and the outflow of the Baltic Sea. However, the source(s) of this anthropogenic Gd in the Baltic Sea are not yet known. Hence, we investigated the REY distribution in the Polish rivers Oder and Vistula (and some of their tributaries), which are by discharge the sixth and second largest rivers that enter the Baltic Sea. Large positive Gd anomalies (Gd_SN/Gd∗_SN: 4.92 to 44.6) in all rivers studied reveal the presence of anthropogenic Gd which makes up >90 % of the total Gd inventory of these rivers. Ultrafiltration shows that this Gd is truly dissolved and not associated with nanoparticles and colloids. Hence, its physical speciation is in marked contrast to that of the highly particle-reactive geogenic REY. As this anthropogenic Gd is released from wastewater treatment plants, its presence strongly suggests a high probability of contamination with other waste water-derived substances such as pharmaceuticals, endocrine disruptors and hormones. If artificial groundwater recharge with such surface water would be applied to counterbalance reduced rainfall due to climate change, this would have detrimental effects on drinking water quality. As GBCAs are not removed during estuarine mixing, the Oder and Vistula rivers transport significant amounts of anthropogenic Gd into the Baltic Sea. A rough estimate of the annual flux suggests that these rivers alone account for the input of about 1 ton of anthropogenic Gd per year. Our findings strongly underline the need for continuous monitoring to protect human health and ecological integrity in the Baltic Sea.

PMID:40339880 | DOI:10.1016/j.envpol.2025.126370

Environ Pollut. 2025 May 6;376:126353. doi: 10.1016/j.envpol.2025.126353. Online ahead of print.

ABSTRACT

The production of chemical pesticides poses a critical threat to aquatic ecosystems worldwide, with sub-lethal impacts evident at even relatively low concentrations. Historically, ecotoxicologists have ignored an organism's social context when investigating the effects of pesticide exposure and, instead, have tended to focus on individual-level impacts. Recently, however, there has been a growing interest in understanding the impacts of pesticide exposure on social behaviour. Despite this shift, a holistic understanding of how pesticides impact conspecific interactions (i.e., social behaviour towards individuals of the same species) is lacking due to the multitude of behaviours, pesticides and species currently investigated. In this meta-analysis, we examine the effects of pesticide exposure on conspecific interactions in fish by using data collected from 37 studies on 31 pesticides and 11 species. Our results indicate that pesticide exposure generally reduces the expression of conspecific interactions, but it does not affect the variability of responses between individuals. Courtship behaviour was the most impaired, suggesting that pesticide exposure could weaken how matings are partitioned among individuals in a population. Triazoles and organochlorines were the most impactful pesticide classes for mean differences in behaviour, while triazoles and organophosphates had the greatest effects on response variability. These findings indicate that endocrine-disrupting and neurotoxic pesticides can impact fish conspecific interactions, regardless of their chemical class. Unfortunately, there is a large taxonomic bias in the literature, with most studies using zebrafish as a model, which, in turn, provides scope for studies using a broader range of fish species. We found little statistical evidence of publication biases in our dataset and our results were validated by sensitivity analyses. Overall, our synthesis suggests that pesticides broadly reduce the expression of social behaviours, though effects vary across behaviours, pesticide types, and fish species.

PMID:40339887 | DOI:10.1016/j.envpol.2025.126353

Mol Cell Endocrinol. 2025 May 6;605:112569. doi: 10.1016/j.mce.2025.112569. Online ahead of print.

ABSTRACT

Endocrine-related disorders are highly prevalent globally, affecting millions of people. Such diseases are multifactorial in origin and are influenced by the complex interplay of genetics, lifestyle, and environmental factors. Recurring disruptions in the endocrine homeostasis can lead to a cascade of endocrine-related cancers. It is well known that nuclear receptors (NRs), particularly estrogen receptor and androgen receptor malfunctioning promote the oncogenesis of breast cancer and prostate cancer, respectively. However, existing therapeutics against these diseases, including aromatase inhibitors, (anti-) hormonal therapy, etc., often yield limited success, prompting to explore alternative methods of disease management. Additionally, drug resistance is prominent in cancer patients undergoing multidrug therapy. Currently, novel drug design strategies targeting NRs are being implemented for the discovery of a new generation of small molecule modulators, including selective NR modulators (SNuRMs) and degraders (SNuRDs). Moreover, proteolysis-targeting chimeras (PROTACs) as NR degraders, are also being developed primarily to overcome drug resistance, enhance protein selectivity, and mitigate off-target toxicity. This review highlights recent advancements in SNuRMs and SNuRDs for managing NRs-associated endocrine/metabolic disorders. Furthermore, we discuss the therapeutic potential of PROTAC degraders as a stand-alone strategy for receptor-mediated disease intervention, offering new avenues for precision medicine.

PMID:40339978 | DOI:10.1016/j.mce.2025.112569

Environ Res. 2025 May 6;279(Pt 1):121796. doi: 10.1016/j.envres.2025.121796. Online ahead of print.

ABSTRACT

Anxiety Disorder is a common neurological disorder for which ubiquitous environmental endocrine disruptors may be risk factors. 17β-trenbolone (17-TB) has been recognized as a potential environmental endocrine disruptor and its neurotoxic effects have attracted attention. Tachykinin receptor 3 (TACR3), a G protein-coupled receptor involved in pubertal anxiety, and its underlying neural mechanisms remain enigmatic. Therefore, this study investigated the possible relationship between 17-TB and TACR3, testosterone (T), and synaptic plasticity. Our results showed that adolescent male Balb/c mice developed significant anxiety-like behavior after four weeks of exposure to environmentally relevant concentrations of 17-TB (100 μg/kg/day). Transcriptomic RNA-Seq results showed that 17-TB affected abnormal synaptic transmission signals in the hippocampus. Electrophysiological results showed that 17-TB reduced the activity of hippocampal dentate gyrus (DG) neurons and led to the downregulation of hippocampal TACR3 and T levels. In addition, Western blot, immunohistochemistry, ELISA, and qRT-PCR showed that 17-TB exposure led to the downregulation of key hippocampal synaptic proteins PSD95, Gephyrin, and Syn, and induced a metabolic imbalance in glutamate (Glu)/GABA signaling, affecting dopamine signaling. Interestingly, testosterone supplementation (10 mg/kg/day) was effective in ameliorating the above phenomena and alleviating anxiety-like behaviors. These results suggest that 17-TB modulates anxiety-related synaptic plasticity by regulating hippocampal TACR3 and T interactions in vivo. In conclusion, our study contributes to understanding the neurobehavioral and potential mechanistic effects of environmental 17-TB exposure in mammals. It alerts the public to the health risks of chemicals to mammals and suggests new research directions and potential therapeutic targets.

PMID:40340005 | DOI:10.1016/j.envres.2025.121796

Int J Environ Health Res. 2025 May 8:1-13. doi: 10.1080/09603123.2025.2502636. Online ahead of print.

ABSTRACT

In recent years, the health impacts of phthalates and bisphenol-A (BPA) have garnered significant research attention due to their widespread use in consumer products and identification as endocrine disrupting chemicals (EDCs). Human exposure occurs through various pathways, including dietary intake, inhalation of dust, and dermal contact. This study initially aimed to analyze serum samples from 200 participants in Jabalpur city (Central India); however, samples from 173 individuals were ultimately analyzed to assess the occurrence, concentration patterns, and gender-related differences of six phthalates and BPA. Serum samples were collected, processed, and analyzed for EDC content using gas chromatography coupled with mass spectrometry. The findings highlighted differences in detection frequencies among genders and residential areas, shaped by environmental exposure variability, lifestyle variations, and gender-specific metabolic disparities. All the targeted analytes were detected with diethyl phthalate (DEP) having the highest mean concentration of 13.74 ± 6.2 ng/ml, followed by di(2-ethylhexyl) phthalate (DEHP) with mean value of 13.69 ± 99.82 ng/ml in human serum. Studies have linked DEP exposure endocrine disruption and reproductive abnormalities. Subsequent research endeavors should prioritize elucidating EDC sources, pathways, and health impacts, facilitating evidence-based policies to mitigate risks and ensure a healthier future.

PMID:40337983 | DOI:10.1080/09603123.2025.2502636

J Diabetes Metab Disord. 2025 May 3;24(1):113. doi: 10.1007/s40200-025-01617-5. eCollection 2025 Jun.

ABSTRACT

BACKGROUND: Type 2 diabetes mellitus (T2DM) develops primarily from obesity as leptin (LEP) functions as an essential adipokine that controls metabolic regulation, energy balance activities, and glucose maintenance. The T2DM and obesity susceptibility traits are believed to be affected by genetic variations in the leptin receptor gene (LEPR), disrupting LEP signaling mechanisms. This case-control study investigates the association of these variants with T2DM risk in a Southeastern Iranian population.

METHODS: A case-control study was conducted involving 450 T2DM patients and 450 matched healthy controls from Zahedan. Genomic DNA for this study was isolated from peripheral blood samples, and genotyping for the specified LEPR rs1137100, rs1137101, and rs1805094 polymorphisms was conducted using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Computational analysis created a gene-gene interaction network, highlighting LEPR as a central hub gene and detailing its interactions with related genes.

RESULTS: Genetic models, such as codominant heterozygous (p-value = 0.009), dominant (p-value = 0.006), recessive (p-value = 0.008), and allelic (p-value = 0.011), all showed that the rs1137100 (A/G) polymorphism lowered the risk of T2DM. Several genetic models linked polymorphisms at the rs1137101 (G/A) and rs1805094 (G/C) loci to a higher risk of T2DM: The genetic models that were looked at were polymorphism rs1137101 (G/A) in codominant Homozygous (p-value = 0.031) and recessive (p-value = 0.028), as well as polymorphism rs1805094 (G/C) in codominant heterozygous (p-value = 0.009), dominant (p-value = 0.001), excess (p-value = 0.008), and allelic (p-value = 0.001). The research demonstrated a profound linkage disequilibrium (LD) among studied variants, especially in the LEPR haplotypes and across various blocks, with differing levels of association strength. The gene-gene interaction network for the LEPR gene highlights its strong associations with several key regulatory genes: LEP, PTPN11, STAT3, POMC, JAK2, IL6, and SOCS3.

CONCLUSION: We found a significant correlation between LEPR gene polymorphisms and the risk of T2DM, highlighting the prominent role of genetic factors in developing such a metabolic disorder. By elucidating the association between LEPR variations and susceptibility to T2DM, our findings enhance the understanding of molecular mechanisms involved in endocrine dysregulation and highlight the importance of including genetic profiling in clinical practice.

PMID:40331155 | PMC:PMC12049348 | DOI:10.1007/s40200-025-01617-5

Clin Interv Aging. 2025 Apr 29;20:513-522. doi: 10.2147/CIA.S513910. eCollection 2025.

ABSTRACT

PURPOSE: Recent advancements in psycho-neuro-endocrine-immunology indicate that numerous noncommunicable diseases (NCDs) originate from disruptions in the cytokine immune network, resulting in chronic inflammatory responses. This persistent low-degree inflammation is attributed to deficiencies in crucial endogenous anti-inflammatory neuroendocrine systems, including the pineal gland, the endocannabinoid system, and the angiotensin-converting enzyme 2 / angiotensin 1-7 axis. The administration of pineal methoxyindoles (melatonin, 5-methoxytryptamine), cannabinoids, and angiotensin 1-7 may entail potential therapeutic benefits for NCDs, particularly for patients who do not respond to conventional treatments.

PATIENTS AND METHODS: This study evaluates the safety and efficacy of a neuroimmune regimen comprising melatonin (100 mg/day at night), 5-methoxytryptamine (30 mg in the early afternoon), angiotensin 1-7 (0.5 mg twice daily), and cannabidiol (20 mg twice daily) in 306 patients with NCDs, including advanced cancer, autoimmune diseases, neurodegenerative disorders, depression, and cardiovascular disease.

RESULTS: The neuroimmune regimen successfully halted cancer progression in 68% of cancer patients, who also reported improvements in mood, sleep, and relief from anxiety, pain, and fatigue. In patients with autoimmune diseases, the treatment effectively controlled the disease process, remarkable in cases of multiple sclerosis. Additionally, positive outcomes were observed in patients with Parkinson's disease, Alzheimer's disease, and depression.

CONCLUSION: Randomized controlled trials are required to assess this therapeutic approach for NCDs that includes endogenous neuroendocrine molecules regulating immune responses in an anti-inflammatory manner.

PMID:40330271 | PMC:PMC12050209 | DOI:10.2147/CIA.S513910

Aging Clin Exp Res. 2025 May 7;37(1):143. doi: 10.1007/s40520-025-03052-1.

ABSTRACT

Urbanization is reshaping global health, with over 55% of the world's population residing in urban areas, a figure projected to reach 68% by 2050. This demographic shift presents significant challenges and opportunities for public health, as urban environments exacerbate health disparities rooted in social determinants of health, such as economic stability, education, neighborhood conditions, and access to healthcare. Rapid urban growth, particularly in low- and middle-income countries, has led to the emergence of inequitable living conditions, environmental hazards, and limited access to essential health services, contributing to the early onset of multimorbidity and rising non-communicable disease burdens. Urbanization-driven factors such as obesogenic environments, sedentary lifestyles, air pollution, and inadequate sleep exacerbate cardiovascular and metabolic risks, while social exclusion, overcrowding, and inadequate mental health services heighten vulnerabilities. Emerging risks, including urban heat islands, noise pollution, and exposure to endocrine-disrupting chemicals, further compound urban health inequities. Effective mitigation requires multi-sectoral policies that prioritize health-promoting infrastructure, reduce environmental pollutants, foster equitable healthcare access, and address systemic barriers affecting marginalized groups. This review explores the intersections between urbanization and health inequities, emphasizing the importance of addressing traditional and emerging risk factors across the lifespan. Policy implications include promoting green infrastructure, enhancing urban mobility, expanding mental health care, and leveraging participatory governance to foster resilient and inclusive cities. By adopting an integrated approach that prioritizes social equity and sustainability, cities can mitigate health disparities and create healthier, more inclusive urban environments that support the well-being of all residents.

PMID:40332678 | PMC:PMC12058932 | DOI:10.1007/s40520-025-03052-1

Fish Physiol Biochem. 2025 May 7;51(3):91. doi: 10.1007/s10695-025-01508-9.

ABSTRACT

Fipronil (FPN) as an insecticide can excessively enter aquatic ecosystems and may act as endocrine-disrupting chemicals by binding to estrogen receptor (ER) or aryl hydrocarbon receptor (AhR). Currently, there is limited information on the xenoestrogen role of FPN in the transcriptional modulation of hepatic genes involved in cell apoptosis. Three experiments were used in this study to determine how the FPN interference between the ER, AhR, and intermediate chaperons can induce apoptosis and change the expression of erα, erβ, erβ2, hsp70, hsp90, p53, bad1, bcl2, ahr, cyp1a, and caspase9 genes in common carp (Cyprinus carpio) hepatocytes. The IC₅₀ values of FPN and 17β estradiol (E2) (positive control) in fish hepatocytes were determined (5 µg/mL). In the first experiment, exposure (6, 24, and 48 h) of hepatocytes to the low (0.1 µg/mL) and high (1 µg/mL) doses of FPN up-regulated apoptosis, pro-apoptotic genes (caspase9 and bad1), and chaperone protein genes (hsp70 and hsp90), while down-regulated anti-apoptotic genes (p53and bcl2). Additionally, there was a significant increase in the expression of the genes erα, ahr, and cyp1a that was dependent on both time and dose. ERα antagonist and a high dose of FPN were administered to the hepatocytes in the second experiment, which reduced cell apoptosis. In the third experiment, anti-apoptotic gene expression increased, and cell apoptosis and ahr and cyp1a gene expression significantly decreased when HSP90 and ERα antagonists were applied in comparison to the control group (P < 0.05). Based on this study, we demonstrate that FPN-induced apoptosis in fish hepatocytes is mediated by erα and hsp90 through transcriptional regulation of pro-apoptotic and anti-apoptotic genes.

PMID:40332693 | DOI:10.1007/s10695-025-01508-9

Int J Mol Sci. 2025 Apr 20;26(8):3896. doi: 10.3390/ijms26083896.

ABSTRACT

Bisphenol A (BPA) is the most used widely synthetic compound for the manufacture of polycarbonate plastics and epoxy resins produced worldwide. Given its androgenic and estrogenic activities, BPA is an endocrine disruptor that is linked to neurological and vascular outcomes, including strokes. Therefore, this study aims to investigate the mechanisms by which a 24 h exposure to BPA (0.002-20 μM) modifies the contractile function of rat middle cerebral artery (MCA) smooth muscle cells (SMCs). Thus, MCA explants were isolated from Wistar rats, and the SMC-MCA vasoactive response was assessed using planar cell surface area, while the gene expression of proteins and ion channel subunits involved in the MCA vasoactive response was evaluated by real-time quantitative PCR. The exposure to BPA (0.02 and 2 μM) decreased the noradrenaline (NA) vasocontractile response and sodium nitroprusside (SNP) vasorelaxant response. Moreover, exposure to BPA (0.02 and 2 μM) increased the gene expression of the soluble guanyl cyclase protein and the large conductance Ca²⁺-activated K⁺ channels (1.1 α-subunit). These results suggest an impairment of the SMC-MCA vasoactive response induced by intermediate BPA concentrations, an effect not attained for the lowest or highest exposure concentrations (non-monotonic inverted U-shaped response). In summary, these findings suggest that BPA exposure modifies MCA vascular homeostasis by interfering with the nitric oxide (NO) pathway and may, thus, be involved in ischemic stroke development.

PMID:40332806 | PMC:PMC12027836 | DOI:10.3390/ijms26083896

J Steroid Biochem Mol Biol. 2025 Jul;251:106773. doi: 10.1016/j.jsbmb.2025.106773. Epub 2025 May 5.

ABSTRACT

Polycystic Ovary Syndrome (PCOS) is a common endocrine syndrome characterized by hormonal imbalances, metabolic disturbances, and clinical symptoms. The pathophysiology of this syndrome involves disruptions in hormonal signaling, particularly changes in levels of luteinizing hormone (LH), and follicle-stimulating hormone (FSH) which can lead to anovulation and infertility. Additionally, insulin resistance and dysfunctional adipose tissue are other complicating factors of this condition. Biochemical markers such as FSH, LH, lipid profiles, and adipokines (like leptin and adiponectin) are crucial for diagnosing PCOS and assessing its severity. In PCOS patients, elevated LH levels relative to FSH are typically observed, and lipid abnormalities increase the risk of cardiovascular diseases. Diagnosing this syndrome usually requires comprehensive biochemical tests to confirm hyperandrogenism and insulin resistance. Management strategies include lifestyle modifications and pharmacological interventions aimed at correcting hormonal imbalances and dyslipidemia. Monitoring treatment outcomes through biochemical markers is essential for evaluating therapeutic efficacy. This review article examines the roles of FSH and LH hormones, lipids, and adipokines in the diagnosis and management of PCOS, emphasizing the importance of clinical biochemistry in improving diagnostic and treatment methods for this disorder. Furthermore, research into identifying emerging biomarkers for early diagnosis and new therapeutic targets is suggested.

PMID:40334996 | DOI:10.1016/j.jsbmb.2025.106773

Environ Sci Technol. 2025 May 20;59(19):9412-9425. doi: 10.1021/acs.est.4c13485. Epub 2025 May 7.

ABSTRACT

Declines in reptile populations due to climate warming and environmental pollution have been documented. Although recent ecotoxicological studies of reptiles have increased, little is known about how these two stressors interact to affect reptile reproductive processes. This study investigated the single and combined effects of atrazine and warming on reproduction in female lizards (Eremias argus) following 10 weeks of exposure to environmentally relevant concentrations of atrazine (0-10 mg·kg^-1) at two temperature treatments (control or warming). Reproductive traits, clutch characteristics, and endpoints related to endocrine disruption (HPG axis gene expression) and energy metabolism (enzyme activity, hepatic metabolomics) were assessed. Atrazine inhibits female reproduction by disrupting HPG axis-related gene expression and energy metabolism, resulting in delayed spawning time and reduced fecundity. In contrast, warming promoted female reproduction and partly alleviated the inhibitory effects of atrazine, which is related to the upregulation of HPG axis-related gene expression and an additional energy metabolism compensatory response. Additionally, atrazine and/or warming altered the direction and intensity of the trade-off between egg number and size and affected maternal nutritional investment in eggs. These findings highlight the complex interplay of environmental stressors on lizard reproduction and add to a better understanding of reptile reproductive strategies and ecological consequences under environmental stress.

PMID:40335436 | DOI:10.1021/acs.est.4c13485

Environ Sci Technol. 2025 May 6. doi: 10.1021/acs.est.5c02446. Online ahead of print.

ABSTRACT

Despite structural and functional conservation across vertebrate species, the glucocorticoid receptor has been minimally studied in comparison to other biological targets for endocrine-disrupting compounds in aquatic systems. Because prolonged use of pharmaceutical glucocorticoids in humans has been linked to osteoporosis and impaired bone growth, we hypothesized that the ability of teleost fish to regenerate fins following damage may be inhibited by exposure to synthetic glucocorticoids in the environment. In the present study, we examined fin regeneration following a 7 days waterborne exposure of juvenile fathead minnows (Pimephales promelas) to the synthetic glucocorticoids, fluticasone propionate and dexamethasone. Expression of several biologically relevant gene products (sgk1, tdgf1, runx2a, lef1, shha, and tsc22d3) was measured in paired caudal fin and whole-body tissues. Fluticasone propionate and dexamethasone significantly impaired fin regeneration at measured water concentrations of 2.62 μg/L and 4.62 mg/L, respectively. Changes in gene expression indicated disruption of intercellular communication in the Wnt/β-catenin and bone morphogenetic protein (BMP) signaling pathways after exposure to 4.86 μg/L fluticasone propionate. Upregulation of tsc22d3, a transcription factor responsible for suppression of anti-inflammatory response, may be the plausible cause of repressed cellular signaling. These findings advance the development of adverse outcome pathway 334─Glucocorticoid Receptor Activation Leads to Impaired Fin Regeneration─and elucidate both the mechanistic relationship between activation of the glucocorticoid receptor by fluticasone propionate and inhibition of fin regeneration, which could plausibly reduce individual fitness in aquatic systems.

PMID:40326831 | DOI:10.1021/acs.est.5c02446

Appl Microbiol Biotechnol. 2025 May 7;109(1):112. doi: 10.1007/s00253-025-13480-8.

ABSTRACT

Estrogens, particularly 17β-estradiol, are prevalent endocrine-disrupting chemicals in aquatic environments, posing risks to ecosystems and human health. Biodegradation is considered one of the most effective and environmentally friendly methods for removing estrogen. In this study, a novel bacterial strain, Microbacterium proteolyticum ZJSU01, was isolated from pig manure. It completely degraded 5 mg/L of 17β-estradiol (E2) within 4 h, as well as its major transformation product, estrone (E1). The strain ZJSU01 displayed strong adaptability to high temperatures (37℃, 42℃) and a broad pH range (6-11), E2 (5 mg/L) could be completely removed by the strain under these conditions. Transformation intermediates were analyzed using UHPLC and HPLC-Q-TOF-MS to identify key metabolites and trace the degradation pathways. Four potential degradation pathways were identified, including the 4,5-seco pathway, which is widely conserved in most E2-degrading bacteria. Whole-genome sequencing predicted a chromosome with a size of 3,828,432 bp, and a series of functional genes, and transcriptomics analysis identified several genes involved in E2 degradation. The budC gene, a member of the short-chain dehydrogenases/reductases (SDRs) family, was identified as critical for E2 degradation and exhibited a nearly 170-fold upregulation. Meanwhile, genes such as fdeE and catA were associated with downstream degradation. Microbacterium proteolyticum ZJSU01 demonstrated strong acid-base and high-temperature resilience, highlighting its strong potential for practical applications due to its degradation capability and adaptability. This strain could be applied in wastewater treatment to effectively remove estrogenic pollutants from contaminated water. KEY POINTS: • Microbacterium proteolyticum ZJSU01 removed 100% of E2 (10、5、1 mg/L) within 4 h. • Strain ZJSU01 showed great tolerance to high temperature and acid-base conditions. • A novel gene, budC, was identified as the primary driver of E2 degradation by ZJSU01.

PMID:40329093 | PMC:PMC12055944 | DOI:10.1007/s00253-025-13480-8

Sci Rep. 2025 May 6;15(1):15814. doi: 10.1038/s41598-025-96135-y.

ABSTRACT

The complex genetic mechanisms underlying human ovary development can give rise to clinical phenotypes if disrupted, such as Primary (or Premature) Ovarian Insufficiency and Differences of Sex Development. We combine single-nuclei RNA sequencing, bulk RNA sequencing, and micro-focus computed tomography to elucidate the anatomy and transcriptional landscape of the human fetal ovary across key developmental timepoints (Carnegie Stage 22 until 20 weeks post conception). We show the marked growth and distinct morphological changes within the fetal ovary at the critical timepoint of germ cell expansion and demonstrate that the fetal ovary becomes more transcriptomically distinct from the testis with age. We describe previously uncharacterised ovary developmental pathways, relating to neuroendocrine signalling, energy homeostasis, mitochondrial networks, and inflammasome regulation. We define transcriptional regulators and candidate genes for meiosis within the developing ovary. Together, this work advances our fundamental understanding of human ovary development and has relevance for human ovarian insufficiency phenotypes.

PMID:40328871 | PMC:PMC12055976 | DOI:10.1038/s41598-025-96135-y

J Environ Sci Health C Toxicol Carcinog. 2025;43(2):184-207. doi: 10.1080/26896583.2025.2498831. Epub 2025 May 6.

ABSTRACT

The cosmetic and personal care product (PCP) industries have bloomed in the last ten years. Many new brand names have established themselves with various lucrative advertisements, luring youths into their primary customers. Many chemicals infused into daily day-night creams or shampoo conditioners have been established as Endocrine Disrupting Chemicals (EDC). The unseen side of the coin has been flipped in this article in an attempt to relate the rising infertility issue with these products. The study aims to explore the potential adverse effects and risk assessment of the EDCs of cosmetics and personal care products, which highlights a thorough review to indicate whether chemicals such as parabens, phthalates, or UV filters are safe for reproductive physiology. EDCs may cause severe negative impacts on the reproductive systems of both males and females which include reproductive problems such as polycystic ovarian syndrome, hypospadias, cryptorchidism, ovarian cancer, endometriosis, and poor sperm quality. Despite the widespread usage and purchase of cosmetic products in the present world, little research has been conducted on the possible effects of cosmetic EDCs on health. Consequently, further in-depth research needs to be performed in this field for a better understanding of the reproductive risks caused by cosmetic EDCs.

PMID:40326240 | DOI:10.1080/26896583.2025.2498831

J Endocr Soc. 2025 Apr 15;9(6):bvaf066. doi: 10.1210/jendso/bvaf066. eCollection 2025 Jun.

ABSTRACT

CONTEXT: Bisphenol A (BPA) and its analogues disrupt endocrine functions, adversely impacting oocyte meiosis, maturation, and granulosa cell (GC) steroidogenesis.

OBJECTIVE: To identify clinical factors, particularly adiposity and age, influencing ovarian cell sensitivity to bisphenol (BP) exposure.

METHODS: This study analyzed a cohort of 368 women undergoing assisted reproductive technology (ART) from 2019 to 2023. Four BPs (BPA, BPS, BPF, and BPAF) were quantified, and ART outcomes (eg, oocyte count, embryo quality, and pregnancy rates) were assessed using regression models. GCs from 156 patients were cultured and exposed to BPS for 48 hours to evaluate progesterone and estradiol secretion based on clinical parameters.

RESULTS: BPS and BPA were the most prevalent BPs in follicular fluid. BP exposure was associated with reduced fertilization rates (P = .05). Obesity tended to lower live birth rates (P = .08) but did not affect embryo development or implantation. Age significantly impacted embryo quantity (P < .001) and quality (P = .03). GC progesterone secretion was correlated with donor age after exposure to 1 µM and 10 µM BPS (P = .03 for both). GCs from younger women appeared more sensitive to BPS.

CONCLUSION: Although obesity did not affect embryonic development, its association with reduced live birth rates suggests a suboptimal environment for implantation and/or fetal development. Age was linked to lower antral follicle count, pregnancy rates, and live birth rates. Younger women's GCs may exhibit heightened sensitivity to BPS exposure, warranting further investigation.

PMID:40321171 | PMC:PMC12046224 | DOI:10.1210/jendso/bvaf066

Anal Bioanal Chem. 2025 May 5. doi: 10.1007/s00216-025-05886-0. Online ahead of print.

ABSTRACT

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) possess water-repellent, oil-repellent, and heat-resistant properties, making them widely used in consumer goods and industrial products. However, PFASs have been increasingly associated with health concerns, including reproductive toxicity, endocrine disruption, and thyroid disease. In 2023, the US consumer platform "Mamavation" reported organic fluorine levels ranging from 105 to 20,700 ppm in 18 contact lenses, raising concerns about the potential presence of PFASs in these products. Given the absence of established international testing methods and regulatory limits for PFASs in contact lenses, this study evaluated nine standard international methods, ultimately selecting 49 PFASs as target analytes after eliminating overlaps. To facilitate detection, novel extraction methods were developed for contact lenses and their lens care solutions. Ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed for analysis, utilizing an analytical column (Atlantis Premier BEH C18 AX, 1.7 µm, 2.1 × 100 mm) and an isolator column (Atlantis Premier BEH C18 AX, 5 µm, 2.1 × 50 mm) to minimize background interference. Electrospray ionization in combination with multiple reaction monitoring mode enabled rapid analysis within 24 minutes. For contact lenses, the limit of quantification (LOQ) ranged from 1 to 400 ng/g, while for lens care solutions, the LOQ ranged from 0.04 to 0.8 ng/mL. When applied to 12 contact lens samples, the method detected 6:2 FTS (1H,1H,2H,2H-perfluorooctane sulfonic acid) in only one lens care solution at a concentration of 0.087 ng/mL. This study highlights the importance of further investigation into PFAS contamination in contact lenses and the need for international standardization in testing methodologies.

PMID:40323375 | DOI:10.1007/s00216-025-05886-0

Anal Bioanal Chem. 2025 May 5. doi: 10.1007/s00216-025-05886-0. Online ahead of print.

ABSTRACT

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) possess water-repellent, oil-repellent, and heat-resistant properties, making them widely used in consumer goods and industrial products. However, PFASs have been increasingly associated with health concerns, including reproductive toxicity, endocrine disruption, and thyroid disease. In 2023, the US consumer platform "Mamavation" reported organic fluorine levels ranging from 105 to 20,700 ppm in 18 contact lenses, raising concerns about the potential presence of PFASs in these products. Given the absence of established international testing methods and regulatory limits for PFASs in contact lenses, this study evaluated nine standard international methods, ultimately selecting 49 PFASs as target analytes after eliminating overlaps. To facilitate detection, novel extraction methods were developed for contact lenses and their lens care solutions. Ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed for analysis, utilizing an analytical column (Atlantis Premier BEH C18 AX, 1.7 µm, 2.1 × 100 mm) and an isolator column (Atlantis Premier BEH C18 AX, 5 µm, 2.1 × 50 mm) to minimize background interference. Electrospray ionization in combination with multiple reaction monitoring mode enabled rapid analysis within 24 minutes. For contact lenses, the limit of quantification (LOQ) ranged from 1 to 400 ng/g, while for lens care solutions, the LOQ ranged from 0.04 to 0.8 ng/mL. When applied to 12 contact lens samples, the method detected 6:2 FTS (1H,1H,2H,2H-perfluorooctane sulfonic acid) in only one lens care solution at a concentration of 0.087 ng/mL. This study highlights the importance of further investigation into PFAS contamination in contact lenses and the need for international standardization in testing methodologies.

PMID:40323375 | DOI:10.1007/s00216-025-05886-0

Endocrinology. 2025 Apr 22;166(6):bqaf087. doi: 10.1210/endocr/bqaf087.

ABSTRACT

High levels of exposure to di(2-ethylhexyl) phthalate (DEHP), a known endocrine disruptor, have been linked to adverse pregnancy outcomes, yet the mechanisms by which it impacts human uterine functions remain unclear. Here we report that exposure of differentiating primary human endometrial stromal cells (HESCs) to an environmentally relevant concentration of DEHP or its primary metabolite, mono(2-ethylhexyl) phthalate, markedly reduces the expression of the estrogen-regulated transcription factor hypoxia-inducible factor 2-α (HIF2α). We also noticed a simultaneous decrease in RAB27B expression, which is crucial for the trafficking and secretion of extracellular vesicles (EVs). EVs enhance communication among various cell types within the pregnant uterus, thereby ensuring reproductive success. We found that estrogen receptor α (ERα) could no longer bind to the HIF2α regulatory region following phthalate treatment, and epigenetic analysis suggested that this may be due to hypermethylation of nearby CpG islands. Further investigation revealed a potential interaction between ERα and the transcription factor specificity protein 1 (Sp1) within the HIF2α regulatory region, which is affected by the inhibition of Sp1 binding to the phthalate-induced hypermethylated DNA. Additionally, our results suggest that the abnormal DNA methylation is likely due to increased expression of the DNA methyltransferase 1 (DNMT1) gene in response to phthalate exposure. Overall, this study provides valuable mechanistic insights into how phthalate-induced differential DNA methylation disrupts estrogenic regulation of the HIF2α gene and, consequently, EV secretion during HESC differentiation. This knowledge is essential for understanding how phthalates may lead to adverse reproductive outcomes by disrupting hormonal regulation of cell-to-cell communication in the uterus.

PMID:40323777 | PMC:PMC12075775 | DOI:10.1210/endocr/bqaf087

Reprod Toxicol. 2025 May 3;135:108931. doi: 10.1016/j.reprotox.2025.108931. Online ahead of print.

ABSTRACT

The mammary gland undergoes dramatic changes during pregnancy and lactation, remodeling a relatively simple ductal structure into an extensive network of milk secreting alveoli. Estradiol, through activation of estrogen receptor (ER), plays an essential role in the early expansion of the mammary epithelium during pregnancy, but has little role during lactation when circulating levels are low. Yet, ER is present in the epithelium during lactation and exposure to estrogenic endocrine disrupting chemicals (EDCs) could disrupt the lactational capability of the mammary gland. To understand the effects of ER agonists during lactation, we exposed CD-1 mice to ethinyl estradiol [20 μg/kg] from lactation day 1 (LD1) until weaning at LD21. To assess changes in lactational output, pup weight gain was assessed throughout the lactation period. Both maternal weight gain and maternal behavior were observed as well. Maternal mammary glands were collected and assessed for changes in histomorphology and molecular indicators of differentiation and cell death. We observed that EE2 exposure restricted weight growth in dams, increased time nursing on the nest and reduced other maternal activities. EE2 exposed pups had restricted growth and development. At weaning, EE2 exposed dams had less epithelial complexity than VEH controls despite no changes in alveolar structure. Molecular analysis of the mammary gland at weaning indicated that EE2 reduced epithelial pSTAT3 expression, an early indicator of cell degradation, without altering differentiation markers or apoptosis. These findings indicate that EE2 exposure reduces epithelial expansion in lactation prior to weaning, resulting in restricted growth and development in pups.

PMID:40324638 | DOI:10.1016/j.reprotox.2025.108931

J Biomol Struct Dyn. 2025 May 4:1-14. doi: 10.1080/07391102.2025.2498078. Online ahead of print.

ABSTRACT

Lignin peroxidases (LiP; EC 1.11.1.14) are important oxidative enzymes involved in lignin biodegradation, a key constituent of plant cell walls. Despite their environmental and industrial potential, fungal LiPs are difficult to express and purify. Bjerkandera adusta is a white-rot fungus that secretes LiPs, the three-dimensional structure of which remains unknown. In this study, two LiPs from B. adusta were subjected to various bioinformatics tools to determine their physio-chemical, structural, and functional properties. Their 3D structure was modeled and molecular dynamic simulations were performed to assess their binding to endocrine disrupting chemicals (EDCs). Moreover, molecular docking analysis revealed that among the model lignin compounds, the dimer guaiacyl 4-O-5 guaiacyl exhibited the lowest binding energy with the EDC ligands, estrone (E1) and bisphenol A showing the strongest binding affinity for LiP 588479560 and LiP 444058, respectively. Molecular dynamics simulations further confirmed the stability of these complexes, with bisphenol A exhibiting particularly high stability as indicated by its low RMSD (≤2 Å) and favorable RoG values, reflecting a strong fit within the enzyme's active site. Additionally, the binding free energy calculations showed the substrate dimer had the most favorable binding energy, driven primarily by Van der Waals and lipophilic interactions, suggesting its intrinsic compatibility with B. adusta LiPs. This in silico characterization advances the understanding of LiP structure-function relationships and bioremediation potential. B. adusta LiPs demonstrate promising capacity to target persistent EDCs, offering solutions for environmental pollution mitigation.

PMID:40319496 | DOI:10.1080/07391102.2025.2498078

J Hazard Mater. 2025 Apr 29;494:138433. doi: 10.1016/j.jhazmat.2025.138433. Online ahead of print.

ABSTRACT

Improving our understanding of how environmental pollution affects aquatic life requires a holistic approach. This study provides new insights into the intrinsic biological defence of brown trout (Salmo trutta m. fario L.) against chemical pollution in a stream with a low-dilution factor, a common scenario in headwaters globally. Fish restocked downstream of a sewage treatment plant (STP) were compared with a control group upstream of STP. Trout tissues were sampled after 6, 14, and 24 weeks and subjected to biochemical and histological analyses. Passive samplers were deployed at both stream stretches to reflect concentrations of freely dissolved organic micropollutants and their bioactivity effects using in vitro reporter gene bioassays. Chemical analysis downstream revealed elevated concentrations of micropollutants compared to upstream. In vitro bioassays detected increased androgenicity, estrogenicity, and transthyretin-binding inhibition. Antioxidant and biotransformation enzyme activities in fish indicated gradual acclimation to pollution despite minor histopathological changes. Elevated vitellogenin and 17β-estradiol in males suggested pollution-induced endocrine disruption. Although the results obtained from water chemical profiling and bioassays have a causal relationship to fish health, trout's molecular defence system allowed gradual acclimation to pollution, mitigating broader ecological impacts. The study advanced the knowledge of how fish cope with wastewater-borne micropollutants in aquatic environments.

PMID:40319851 | DOI:10.1016/j.jhazmat.2025.138433

Stem Cell Res Ther. 2025 May 4;16(1):225. doi: 10.1186/s13287-025-04314-5.

ABSTRACT

BACKGROUND: Thioredoxin-interacting protein (TXNIP) plays a role in regulating endoplasmic reticulum (ER) and oxidative stress, which disrupt glucose homeostasis in diabetes. However, the impact of TXNIP deficiency on the differentiation and functionality of human stem cell-derived somatic metabolic cells remains unclear.

METHODS: We used CRISPR-Cas12a genome editing to generate TXNIP-deficient (TXNIP^-/-) H1 human embryonic stem cells (H1-hESCs). These cells were differentiated into hepatocyte-like cells (HLCs) and stem-cell-derived insulin-producing islets (SC-islets). The maturation and functionality TXNIP^-/- and TXNIP^+/+ SC-islets were assessed by implantation under the kidney capsule of male or female NOD-SCID mice.

RESULTS: TXNIP deficiency significantly increased H1-hESC proliferation without affecting pluripotency, viability, or differentiation potential into HLCs and SC-islets. Bulk RNA-sequencing of thapsigargin-treated TXNIP^-/- and TXNIP^+/+ hESCs revealed differential expression of stress-responsive genes, with enriched apoptosis-related pathways in TXNIP^+/+ cells, but minimal transcriptional changes specific to TXNIP deficiency. In HLCs, TXNIP deletion reduced albumin secretion and insulin signalling, as indicated by decreased AKT phosphorylation, while showing no differences in glycolytic activity or lipid metabolism markers. Under thapsigargin-induced ER stress, TXNIP^-/- HLCs exhibited transiently reduced eIF2α phosphorylation and lower BiP expression, suggesting compromised adaptive responses to prolonged stress. SC-islets derived from TXNIP^-/- hESCs showed comparable viability, endocrine cell composition, and cytokine responses to TXNIP^+/+ islets. Following IFNα or IFNγ treatment, STAT1 phosphorylation was increased in TXNIP^-/- SC-islets, indicating that IFN signalling remained intact despite TXNIP deficiency. Upon implantation into NOD-SCID mice, both TXNIP^-/- and TXNIP^+/+ SC-islets produced human C-peptide and responded to glucose stimulation. However, TXNIP^-/- SC-islets did not demonstrate enhanced glycaemic control or glucose-stimulated insulin secretion compared to controls.

CONCLUSIONS: Our study demonstrates that TXNIP deficiency does not improve the differentiation or functionality of HLCs and SC-islets. We present the generation and characterisation of TXNIP^-/- and TXNIP^+/+ H1-hESCs, HLCs, and SC-islets as valuable models for future studies on the role of TXNIP in metabolic cell biology.

PMID:40320524 | PMC:PMC12051322 | DOI:10.1186/s13287-025-04314-5

Food Chem Toxicol. 2025 May 1;202:115504. doi: 10.1016/j.fct.2025.115504. Online ahead of print.

ABSTRACT

Gut hormones secreted by enteroendocrine cells play a critical role in maintaining glucose homeostasis. However, the adverse endocrine effects related to glucose homeostasis caused by food additives are not well understood. This work aims to investigate the effects of titanium dioxide nanoparticles (TiO₂ NPs) in comparison to titanium dioxide microparticles (TiO₂ MPs) on glucose homeostasis, with a specific focus on the enteroendocrine cells and gut hormones. Our research found that exposure to 1 % (w/w) TiO₂ NPs, unlike TiO₂ MPs, resulted in elevated blood glucose levels and impaired glucose tolerance in mice. Notably, 1 % (w/w) TiO₂ NPs significantly influenced the differentiation of the intestinal epithelium while not causing any notable histological changes or affecting cell proliferation in the mouse ileum. Furthermore, the levels of gut hormones, including glucagon-like peptide-1 (GLP-1), peptide YY (PYY) and cholecystokinin (CCK), released from mouse ileum tissues were also significantly reduced following exposure to 1 % (w/w) TiO₂ NPs. Using the intestinal organoid model, we also discovered that 20 μg/mL TiO₂ NPs impaired enteroendocrine cell differentiation, reduced basal GLP-1 secretion levels, and disrupted the GLP-1 secretion response to nutrient stimuli. Our research highlights the detrimental effects of TiO₂ NPs as potential intestinal endocrine disruptor and underscores the need to optimize their particle size for safe use in the food industry.

PMID:40318823 | DOI:10.1016/j.fct.2025.115504

Food Chem Toxicol. 2025 May 1;202:115501. doi: 10.1016/j.fct.2025.115501. Online ahead of print.

ABSTRACT

The prevalence of nonalcoholic fatty liver disease (NAFLD), exacerbated by endocrine disruptors like phthalate-plasticizers, underscores the need to understand their impact on hepatic lipid metabolism. Although the suppression of hepatic macrophage M2 polarization is known to contribute to diethylhexyl phthalate (DEHP)-induced hepatic lipid accumulation, the role of intracellular metabolism in macrophages remains unclear. Here, we investigated the role of arachidonic acid metabolism-a key regulator of M2 macrophage polarization-and its metabolite prostaglandin E2 (PGE2) in DEHP-induced hepatic lipid disorders. DEHP exposure disrupted lipid metabolism and reduced hepatic macrophages. Genomic and metabolomic analyses of mice revealed a strong correlation between decreased hepatic M2 macrophages and perturbed arachidonic acid metabolism. Elevating the PGE2 level attenuated the inhibition of M2 macrophages caused by DEHP or its metabolite mono- (2-ethylhexyl) phthalate (MEHP) both in vitro and in vivo. Additionally, PGE2-induced M2 macrophages alleviated DEHP/MEHP-induced lipid metabolism disorders. In summary, arachidonic acid metabolism and PGE2 are critical metabolic regulators in DEHP-induced lipid metabolism disorders. This study identifies a novel metabolic target related to macrophage polarization in phthalates toxicity and provides a foundation for therapeutic strategies against endocrine disruptor-associated NAFLD.

PMID:40318824 | DOI:10.1016/j.fct.2025.115501