Reproductive toxicology最新文献

{"title":"Identification of key genes involved in phthalate-induced male erectile dysfunction: Insights from network toxicology and bioinformatics analyses.","authors":"Yuqi Li, Juan Wang, Zhiyu Liu, Xinyao Zhu, Qilong Wu, Chunyang Meng, Qingfu Deng","doi":"10.1016/j.reprotox.2025.109026","DOIUrl":"10.1016/j.reprotox.2025.109026","url":null,"abstract":"<p><strong>Background: </strong>In recent years, phthalate plasticizers have been increasingly linked to various male reproductive health issues. However, their relationship with erectile dysfunction (ED) remains insufficiently studied. This study aims to elucidate the molecular mechanisms by which phthalate plasticizers contribute to ED.</p><p><strong>Methods: </strong>Using a network toxicology approach, we predicted potential molecular targets of three common phthalates-DEHP, DIBP, and DMP-associated with ED through multiple online databases. Next, we integrated transcriptomic datasets from three established ED rat models (diabetic, neurogenic, and hypertensive) to identify more robust and representative candidate genes. Subsequently, LASSO and SVM-RFE machine learning algorithms were employed to screen for key phthalate related ED genes. Molecular docking was then conducted to validate the binding affinity between phthalates and these candidate targets.</p><p><strong>Results: </strong>Network toxicology analysis identified 101 genes potentially linking phthalates to ED. Enrichment analyses revealed that these genes are primarily involved in endothelial dysfunction, oxidative stress, and cell growth regulation. From the integrated ED transcriptomic dataset, 1002 differentially expressed genes were identified, among which 12 overlapped with the phthalate-ED associated genes. These overlapping genes were closely related to neurodegenerative diseases and metabolic disorders. LASSO and SVM-RFE models further narrowed the list to four key genes: CDKN1B, IDH1, CASR, and PRNP.</p><p><strong>Conclusion: </strong>The four key genes-CDKN1B, IDH1, CASR, and PRNP-appear to play critical roles in phthalate-induced ED. These genes are potentially involved in mechanisms such as oxidative stress dysregulation, neural injury, and endocrine disorders. Our findings provide important theoretical insights into the pathogenesis and prevention of environmentally induced ED.</p>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":" ","pages":"109026"},"PeriodicalIF":2.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single and combined brominated flame retardants exposures are associated with sex steroid hormones in US adults: NHANES 2013-2016 analysis.","authors":"Guan Cheng, Jiahui Wen, Feng Zhang, Rui Qu, Zhimin Deng, Fangfang Dai, Yanfei Xiao, Mengyang Dai, Tailang Yin, Jie Yan, Yan Zhang","doi":"10.1016/j.reprotox.2025.109023","DOIUrl":"10.1016/j.reprotox.2025.109023","url":null,"abstract":"<p><strong>Background: </strong>Brominated flame retardants (BFRs) are endocrine-disrupting contaminants; however, the impact of BFR mixtures on sex steroid hormone levels in adults remains unclear.</p><p><strong>Methods: </strong>This study included 2513 male and female adults from the 2013-2016 National Health and Nutrition Examination Survey (NHANES). Weighted linear regression was employed to examine the associations between individual BFR exposures and total testosterone(TT), estradiol(E2), sex hormone binding globulin (SHBG), free androgen index (FAI), and TT/E2. The generalized additive model (GAM) was used to explore the nonlinear associations between BFRs and sex steroid hormones. Additionally, weighted quantile sum (WQS) regression and Quantile G-computation (QGC) were applied to evaluate the overall effects of BFRs mixtures on these five sex hormone biomarkers and to identify key contributing chemicals. We also explored potential effect modifications by age, BMI and educational level.</p><p><strong>Result: </strong>The weighted linear regression results indicated that, after adjusting for covariates, PBDE209 was significantly negatively associated with SHBG in males (β = -8.495, 95 % CI: -15.915, -1.073), while PBB153 and PBDE85 were negatively associated with female TT/E2 (β = -0.718, 95 % CI: -1.362, -0.075) and E2 (β = -2.910, 95 % CI: -5.126, -0.693), respectively. The Generalized Additive Model (GAM) revealed nonlinear associations between certain BFRs and TT, E2, FAI, and TT/E2 in both males and females. WQS regression analysis showed a significant negative association between the WQS index and male SHBG (β = -1.919, 95 % CI: -3.706, -0.133), which was consistent with the results from the weighted linear regression. However, no significant associations were observed between mixed BFR exposure and female sex hormone levels. Further confirmation of the WQS regression findings was provided by QGC analysis. Notably, PBDE209 was identified as the primary BFR influencing SHBG levels.</p><p><strong>Conclusion: </strong>Exposure to mixed BFRs significantly affects SHBG levels in adult males, while no significant impact on sex steroid hormone levels was observed in adult females. Further studies are required to evaluate the potential long-term health consequences.</p>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":" ","pages":"109023"},"PeriodicalIF":2.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microplastics and gynecological tumors: An emerging environmental health concern.","authors":"Yuling Hu, Zhihui Song, Jingwen Li, Feiyi Yang, Ling Li","doi":"10.1016/j.reprotox.2025.109018","DOIUrl":"10.1016/j.reprotox.2025.109018","url":null,"abstract":"<p><p>The pervasive environmental contamination by microplastics (MPs) has emerged as a significant threat to human health, with mounting evidence linking exposure to gynecological tumors. This comprehensive review synthesizes current scientific evidence by examining the established risks of chemical additives, exploring the carcinogenic mechanisms of the particles themselves, and highlighting the recent direct detection of MPs in human gynecological tissues. Evidence for this association is multi-faceted: plastic additives such as phthalates and bisphenol A (BPA) are epidemiologically linked to increased cancer risk, while the MP particles themselves are shown to induce pro-carcinogenic responses including oxidative stress, chronic inflammation, and epigenetic changes. Critically, recent studies now confirm the physical presence of MPs within human gynecological tumor tissues, often at higher concentrations than in adjacent normal tissue, strengthening the clinical relevance of these findings. The convergence of chemical, mechanistic, and clinical evidence establishes a compelling case for MP exposure as an emerging risk factor for gynecological malignancies. The findings underscore an urgent need for further research, standardized detection methodologies, and public health strategies to mitigate this environmental threat.</p>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":" ","pages":"109018"},"PeriodicalIF":2.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144761143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship of parental phthalate exposure with fetal growth and placental development at birth.","authors":"Hye Jin Chang, Yoon Hee Cho, Yeong Sook Yoon, Younglim Kho, Je Yeon Lee, Dong Won Hwang, Jung Yeol Han, Jisun Lee, Young Ah Kim","doi":"10.1016/j.reprotox.2025.109025","DOIUrl":"10.1016/j.reprotox.2025.109025","url":null,"abstract":"<p><strong>Background: </strong>Prenatal exposure to phthalates is reported to influence fetal growth and may lead to lasting adverse effects on infants and their future development; yet, the results remain inconclusive.</p><p><strong>Objective: </strong>This study utilized a birth cohort of 73 pregnant women-newborn pairs, including biological fathers (73 triads), to investigate the relationship between parental phthalate exposure during pregnancy and birth outcomes in newborns.</p><p><strong>Methods: </strong>Demographic, behavioral, and clinical information, along with urine samples from both parents, were collected prior to delivery. Sixteen phthalate metabolites were quantified in urine samples.</p><p><strong>Results: </strong>Significant correlations were observed between six phthalate metabolites (MEP, MiBP, MnBP, MBzP, MEHP, and 5cx-MEPP) in maternal urine and paternal levels. Maternal MBzP was positively associated with boys' birth weight, whereas maternal 2cx-MMHP was negatively associated with girls' birth weight. The ponderal index of boys was negatively related to maternal MBzP and MMP, but positively associated with ∑MEHP-3 and ∑MEHP-5 after adjusting for confounding variables. Among paternal phthalates, MBzP showed a negative association with boys' ponderal index, whereas MEP showed a positive association. Maternal MEOHP, ∑MEHP-3, and ∑MEHP-5 were positively associated with boys' placenta weight, while MEOHP, MEHHP, 5cx-MEPP, ∑MEHP-3, and ∑MEHP-5 were negatively associated with girls' placenta weight.</p><p><strong>Conclusions: </strong>Our findings suggest that parental exposure to phthalates at birth may adversely affect fetal growth and placental development in neonates. However, further studies with larger sample sizes and datasets are necessary.</p>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":" ","pages":"109025"},"PeriodicalIF":2.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silibinin attenuates 3-nitropropionic acid-induced ovarian toxicity by alleviating oxidative stress and granulosa cell apoptosis.","authors":"Yedan Gai, Wenhao Wu, Haoyu Wang, Yuqing Li, Changbo Li, Yingyu Wang, Yaolu Zhao, Jianmin Hu, Xinhong Luan","doi":"10.1016/j.reprotox.2025.109027","DOIUrl":"10.1016/j.reprotox.2025.109027","url":null,"abstract":"<p><p>3-Nitropropionic acid (3-NP), a mycotoxin present in various plants and fungi, poses significant reproductive health risks to animals and humans through food chains contamination. This study aimed to explore the protective effects and mechanisms of silibinin, a bioactive flavonoid derived from the herbal plant Silybum marianum, against 3-NP-induced reproductive toxicity. Our findings demonstrated that silibinin treatment significantly alleviated 3-NP-induced ovarian follicular atresia and preserved ovarian histoarchitecture. Furthermore, it attenuated oxidative stress induced by 3-NP. Molecular analyses through qPCR and Western blot revealed that silibinin upregulated Bax and Caspase-3 expressions while downregulating Bcl-2 expression in the ovaries compared to the 3-NP group. Immunohistochemistry analysis of CASPASE-3 demonstrated that silibinin significantly inhibited 3-NP-induced apoptosis, predominantly in granulosa cells. Additionally, Western blot analyses showed that silibinin suppressed 3-NP-induced activation of JNK and ERK phosphorylation, downregulated KEAP1 expression, and upregulated NRF2 nuclear translocation in the ovary. Overall, our results indicate that silibinin effectively alleviated 3-NP-induced ovarian oxidative damage by modulating the JNK/ERK signaling pathways and activating the KEAP1/NRF2 signaling pathway. These findings suggest that silibinin may have potential therapeutic application for mitigating 3-NP-induced reproductive toxicity in animal husbandry and the veterinary industry.</p>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":" ","pages":"109027"},"PeriodicalIF":2.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Mono- (2-ethylhexyl) phthalate and Phthalic Acid Monobenzyl Ester on endometriosis using network toxicology, machine learning and molecular docking techniques.","authors":"Qi Wu, Yu Meng Sun, Qiong Hua Liu, Xing Yue Zhao, Ze Li, Li Xu, Wei Shi","doi":"10.1016/j.reprotox.2025.109024","DOIUrl":"10.1016/j.reprotox.2025.109024","url":null,"abstract":"<p><p>Phthalate metabolites Mono- (2-ethylhexyl) phthalate(MEHP) and Phthalic Acid Monobenzyl Ester (MBZP) are widely present in the environment, can interfere with the endocrine system and accumulate in human tissues, and are closely related to the occurrence and development of endometriosis. In this study, by integrating multiple databases such as ChEMBL and STITCH, 503 human target genes of the two metabolites were screened out. After intersection with 1735 genes related to endometriosis, a core gene set of 50 was obtained. GO and KEGG enrichment analyses revealed that these genes were mainly involved in pathways such as arachidonic acid metabolism, IL-17 signaling pathway, cell burial, and complement-coagulation cascade reaction, and were involved in the processes of survival, migration, and fibrotic remodeling of ectopic endometrial cells driven by oxidative stress. Through the construction of PPI networks and the validation of machine learning models, ACE, MMP2, PPARG and SERPINE1 were identified as key hub proteins.The diagnostic ability AUC of each single gene reaches 0.80.Molecular docking experiments confirmed that MEHP and MBZP have high affinity (ΔG - 8.5 to - 6.3 kcal/mol) for the above-mentioned proteins, providing atomic-level evidence for their molecular regulatory mechanisms. This study systematically elucidated the multi-level mechanisms of endometriosis caused by phthalate exposure and proposed a precise diagnostic strategy based on core genes, providing new ideas for the prevention and targeted treatment of diseases related to environmental pollutants.</p>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":" ","pages":"109024"},"PeriodicalIF":2.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144795258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gestational exposure to poly/perfluoroalkyl substances and risk of congenital structural malformations: A nested case-control study.","authors":"Yanhong Wu, Yilin Lv, Shuang Ran, Wanqin Xie, Haiyan Zhou, Ziwei Zhang, Huamin Yuan, Xingli Li","doi":"10.1016/j.reprotox.2025.109074","DOIUrl":"https://doi.org/10.1016/j.reprotox.2025.109074","url":null,"abstract":"<p><p>Congenital structural malformations (CSM) have become a significant public health and social issue, affecting the health status of children and the level of population quality. Emerging research increasingly suggests that environmental pollutants may contribute to the development of CSM. However, current epidemiologic evidence on the effects of per- and polyfluoroalkyl substances (PFAS) on CSM is limited and restrictive. A nested case-control study examined how maternal exposure to PFAS during pregnancy affects the risk of CSM. Logistic regression and Bayesian kernel machine regression (BKMR) were used to assess the effects of single PFAS and PFAS mixture exposure on CSM. Perfluorodecanoic acid (PDA) showed a strong positive association with CSM in the logistic regression model (Adjusted OR: 4.79, 95% CI: 1.55 ~ 18.52). The BKMR analysis indicated an increased risk of CSM as PFAS mixture levels rose above the 55th percentile. Individual PFAS were ranked by posterior inclusion probabilities (PIPs), with PDA (PIP = 1.00), perfluorooctanoic acid (PFOA) (PIP = 1.00), potassium 9-chlorohexadecafluoro-3-oxanonane-1-sulfonate (9Cl_PF3ONS) (PIP = 0.88), and perfluorononanoic acid (PFNA) (PIP = 0.82) contributing most to the mixture's effect on CSM. No significant interactions were observed between PFAS mixtures when other exposures were held constant at the 50th percentile. In conclusion, we found that prenatal exposure to PDA and PFAS mixtures was significantly linked to a heightened risk of CSM, with PDA, PFOA, 9Cl_PF3ONS, and PFNA being significant contributors to the mixture effect. In addition, our study did not identify any previous interactions of PFAS.</p>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":" ","pages":"109074"},"PeriodicalIF":2.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring potential mechanisms of artificial sweeteners in polycystic ovary syndrome through network toxicology and molecular docking.","authors":"Huan He, Yinjuan Lyu, Manquan Fu, Xiaocui Jiang, Jianmin Liu, Min Xiao","doi":"10.1016/j.reprotox.2025.109073","DOIUrl":"https://doi.org/10.1016/j.reprotox.2025.109073","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder increasingly prevalent among women of reproductive age. Artificial sweeteners, commonly used as sugar substitutes, are now under scrutiny for their potential disruption of metabolic and hormonal equilibrium. This investigation delves into the molecular mechanisms through which seven artificial sweeteners (aspartame, saccharin, sucralose, acesulfame-K, sodium cyclamate, neotame, and alitame) may impact the development of PCOS. By employing network toxicology and molecular docking methodologies, we identified 85 common targets shared between genes associated with sweeteners and those linked to PCOS. Enrichment analyses using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways unveiled connections to inflammation, insulin resistance, and steroid biosynthesis, particularly implicating pathways such as TNF signaling, AGE-RAGE signaling, and the AMPK pathway. Notably, key targets like TNF, STAT3, and IFNG displayed high binding affinities with artificial sweeteners in molecular docking simulations. These results suggest a potential role for artificial sweeteners in exacerbating PCOS progression through inflammatory and metabolic pathways, underscoring the need for further experimental validation.</p>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":" ","pages":"109073"},"PeriodicalIF":2.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of bisphenol A exposure with in vitro fertilization outcomes: A meta-analysis and systematic review","authors":"Mengke Yuan ,&nbsp;Jie Chai ,&nbsp;Jingyan Song ,&nbsp;Xinyan Wang ,&nbsp;Zhengao Sun ,&nbsp;Xianling Cao","doi":"10.1016/j.reprotox.2025.109071","DOIUrl":"10.1016/j.reprotox.2025.109071","url":null,"abstract":"<div><h3>Background</h3><div>The impact of bisphenol A (BPA) on in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) outcomes remains unclear.</div></div><div><h3>Methods</h3><div>This systematic review and meta-analysis evaluated studies from Pubmed, Web of Science, EMBASE, and Cochrane Library (up to April 19, 2024), analyzing data using regression coefficient (β) and their 95 % confidence intervals (CIs).</div></div><div><h3>Results</h3><div>A total of 478 references were identified and 14 studies with different IVF/ICSI outcomes were included in the final meta-analysis. The included studies reported that the median or geometric mean (GM) of specific gravity (SG) or creatinine (Cr)-adjusted maternal urinary BPA ranged from 0.063 to 2.61 ng/ml. The meta-analysis results indicated a significant negative correlation between urinary, serum, follicular fluid (FF), and semen BPA exposure and several key IVF/ICSI outcomes, particularly in terms of normal fertilization rates (β: −0.05; 95 % CI: −0.07, −0.03) and the number of high-quality embryos (β: −0.05; 95 % CI: −0.09, −0.01). In the subgroup analysis based on BPA exposure level, higher BPA exposure was significantly associated with decreased normal fertilization rate in IVF/ICSI, particularly in populations with BPA median or GM concentrations above 1.55 ng/ml (β: −0.19; 95 % CI: −0.27, −0.11). However, no significant association was observed between BPA exposure and clinical pregnancy rates, blastocyst formation, or implantation success rates, which may be attributed to the limited number of studies and variability in study design and populations.</div></div><div><h3>Conclusion</h3><div>This meta-analysis suggests that BPA, a common environmental pollutant, may reduce reproductive success during IVF/ICSI by disrupting endocrine function and compromising gamete quality and early embryo development. However, due to study limitations, further research is needed to confirm our findings and explore the mechanisms underlying reproductive toxicity.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"138 ","pages":"Article 109071"},"PeriodicalIF":2.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Involvement of autophagy and mitophagy modulation in the protective effect of melatonin against BPS-induced ovarian toxicity","authors":"Lina Chouchene,&nbsp;Kaouthar Kessabi,&nbsp;Lobna Lajmi,&nbsp;Imed Messaoudi","doi":"10.1016/j.reprotox.2025.109072","DOIUrl":"10.1016/j.reprotox.2025.109072","url":null,"abstract":"<div><div>Plastics pose a global health risk due to their detrimental effects, with bisphenol S (BPS) being a prominent plasticizer of concern. In this study, we aimed to investigate the effects of BPS exposure on ovarian function in Wistar rats and assess the protective potential of melatonin (MLT), with the goal of elucidating some of the underlying biochemical and molecular mechanisms involved. We first assessed changes in weight parameters and oxidative stress markers, including antioxidant enzymes (SOD and CAT), PSH, and MDA levels. Then, we investigated ovarian function parameters, namely those related to the estrous cycle, ovarian histology, folliculogenesis, and the molecular expression of markers associated with autophagy (LC3, P62, ATG5) and mitophagy (PINK1, PARKIN) processes. Our findings indicate that BPS induces oxidative stress, with increased CAT activity and decreased SOD activity, along with elevated PSH levels, without any effect on lipid peroxidation. Significant ovarian toxicity is also evident, manifested by a decrease in ovarian weight and anomalies related to the estrous cycle, such as irregularities and disruptions in the total duration and the different estrous phases, along with histological alterations in ovarian tissue that result in variations in the number of follicles at different maturation stages. Furthermore, BPS exposure induces an overexpression of LC3, ATG5, P62, PINK1 and PARKIN markers. Conversely, MLT supplementation significantly mitigated these effects, mainly through its ability to improve oxidative status and to modulate autophagy and mitophagy processes, resulting in the restoration of ovarian function parameters and highlighting its protective role against BPS-induced ovarian toxicity.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"138 ","pages":"Article 109072"},"PeriodicalIF":2.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}