Reproductive toxicology最新文献

{"title":"Allicin attenuates doxorubicin-induced testicular and systemic toxicity in rats via antioxidant and anti-apoptotic mechanisms.","authors":"Mardin Omer Mohammed, Faraidoon Abdulstar Muhamad, Hiewa Othman Dyary","doi":"10.1016/j.reprotox.2025.109082","DOIUrl":"https://doi.org/10.1016/j.reprotox.2025.109082","url":null,"abstract":"<p><p>The clinical use of doxorubicin (DOX) is limited by toxicity in rapidly dividing tissues, notably the testes. This study evaluated allicin as a protective agent against DOX‑induced reproductive toxicity in male rats. Thirty-six male Sprague Dawley rats were randomly divided into six groups (n = 6): Group 1 received saline; Group 2 received DOX (a cumulative dose of 7.5mg/kg, i.p. on days 8, 11, and 14); Group 3 received allicin alone (dissolved in corn oil, 20mg/kg/day, orally for 14 days); Group 4 received DOX + allicin (10mg/kg/day); Group 5 received DOX + allicin (20mg/kg/day); and Group 6 received corn oil as the vehicle control. DOX treatment induced severe oxidative stress (OS), as evidenced by a 6.5-fold increase in malondialdehyde (MDA) and an 83% decrease in superoxide dismutase (SOD) activity, indicating lipid peroxidation and impaired antioxidant defence. Allicin coadministration reduced MDA by 47% and recovered SOD activity to 73% of the control level. Furthermore, the TUNEL assay revealed a 4.6-fold increase in apoptotic index in DOX-treated rats, which allicin significantly attenuated dose-dependently. DOX upregulated MMP-9 (3.1-fold) and downregulated Cx43 and mTOR to 15% and 18% of the control levels, respectively, while allicin normalized these levels. Reproductive outcomes were compromised by DOX, with a 38% decline in sperm count, a 65% reduction in viability, a 93% drop in testosterone, and a 51% increase in morphological abnormalities; allicin improved these metrics by up to 60%. Hematologically, DOX induced pancytopenia, which was partially reversed by allicin, resulting in an increase in leukocytes, erythrocytes, and platelets. In summary, allicin ameliorated DOX‑induced testicular and systemic toxicity through antioxidant, anti‑apoptotic, and gene‑regulatory mechanisms.</p>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":" ","pages":"109082"},"PeriodicalIF":2.8,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145337480","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 exposure to 17 endocrine disrupting chemicals on sex steroid hormone levels in 12- to 19-year-old males in the United States","authors":"Adila Adili,&nbsp;Haoran Liu,&nbsp;Hui Tian,&nbsp;Yuanyuan Ji,&nbsp;Xiaofang Han","doi":"10.1016/j.reprotox.2025.109078","DOIUrl":"10.1016/j.reprotox.2025.109078","url":null,"abstract":"<div><div>Endocrine disrupting chemicals are widespread in the environment and can interfere with reproductive hormone regulation, but their effects during adolescence are not yet clear. This study investigated the associations between exposure to multiple endocrine disrupting chemicals and sex steroid hormone levels in adolescent males. Data were obtained from the National Health and Nutrition Examination Survey 2013–2016, including males aged 12–19 years. Urinary concentrations of 17 endocrine disrupting chemicals, including phthalates, phenols, and parabens, were analyzed in relation to serum sex hormones. Associations were examined using linear regression, quantile g-computation, and Bayesian kernel machine regression to capture both single and mixture exposures. Linear regression identified inverse associations of mono-(3-carboxypropyl) phthalate with total testosterone, estradiol, free androgen index, free testosterone, and bioavailable testosterone. Mono-(2-ethyl-5-hydroxyhexyl) phthalate was inversely associated with estradiol, free androgen index, free testosterone, and bioavailable testosterone, but positively associated with sex hormone-binding globulin. Quantile g-computation confirmed these relationships, while Bayesian kernel machine regression demonstrated that combined exposure to 17 endocrine disrupting chemicals collectively reduced total testosterone, estradiol, free androgen index, free testosterone, and bioavailable testosterone, while increasing sex hormone-binding globulin. These findings reveal a consistent pattern of elevated binding globulin levels accompanied by decreased bioactive sex hormones. In conclusion, exposure to endocrine disrupting chemicals, both individually and as mixtures, is associated with altered sex steroid hormone levels in adolescent males. These results underscore the importance of environmental regulation to limit exposure during this critical developmental stage and highlight the potential role of chemical mixtures in adolescent reproductive health.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"138 ","pages":"Article 109078"},"PeriodicalIF":2.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308406","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 individual and combined exposure to polycyclic aromatic hydrocarbon (PAH) and phthalate (PAE) metabolites with maternal estradiol levels in early pregnancy: A cross-sectional study","authors":"Lin Tao ,&nbsp;Jing Yang ,&nbsp;Zhongmei Hu ,&nbsp;Dengqing Liao ,&nbsp;Shimin Xiong ,&nbsp;LuLu Dai ,&nbsp;Yuan-zhong Zhou ,&nbsp;Xubo Shen","doi":"10.1016/j.reprotox.2025.109081","DOIUrl":"10.1016/j.reprotox.2025.109081","url":null,"abstract":"<div><div>Polycyclic aromatic hydrocarbons (PAHs) and phthalates (PAEs) exert endocrine-disrupting effects; however, research investigating the relationship between co-exposure to these two classes of pollutants and sex hormone levels in pregnant women remains limited. To address this gap, we enrolled 454 women in early pregnancy from the Zunyi Birth Cohort (ZBC) and used linear mixed-effects models (LMM), Bayesian kernel machine regression (BKMR), and restricted cubic spline (RCS) models to examine associations between early-pregnancy both individual and combined exposur to PAHs and PAEs and maternal estradiol levels. LMM results revealed no significant associations between PAH metabolites and estradiol, but significant associations between PAE metabolites and estradiol—primarily driven by monoisobutyl phthalate (MIBP) and monobutyl phthalate (MBP), with corresponding β values (95 % confidence intervals [CIs]) of −534.77 (-761.17, −308.37) and 473.19 (233.80, 712.58), respectively. BKMR analyses showed that exposure to PAH metabolites alone was negatively associated with estradiol, primarily involving 4-hydroxyphenanthrene (4-OHPH) and 1-hydroxypyrene (1-OHPYR). Exposure to PAE metabolites alone was also negatively associated with estradiol, driven mainly by monoethyl phthalate (MEP), MIBP, and MBP. Concurrent exposure to PAE and PAH metabolites was negatively associated with estradiol, with key contributors including 2-hydroxyfluorene (2-OHFLU), MiBP, MBP, mono(2-ethylhexyl) phthalate (MEHP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP). RCS results demonstrated an inverted U-shaped relationship between 2-OHFLU and estradiol (<em>F</em>=2.8, <em>P</em> = 0.019), a non-linear negative association between MIBP and estradiol (<em>F</em>=3.3, <em>P</em> = 0.002), and an inverted U-shaped relationship between MEOHP and estradiol (<em>F</em>=4.4, <em>P</em> = 0.005). Collectively, these findings indicate that both individual and combined exposure to PAHs and PAEs in early pregnancy is associated with estradiol levels in pregnant women, with evidence of exposure-response relationships. Reducing exposure to PAH and PAE metabolites in early pregnancy is recommended to further safeguard maternal and fetal health.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"138 ","pages":"Article 109081"},"PeriodicalIF":2.8,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286864","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":"From exposure to outcomes: How air pollutants impact maternal and foetal health","authors":"Garvita Parikh,&nbsp;Bhoomika Patel","doi":"10.1016/j.reprotox.2025.109080","DOIUrl":"10.1016/j.reprotox.2025.109080","url":null,"abstract":"<div><div>Air pollution is a leading environmental risk factor, contributing significantly to respiratory illnesses, cardiovascular diseases, and other chronic conditions; ultimately increasing the global burden of ailments. While the harmful effects of air pollutants on the respiratory and cardiovascular systems are well-known, concerns over their impact on pregnancy outcomes are rising. Pregnant women and their developing fetuses are particularly more susceptible to the harmful effects of air pollutants, which can penetrate the placental barrier and lead to a wide range of negative consequences, such as preeclampsia, premature rupture of membranes, gestational diabetes, and placenta previa. These consequences concurrently lead to adversarial birth outcomes like congenital abnormalities, developmental delays, preterm birth, etc. This review elucidates the link between maternal exposure to air pollutants and the subsequent occurrence of adverse pregnancy and birth outcomes. It also explores the utility of various biomarkers, including inflammatory markers, oxidative stress markers, and molecular markers, used to assess the presence of air pollutants and their impact on pregnancy and birth outcomes. Furthermore, through assimilating these insights, this review emphasizes the crucial need for targeted interventions and policies to mitigate the air pollutants deadly effect on sensitive and vulnerable groups.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"138 ","pages":"Article 109080"},"PeriodicalIF":2.8,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286837","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":"In utero exposure to acetaminophen and childhood attention deficit hyperactivity disorder: An ongoing controversy","authors":"Per Damkier,&nbsp;Erika B. Gram","doi":"10.1016/j.reprotox.2025.109076","DOIUrl":"10.1016/j.reprotox.2025.109076","url":null,"abstract":"<div><div>Attention Deficit Hyperactivity Disorder (ADHD) in children as related to maternal use of acetaminophen (paracetamol, APAP) remains an ongoing controversy. In a recent paper in Nature Mental Health, Baker et al. reports on ADHD in children as related to maternal use of acetaminophen APAP in pregnancy. We discuss the methodological strengths and limitations and the extent to which this paper informs clinical practice.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"138 ","pages":"Article 109076"},"PeriodicalIF":2.8,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145269031","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":"Multidimensional mechanistic analysis elucidates spermatogenesis disruption induced by bisphenol S","authors":"Lei Xu ,&nbsp;Bin Huang ,&nbsp;Shengliang Gu ,&nbsp;Yitao Xing ,&nbsp;Fugang Zhang ,&nbsp;Wei Fu ,&nbsp;Ting Chen ,&nbsp;Zhuojun Yuan ,&nbsp;Guozheng Qin","doi":"10.1016/j.reprotox.2025.109079","DOIUrl":"10.1016/j.reprotox.2025.109079","url":null,"abstract":"<div><div>Bisphenol S (BPS), a primary substitute for bisphenol A, has led to widespread environmental exposure globally. However, the effects of BPS on spermatogenesis disruption (SD) remain contentious, and the underlying mechanisms responsible for SD induced by BPS are not fully understood. In this study, we employed a multidimensional computational strategy, integrating network toxicology, bioinformatics, systematic machine learning, single-cell analysis, and biomolecular modeling, to comprehensively elucidate the molecular mechanisms by which BPS induces SD. Our findings suggest that BPS may disrupt spermatogenesis by interfering with multiple signaling pathways, including the cAMP signaling pathway, MAPK pathway, VEGF pathway, and PI3K-Akt pathway, thereby forming a synergistic toxic network. Through systematic screening utilizing 113 combinations of machine learning algorithms, we identified CTSK, GSTZ1, and PDE4D as core diagnostic biomarkers for SD, positing that these genes may serve as potential hub targets through which BPS disrupts spermatogenesis. Moreover, our analysis of testicular tissue-specific co-expression networks and single-cell data revealed that these hub genes are specifically expressed in testicular tissue, predominantly enriched in reproductive cell types such as Sertoli cells, peritubular myoid cells, spermatogonia, and spermatocytes. Biomolecular modeling further indicated a strong binding affinity between BPS and these hub proteins. This research not only provides critical insights into the reproductive toxicity risk assessment of BPS by elucidating its impact on spermatogenesis but also reveals novel biomarkers and potential intervention targets based on a multidimensional mechanistic analysis, thereby advancing the field of BPS reproductive toxicology.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"138 ","pages":"Article 109079"},"PeriodicalIF":2.8,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145269030","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":"Vitamin D supplementation stimulates germ cell proliferation in a restraint-stressed mouse","authors":"Rahul Kumar ,&nbsp;Lalrawngbawli Annie ,&nbsp;Guruswami Gurusubramanian ,&nbsp;Ajit Singh ,&nbsp;Vikas Kumar Roy","doi":"10.1016/j.reprotox.2025.109077","DOIUrl":"10.1016/j.reprotox.2025.109077","url":null,"abstract":"<div><div>Restraint stress in the rodent model has been used for anxiety, depression, alongside testicular dysfunction. Vitamin D regulates testicular function, but its effect on restraint stress-related testicular impairment has not been investigated yet. Therefore, the present study has investigated the effects of vitamin D on the testicular function in restraint-stressed mice. The results showed that vitamin D has improved the sperm parameters and testicular architecture. Moreover, testicular architecture showed better protection in the lower dose, along with decreased oxidative stress. Elevated apoptosis in the lower dose of vitamin D-treated mice could be a disposal mechanism for damaged germ cells. The markers of proliferation (GCNA) were elevated in both doses of vitamin D-treated groups, which showed that vitamin D stimulates germ cell proliferation, thereby improving the testicular architecture. However, PCNA expression did not change, and this could be involved in the DNA repair mechanism. The expression of NF-κB was elevated in all the stressed groups, irrespective of vitamin D treatment. Since NF-κB has pro- and anti-apoptotic effects in the testis, thus, its exact role with respect to apoptosis is not known in the present study. We examined the levels of the Vitamin D Receptor (VDR) in the testis. Our findings indicated that VDR expression was reduced in the restraint-stressed group. In conclusion, vitamin D could improve testicular function in the stressed condition by stimulating germ cell proliferation and due to proliferation, the apoptosis could have also been modulated.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"138 ","pages":"Article 109077"},"PeriodicalIF":2.8,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145259023","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":"Direct and intergenerational effects in reproductive parameters of adult male Wistar rats and their offspring after subchronic exposure to polystyrene nanoplastics","authors":"Lethícia Valencise ,&nbsp;Ana Flávia Quiarato Lozano ,&nbsp;Jorge Willian Franco de Barros ,&nbsp;Carina Funck Godoy ,&nbsp;Cibele dos Santos Borges ,&nbsp;Daniel G. Cyr ,&nbsp;Wilma De Grava Kempinas","doi":"10.1016/j.reprotox.2025.109075","DOIUrl":"10.1016/j.reprotox.2025.109075","url":null,"abstract":"<div><div>Polystyrene is among the most prevalent types of plastic debris. Polystyrene nanoplastics (PS-NP) cause several alterations in young rodent reproductive tissue and fertility. Here, we investigated if the exposure to PS-NP (500 nm) in adult (90 days-old) male Wistar rats affects reproductive parameters and causes intergenerational effects on the offspring. Study 1: animals (n = 10/group) were exposed by gavage to either distilled water (vehicle; Control group), 0.15 mg/d of PS-NP (Low Dose) or 1.50 mg/d of PS-NP (High Dose) for 60 days. Sperm quality and testosterone serum levels were measured. Study 2: the exposure protocol was repeated using only Control (n = 10) and High Dose (n = 9) groups, then blood leukocytes, histopathology of the testis and the epididymis, and fertility parameters were evaluated. At the end of treatment males (F0) were mated with untreated females (70 – 90 days-old) to produce the first generation (F1) evaluated on Study 3 (Control: n = 7; High Dose: n = 8). Study 3: intergenerational damage was assessed in the male and female offspring (F1). The presence of sperm cytoplasmic droplets and the relative number of sperm in the cauda epididymis increased in the High Dose group (Study 1), as well as the relative number of monocytes in the blood stream (Study 2). Intergenerational effects were observed such as the dysregulation of the estrous cycle of F1-females (Study 3). Given that rats exhibit significantly higher fertility rates than humans, these results could imply that long-term environmental exposure to different types of plastics might have potential consequences for human reproductive health.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"138 ","pages":"Article 109075"},"PeriodicalIF":2.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225615","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":"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}