You-wen Luo , Xia-lian Zhu , Zhi-min Yang , Jian-hua Zhou , Tong Tao , Bing-hai Chen , Song-lin Qin , Bo-long Liu , Wei Hu
{"title":"Adrenomedullin gene delivery rescues estrogen production in Leydig cells via the inhibition of TGF-β1/Smads signaling pathway","authors":"You-wen Luo , Xia-lian Zhu , Zhi-min Yang , Jian-hua Zhou , Tong Tao , Bing-hai Chen , Song-lin Qin , Bo-long Liu , Wei Hu","doi":"10.1016/j.reprotox.2025.108834","DOIUrl":"10.1016/j.reprotox.2025.108834","url":null,"abstract":"<div><div>Our previous findings demonstrated that adrenomedullin (ADM) protects against the reduction in testosterone production and apoptosis of Leydig cells both in vitro and in vivo. In this study, we investigated whether ADM could preserve estrogen production in Leydig cells by suppressing the transforming growth factor-β1 (TGF-β1) / Smads signaling pathway. Leydig cells were treated with lipopolysaccharide (LPS) and recombinant adenovirus ADM (Ad-ADM), an adeno-associated viral vector expressing ADM. Cell viability and cytochrome P450 aromatase (P450arom) activity were assessed. Estrogen, testosterone, and TGF-β1 concentrations in the culture medium were measured. Additionally, the gene expression and protein levels of CYP19, TGF-β1, and Smads were evaluated. The results indicated that Ad-ADM mitigated the reductions in Leydig cell viability and testosterone production, counteracted the decreases in P450arom activity, and restored CYP19 gene expression and protein levels in LPS-treated cells. Moreover, Ad-ADM reduced the elevated gene expression and protein levels of Smads and TGF-β1 induced by LPS. Based on these findings, we propose that ADM safeguards estrogen production in Leydig cells by inhibiting the TGF-β1/Smads signaling pathway.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108834"},"PeriodicalIF":3.3,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142966470","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":"Ampligo® 150 ZC affect the expression of sex hormone receptors and cell proliferation marker in female rabbit ovary: Protective effects of thyme essential oil and vitamin C","authors":"Chahrazed Makhlouf , Hassina Khaldoun , Louisa Béchohra , Nacima Djennane , Amina Settar , Dalila Tarzaali , Yasmine Oularbi , Smail Krabi , Soumya Bokreta , Nacira Zerrouki Daoudi","doi":"10.1016/j.reprotox.2025.108833","DOIUrl":"10.1016/j.reprotox.2025.108833","url":null,"abstract":"<div><div>Pesticides tend to cause serious reproductive defects, disturbing endocrine functions and reducing fertility, especially in females. The objective of this work was to identify the reprotoxic effects of Ampligo® 150 ZC (AP), a mixture formulation of lambda cyhalothrin and chlorantraniliprole, on the ovary of female rabbits (<em>Oryctolagus cuniculus</em>) and the possible protective effect of co-treatment with thyme essential oil (TEO), extracted from (<em>Thymus vulgaris</em>) species, and vitamin C (vit C). Twenty female rabbits were divided into four equal groups (n = 5): Control (distilled water), AP (20 mg/ kg bw of the insecticide mixture every other day, by gavage for 28 days), AP+TEO (20 mg/ kg bw of AP + 0.5 mg/ kg bw of TEO every other day), and AP+TEO+Vit C (20 mg/ kg bw of AP + 0.5 mg/ kg bw of TEO + 200 mg/ kg bw of vitamin C every other day). The effects were tested on body weight, ovary histomorphometry, and immunohistochemical expression of AFP, estrogen receptor (ER), and progesterone receptor (PR). The results revealed that AP decreased body and ovarian weights, caused ovarian histological damages, and increased collagen fiber deposition. The immunostaining of the ovary showed a significant (p < .001) increase in AFP and decrease in both ER and PR expressions. In the opposite, co-administration of TEO and vitamin C was effective in improving all caused alterations. In conclusion, combined use of TEO and vitamin C ameliorated the toxic effects of Ampligo® on the ovary in female rabbits.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108833"},"PeriodicalIF":3.3,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142954142","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}
Zechen Niu , Huanhuan Zhang , Chunzhou Cai , Ting Yang , Tian Ma , Dingqiao Xu , Dongxiao Cui , Yuping Tang
{"title":"The mechanisms of tripterygium glycosides-induced reproductive toxicity and detoxification strategies","authors":"Zechen Niu , Huanhuan Zhang , Chunzhou Cai , Ting Yang , Tian Ma , Dingqiao Xu , Dongxiao Cui , Yuping Tang","doi":"10.1016/j.reprotox.2025.108830","DOIUrl":"10.1016/j.reprotox.2025.108830","url":null,"abstract":"<div><div>Tripterygium glycosides (TG) is a widely used preparation in the treatment of rheumatoid arthritis (RA), nephrotic syndrome and diabetic nephropathy. Although the clinical efficacy is definite, the side-effects on reproductive system limit its wide application. It is of great significance to take measures to alleviate its reproductive toxicity and expand its clinical use. The mechanism of TG-induced reproductive toxicity involves oxidative stress, inflammation, apoptosis, and metabolism imbalance, which lead to adverse effects on male and female reproductive organs. To mitigate these effects, detoxification strategies including combining TG with other agents have been proved to counteract its toxicity. This review will provide information for the studies of TG-induced reproductive toxicity, and also provide insights for developing novel strategies to alleviate the reproductive side effects of TG.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108830"},"PeriodicalIF":3.3,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142954143","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 the impact of environmental factors on male reproductive health through epigenetics","authors":"Yi Zhang , Jing-Yan Song , Zhen-Gao Sun","doi":"10.1016/j.reprotox.2025.108832","DOIUrl":"10.1016/j.reprotox.2025.108832","url":null,"abstract":"<div><div>Male infertility has become an increasingly severe global health issue, with its incidence significantly rising over the past few decades. This paper delves into the crucial role of epigenetics in male reproductive health, focusing particularly on the effects of DNA methylation, histone modifications, chromatin remodeling and non-coding RNAs regulation on spermatogenesis. Exposure to various environmental factors can cause sperm DNA damage, leading to epigenetic abnormalities. Among these factors, we have discussed heavy metals (including Zinc, Cadmium, Arsenic, Copper), phthalates, electromagnetic radiation, and temperature in detail. Notably, aberrations in DNA methylation are closely associated with various symptoms of male infertility, and histone modifications and chromatin remodeling are essential for sperm maturation and function. By synthesizing existing literature and experimental data, this narrative review investigates how environmental factors influence male reproductive health through epigenetic mechanisms, thus providing new theoretical foundations and practical guidelines for the early diagnosis and treatment of male infertility.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108832"},"PeriodicalIF":3.3,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142954139","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}
Julia R. Varshavsky , Juleen Lam , Courtney Cooper , Patrick Allard , Jennifer Fung , Ashwini Oke , Ravinder Kumar , Joshua F. Robinson , Tracey J. Woodruff
{"title":"Analyzing high-throughput assay data to advance the rapid screening of environmental chemicals for human reproductive toxicity","authors":"Julia R. Varshavsky , Juleen Lam , Courtney Cooper , Patrick Allard , Jennifer Fung , Ashwini Oke , Ravinder Kumar , Joshua F. Robinson , Tracey J. Woodruff","doi":"10.1016/j.reprotox.2024.108725","DOIUrl":"10.1016/j.reprotox.2024.108725","url":null,"abstract":"<div><div>While high-throughput (HTP) assays have been proposed as platforms to rapidly assess reproductive toxicity, there is currently a lack of established assays that specifically address germline development/function and fertility. We assessed the applicability domains of yeast (<em>S. cerevisiae)</em> and nematode <em>(C. elegans)</em> HTP assays in toxicity screening of 124 environmental chemicals, determining their agreement in identifying toxicants and their concordance with reproductive toxicity <em>in vivo</em>. We integrated data generated in the two models and compared results using a streamlined, semi-automated benchmark dose (BMD) modeling approach. We then extracted and modeled relevant mammalian <em>in vivo</em> data available for the matching chemicals included in the Toxicological Reference Database (ToxRefDB). We ranked potencies of common compounds using the BMD and evaluated correlation between the datasets using Pearson and Spearman correlation coefficients. We found moderate to good correlation across the three data sets, with r = 0.48 (95 % CI: 0.28–1.00, p<0.001) and r<sub>s</sub> = 0.40 (p=0.002) for the parametric and rank order correlations between the HTP BMDs; r = 0.95 (95 % CI: 0.76–1.00, p=0.0005) and r<sub>s</sub> = 0.89 (p=0.006) between the yeast assay and ToxRefDB BMDs; and r = 0.81 (95 % CI: 0.28–1.00, p=0.014) and r<sub>s</sub> = 0.75 (p=0.033) between the worm assay and ToxRefDB BMDs. Our findings underscore the potential of these HTP assays to identify environmental chemicals that exhibit reproductive toxicity. Integrating these HTP datasets into mammalian <em>in vivo</em> prediction models using machine learning methods could further enhance their predictive value in future rapid screening efforts.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"131 ","pages":"Article 108725"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiang-Zhu Yan , Jia Peng , Yu-Qing Liu , Ruo-Nan Fan , Xin-Yi Ni , Ling Gong , Dan-Ni Zhang , Xin Huang , Shu-Hua Tan , Hai-Long Wang
{"title":"Mixed exposure to PFOA and PFOS induces oocyte apoptosis and subfertility in mice by activating the Hippo signaling pathway","authors":"Xiang-Zhu Yan , Jia Peng , Yu-Qing Liu , Ruo-Nan Fan , Xin-Yi Ni , Ling Gong , Dan-Ni Zhang , Xin Huang , Shu-Hua Tan , Hai-Long Wang","doi":"10.1016/j.reprotox.2024.108829","DOIUrl":"10.1016/j.reprotox.2024.108829","url":null,"abstract":"<div><div>Per- and polyfluoroalkyl substances (PFAS) are synthetic perfluorinated compounds known for their persistence in the environment and reproduction toxicity. PFAS, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), have been identified in the follicular fluid of infertile women. However, the specific of PFOA and PFOS mixture on oocyte quality and female fertility remain unclear. In this study, we exposed female mice to combination of PFOA and PFOS to investigate the underlying mechanisms impairing fertility and oocyte maturation. Our results showed that exposure to the mixture induced epigenetic alterations and DNA damage in oocytes, impairing meiosis. Additionally, mitochondrial dysfunction caused by the exposure to the mixture led to oxidative stress and apoptosis in the oocytes. The reduction in oocyte quality resulted in a decrease in blastocyst quality and litter size. Furthermore, single-cell transcriptome analysis indicated that exposure to the mixture disrupted energy metabolism and triggered apoptosis, possibly through the activation of the Hippo signaling pathway. Overall, our results suggest that exposure to PFOA and PFOS mixture impairs the fertility in mice through the activation of the Hippo signaling pathway-induced oocytes apoptosis.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108829"},"PeriodicalIF":3.3,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922789","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}
Jay S. Mishra , Bradley Bosse , Kara K. Hoppe , Kristen Malecki , Scott J. Hetzel , Sathish Kumar
{"title":"Perfluoroalkyl substances (PFAS) exposure and preeclampsia risk: Impaired angiogenesis through suppression of VEGF signaling","authors":"Jay S. Mishra , Bradley Bosse , Kara K. Hoppe , Kristen Malecki , Scott J. Hetzel , Sathish Kumar","doi":"10.1016/j.reprotox.2024.108827","DOIUrl":"10.1016/j.reprotox.2024.108827","url":null,"abstract":"<div><div>Per- and polyfluoroalkyl substances (PFAS) are linked to preeclampsia (PE), a condition involving abnormal angiogenesis. Prior research on this association has been inconclusive. We investigated the relationship between maternal PFAS exposure and PE risk in Wisconsin. We also examined if PFAS disrupts angiogenesis and, if so, what mechanisms are involved. We conducted a case-control study with 40 PE cases and 40 controls. Maternal serum was analyzed for 38 different PFAS compounds using LC MS/MS. Functional in vitro experiments assessed PFOS effects on angiogenesis and mechanisms. Maternal serum samples from women with PE exhibited significantly higher PFOS and PFHPS concentrations than controls. After adjusting for confounders, each log-scale IQR increase in PFOS and PFHPS concentrations was associated with a 7.18-fold (95 % CI: 2.24, 23.0) and 5.40-fold (95 % CI: 1.81, 16.1) higher odds of PE, respectively. Furthermore, PFOS and PFHPS were positively associated with sFLT1 levels and the sFLT1/PLGF ratio. In vitro experiments revealed that PFOS exposure impaired HUVEC proliferation, migration, and tube formation, essential processes for angiogenesis. The membrane-based antibody array showed that PFOS decreased expression of multiple angiogenic proteins, including I-TAC, uPAR, VEGFR2, MMP-1, IL-1α, Angiopoietin-2, IL-1β, PECAM-1, TIE-2, and TIMP-2. The qPCR analysis demonstrated that PFOS decreased VEGFR2, the upstream target of VEGF, at the transcriptional level. In conclusion, elevated PFAS, especially PFOS and PFHPS, are linked to increased PE risk. PFOS may suppress angiogenesis via attenuated VEGFR2-mediated signaling, providing a molecular mechanism linking PFAS and PE pathogenesis.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108827"},"PeriodicalIF":3.3,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896576","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":"Computational insights into maternal environmental pollutants and folate pathway regulation","authors":"Adarsh Kumar Shukla, Shadab Ahamad, Prachi Kukshal","doi":"10.1016/j.reprotox.2024.108825","DOIUrl":"10.1016/j.reprotox.2024.108825","url":null,"abstract":"<div><div>Exposure to environmental pollutants during pregnancy can adversely affect fetal growth and postnatal development. While numerous studies have explored the interaction between environmental toxic chemicals and the folate pathway, few have examined their inhibitory effects on key targets. This computational study identified 27 maternal environmental toxicants using the Comparative Toxicogenomics Database (CTD) and analyzed them to identify their targets. Molecular modeling, docking, and dynamics simulations revealed that folate receptors (FOLR1, FOLR2, and FOLR3) and transporters (SLC19A1 and SLC46) are major targets. Among these, FOLR3 exhibited the strongest interactions with toxicants such as Dichlorodiphenyltrichloroethane (DDT), Bisphenols, Dioxin, and other investigated toxicants. Toxicity profiling showed that even minimal exposure to these pollutants significantly impacts maternal health and disrupts folate metabolism, leading to fetal malformations. This study highlights the critical role of maternal toxicants in hindering the folate pathway, with severe implications for fetal development.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108825"},"PeriodicalIF":3.3,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142897282","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}
Manal Mohammad Morsy , Heba A. Hassan , Reham M. Morsi , Ola Elsayed Nafea , Azza I. Farag , Rania Saad Ramadan
{"title":"Alogliptin attenuates testicular damage induced by monosodium glutamate in both juvenile and adult male rats by activating autophagy: ROS dependent AMPK/mTOR","authors":"Manal Mohammad Morsy , Heba A. Hassan , Reham M. Morsi , Ola Elsayed Nafea , Azza I. Farag , Rania Saad Ramadan","doi":"10.1016/j.reprotox.2024.108826","DOIUrl":"10.1016/j.reprotox.2024.108826","url":null,"abstract":"<div><div>Monosodium glutamate (MSG) is one of the most commonly used food additives, known for its adverse health effects. Alogliptin (ALO) is a highly selective dipeptidyl peptidase-4 inhibitor, but its role in male reproductive function remains debated. The study was designed to evaluate and compare the potential of ALO in mitigating MSG-induced testicular toxicity in juvenile and adult male rats. Juvenile and adult male rats were treated with either MSG or pretreated with ALO before MSG administration. The rats then received ALO and MSG concurrently for 28 days. Testicular tissues were isolated and subjected to histo-biochemical and molecular assessments. Our results demonstrated that ALO reversed MSG-induced testicular injury, as evidenced by the restoration of reproductive hormone balance (increased serum luteinizing hormone and testosterone concentrations), suppression of oxidative stress injury (decreased testicular malondialdehyde, increased superoxide dismutase activity, and minimal 8-hydroxy-2′-deoxyguanosine immunoreactivity), inflammation (reduced testicular tumor necrosis factor-alpha levels), and fibrosis (decreased testicular collagen fiber deposition). Additionally, ALO impeded apoptosis and activated autophagy by decreasing caspase-3 activity, stimulating the AMPK/mTOR pathway, downregulating <em>Bax</em> and <em>SQSTM-1/p62</em> expression, upregulating <em>Bcl2</em> and <em>Beclin 1</em>, promoting testicular proliferation (increased number of proliferating cell nuclear antigen-positive cells in the testis), restoring glycogen content in the testis (mild to moderate periodic acid-Schiff reaction), and preserving testicular architecture. MSG induced more severe adverse testicular effects in juvenile rats, while ALO pretreatment was more protective in adult rats. ALO's anti-inflammatory, antioxidant, antiapoptotic, pro-autophagic, antifibrotic, and proliferative actions in the testis suggest its promising potential for combating male reproductive dysfunction.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108826"},"PeriodicalIF":3.3,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142897280","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}
Anderson Tadeu de Araújo-Ramos, Anderson Joel Martino-Andrade
{"title":"Role of the endocannabinoid system in gonadal development: Implications for endocrine disruption and reproductive toxicity","authors":"Anderson Tadeu de Araújo-Ramos, Anderson Joel Martino-Andrade","doi":"10.1016/j.reprotox.2024.108822","DOIUrl":"10.1016/j.reprotox.2024.108822","url":null,"abstract":"<div><div>The endocannabinoid system (ECS) plays a pivotal role in reproductive physiology, including gonadal development, though its influence on testis and ovary development has only recently gained attention. The ECS comprises lipid-derived ligands such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG), along with cannabinoid receptors CB1 and CB2, which are expressed in various gonadal cells. Emerging research indicates that ECS signaling is critical for testosterone synthesis and gonadal cell proliferation and differentiation. This review explores the expression and function of ECS components in developing gonads, highlighting the differential roles of CB1 and CB2 receptors in species-specific contexts. Furthermore, the ECS has been suggested to be involved in the adverse effects of endocrine-disrupting chemicals (EDCs) on reproductive development. EDCs, such as phthalates, may interfere with ECS signaling, potentially leading to reproductive abnormalities that resemble the human Testicular Dysgenesis Syndrome (TDS). Understanding the molecular interactions between EDCs and the ECS could reveal novel mechanisms underlying reproductive toxicities. Future research should focus on the detailed localization and temporal expression of ECS components in fetal gonads, the mechanisms of cannabinoid-mediated testosterone inhibition, and the potential direct interaction of EDCs with the ECS. This knowledge could be crucial for developing strategies to mitigate reproductive health risks associated with EDC exposure.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108822"},"PeriodicalIF":3.3,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872591","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}