Reproductive toxicology最新文献

{"title":"Mediation of prenatal cotinine and 8-hydroxy-2’-deoxyguanosine levels on infant birth size in the Japan Environment and Children’s Study (JECS)","authors":"Sumitaka Kobayashi ,&nbsp;Hiroyoshi Iwata ,&nbsp;Takeshi Yamaguchi ,&nbsp;Naomi Tamura ,&nbsp;Mariko Itoh ,&nbsp;Maki Tojo ,&nbsp;Keiko Yamazaki ,&nbsp;Sachiko Itoh ,&nbsp;Chihiro Miyashita ,&nbsp;Yu Ait Bamai ,&nbsp;Yukihiro Sato ,&nbsp;Yasuaki Saijo ,&nbsp;Yoshiya Ito ,&nbsp;Reiko Kishi ,&nbsp;The Japan Environment and Children’s Study Group (JECS Group)","doi":"10.1016/j.reprotox.2025.108905","DOIUrl":"10.1016/j.reprotox.2025.108905","url":null,"abstract":"<div><div>Prenatal passive and active smoking and oxidative stress are of concern because of their adverse effects on infant birth sizes. This study aimed to examine the mediation of maternal cotinine and 8-hydroxy-2’-deoxyguanosine (8-OHdG) levels during pregnancy on infant birth size by occupation. The study used data from 72,544 participants of the Japan Environment and Children’s Study (JECS), an ongoing nationwide prospective birth cohort. We used maternal cotinine in urine as a biomarker for prenatal passive and active smoking and maternal 8-OHdG as a biomarker for prenatal oxidative stress. In all participants, multiple linear regression analysis adjusted for covariates showed birth weight (95 % confidence interval; CI) at cotinine level 5 (active smoker level) decreased by 140 (127, 152) g compared to birth weight at cotinine level 1 (non-smoker level), and birth weight at the fourth quartile of 8-OHdG level decreased by 18 (12, 25) g compared to birth weight at the first quartile of 8-OHdG level. When stratified by maternal occupation, no association was found between the cotinine levels of maternal passive smoking exposure and birth size. The association between cotinine levels and decreased birth size in all the participants was mediated by 8-OHdG. The results showed that there was a maternal cotinine levels during pregnancy on birth size in infants.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"135 ","pages":"Article 108905"},"PeriodicalIF":3.3,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859475","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":"Impact of fluoride exposure on reproductive health: Insights into molecular mechanisms and health implications","authors":"Vishal Chhabra ,&nbsp;Sarasa Meenakshi ,&nbsp;Shreya Maity ,&nbsp;Dheeraj Saini ,&nbsp;Mohit Saini ,&nbsp;Krishna Murti ,&nbsp;Nitesh Kumar","doi":"10.1016/j.reprotox.2025.108907","DOIUrl":"10.1016/j.reprotox.2025.108907","url":null,"abstract":"<div><div>While the benefits of fluoride in preventing dental caries are well-established, concerns about its potential toxicity at high intake levels are rising. This review investigates the link between chronic fluoride exposure and reproductive health outcomes at the molecular level, focusing on population growth and child sex ratios in the fluorosis-affected and non-fluorosis regions. The exploration of the detrimental effects of fluoride on both male and female reproductive systems is necessary. In males, hormonal variations, alterations in spermatogenesis, capacitation, and sperm motility using molecular markers, epigenetic, transcriptomic, and proteomic data. For females, hormonal imbalances, disruptions in oocyte formation, teratogenicity (congenital disabilities), and compromised infant development due to maternal fluorosis using similar approaches. Furthermore, we explored drugs that address affected pathways, the potential benefits of vitamins and natural remedies, and lifestyle modifications to minimise adverse effects. The impact of various molecular pathways like apoptosis, autophagy, DNA damage, hormonal imbalance, inflammatory response, mitochondrial dynamics, and cell signalling pathways has been linked to reproductive toxicity induced by chronic and specific doses of fluoride. Analysing existing research and exploring potential therapeutic avenues contributes to the development of strategies to safeguard reproductive well-being in populations exposed to high fluoride levels.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"135 ","pages":"Article 108907"},"PeriodicalIF":3.3,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143833938","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 maternal PM2.5 exposure during pregnancy on cardiovascular maldevelopment in rat offspring","authors":"Shengying Yang ,&nbsp;Guiming Zhang ,&nbsp;Xinru Hong ,&nbsp;Tao Li ,&nbsp;Yang Liu ,&nbsp;Huangfeng Hong ,&nbsp;Lina Liu ,&nbsp;Hailong Wang ,&nbsp;Shuiping Wu ,&nbsp;Yulan Wang ,&nbsp;Ping Wang ,&nbsp;Qinghua Sun ,&nbsp;Chaobin Liu","doi":"10.1016/j.reprotox.2025.108906","DOIUrl":"10.1016/j.reprotox.2025.108906","url":null,"abstract":"<div><h3>Background</h3><div>Epidemiological studies suggest a link between maternal exposure to PM_2.5 during pregnancy and a higher incidence of fetal cardiovascular abnormalities. However, experimental data on the underlying mechanisms remain scarce.</div></div><div><h3>Objective</h3><div>This study aims to explore the effects of maternal PM_2.5 exposure during pregnancy on fetal cardiovascular maldevelopment in a rat model.</div></div><div><h3>Methods</h3><div>Twenty-eight pregnant rats were divided into control and PM_2.5-exposed groups according the exposure doses (<em>N</em> = 7 per group). Rats were administered with PM_2.5 suspensions corresponding to 0, 2.6, 5.5, and 11 μg/d, respectively, during gestation. On gestational day 21, neonatal hearts were collected, and levels of cardiac transcription factors (Tbx2, Tbx20, Hand2 and Gata6), MMP9, TN-C, VEGF-A, NF-κB, apoptotic markers (Bax/Bcl-2 ratio), catalase (CAT), and lipid metabolism indicators were measured.</div></div><div><h3>Results</h3><div>In the 11 μg/d group, the mRNA levels of Tbx2, Tbx20, Hand2, Gata6, MMP9, TN-C and VEGF-A, the protein levels of Tbx2, Hand2, and TN-C, and blood CAT activity were significantly reduced (<em>P</em> &lt; 0.05). Conversely, NF-κB, Bax/Bcl-2, and serum markers of dyslipidemia (TC, TG, LDH, LDL-C/HDL-C) were significantly elevated (<em>P</em> &lt; 0.05). Additionally, TN-C and Hand2 mRNA levels were reduced in the 2.6 μg/d group, and LDH level was increased in the 5.5 μg/d group (<em>P</em> &lt; 0.05).</div></div><div><h3>Conclusions</h3><div>Maternal PM_2.5 exposure during pregnancy is associated with fetal cardiovascular maldevelopments, possibly through the changes of cardiac transcription factors, vascular dysfunction, oxidative stress, apoptosis, and abnormalities of lipid metabolism.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"135 ","pages":"Article 108906"},"PeriodicalIF":3.3,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839150","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 700 MHz radiofrequency radiation (5 G lower band) on the reproductive parameters of female Wistar rats","authors":"Neha Jha ,&nbsp;Priyanka Sarsaiya ,&nbsp;Anuj Kumar Tomar ,&nbsp;Sonali Pardhiya ,&nbsp;Jay Prakash Nirala ,&nbsp;P.K. Chaturvedi ,&nbsp;Surabhi Gupta ,&nbsp;Paulraj Rajamani","doi":"10.1016/j.reprotox.2025.108910","DOIUrl":"10.1016/j.reprotox.2025.108910","url":null,"abstract":"<div><div>The advent of 5 G technology has raised concerns about its potential biological effects, particularly reproductive health being one key area of focus. This study investigated the impact of 700 MHz, a lower 5 G frequency band, on the reproductive health of female Wistar rats. The experiment analyzed the effects of short-term and long-term exposure to 700 MHz mobile radiation on female Wistar rats. Rats were divided into three groups (control, sham-exposed, and exposed), with sample sizes of n = 6 for short-term and n = 8 for long-term exposure. For short-term exposure, rats were subjected to 6 hrs of radiation daily for 10 days, while for long-term exposure, rats exposed 4 hrs daily for 60 days. Physiological parameters, including estrous cyclicity, were monitored, and histopathological and biochemical analyses were conducted on harvested ovaries. Comet assay was performed to assess DNA damage. The results indicated no changes in estrous cycles or comet assay parameters in either exposure group. Serological hormone levels, including estradiol and progesterone, remained within normal ranges, but a slight yet significant increase in testosterone levels was observed in exposed groups. Oxidative stress markers revealed elevated malondialdehyde (MDA) levels and significant decreases in superoxide dismutase (SOD), total sulfhydryl content, and ferric reducing antioxidant power (FRAP) in exposed ovaries. Histopathological analysis showed no significant changes in ovarian morphology in short-term exposure but revealed alterations, including cystic follicles and abnormal vasculature, in long-term exposure. These findings suggest that 700 MHz radiation may induce oxidative stress and tissue changes in ovarian samples over prolonged exposure.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"135 ","pages":"Article 108910"},"PeriodicalIF":3.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825402","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":"Exposure to disinfection by-products and risk of diminished ovarian reserve: Case-control evidence and cellular metabolomic insights","authors":"Yichang Tian ,&nbsp;Zelin Wang ,&nbsp;Cong Wang ,&nbsp;Ying Fang ,&nbsp;Jiaqi Wu ,&nbsp;Xuehan Zhao ,&nbsp;Qin Wang ,&nbsp;Jing Zhang ,&nbsp;Yi Yang ,&nbsp;Xiaokui Yang","doi":"10.1016/j.reprotox.2025.108901","DOIUrl":"10.1016/j.reprotox.2025.108901","url":null,"abstract":"<div><div>Disinfection of drinking water is a critical measure for ensuring water safety and controlling waterborne infectious diseases. However, during the disinfection process, a variety of disinfection by-products (DBPs), some of which exhibit reproductive toxicity, are generated. This study aimed to assess whether DBP exposure contributes to the risk of diminished ovarian reserve (DOR) and explored the underlying metabolic mechanisms. A total of 182 participants, including 91 healthy women and 91 women with DOR, were recruited for a case-control study conducted between October 2023 and February 2024. Serum concentrations of DBPs, including dibromoacetic acid (DBAA), monochloroacetic acid (MCAA), dichloroacetic acid (DCAA), trichloroacetic acid (TCAA), chlorate, and perchlorate, were measured to evaluate DBP exposure. Key indicators for evaluating DOR included antral follicle count (AFC), anti-Mullerian hormone (AMH), and follicle-stimulating hormone (FSH). All six DBPs were higher in DOR patients (all <em>p</em> &lt; 0.05). After controlling for covariates, all DBPs showed negative correlations with AMH and AFC, positive correlations with basal FSH, and a significant association with the risk of DOR (all <em>p</em> &lt; 0.05). To further investigate the underlying mechanisms, we conducted an <em>in vitro</em> study using human ovarian granulosa cell line (KGN). KGN cells were exposed to DBAA and perchlorate for 48 hours, and metabolomic analysis was performed to identify altered metabolic pathways. Metabolomics data suggested that DBAA and perchlorate might have contributed to DOR by disrupting arginine biosynthesis and purine metabolism, respectively. In conclusion, DBPs exposure might have contributed to DOR risk by disrupting granulosa cell (GC) metabolism.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"135 ","pages":"Article 108901"},"PeriodicalIF":3.3,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804154","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 endocrine disrupting chemicals targeting NTD-related hub genes during pregnancy via in silico analysis","authors":"Junjie Guo,&nbsp;Hao Yu,&nbsp;Yujun Guo,&nbsp;Jinming Liu,&nbsp;Yuzhu Chen,&nbsp;Zhaozhu Li","doi":"10.1016/j.reprotox.2025.108904","DOIUrl":"10.1016/j.reprotox.2025.108904","url":null,"abstract":"<div><div>Neural tube defects (NTDs) represent severe congenital malformations of the central nervous system with multifactorial etiology, involving intricate gene-environment interactions that remain incompletely characterized. Endocrine disrupting chemicals (EDCs) are exogenous substances with hormone-disrupting properties that are ubiquitous in our surroundings. These chemicals pose a significant threat to human health, contributing to a range of diseases. Pregnant women are particularly vulnerable to the effects of EDCs, as these substances can traverse the placental barrier and impact the development of both the placenta and fetus. This study utilized placental and fetal transcriptome data to identify hub genes associated with NTDs during pregnancy. By leveraging the Comparative Toxicogenomics Database (CTD), we predicted the EDCs targeting these hub genes and performed molecular docking to assess their interactions. Our findings revealed four hub genes (CTSC, FCER1G, ITGB2, and LYVE1) in NTDs, with 72 EDCs identified as their targets. Molecular docking demonstrated that atrazine, bisphenol A (BPA) and diuron exhibited stable affinity with the proteins encoded by hub genes. These findings provide new insights into the environmental endocrine disruptors that affect the development of NTDs during pregnancy.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"134 ","pages":"Article 108904"},"PeriodicalIF":3.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776922","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":"The role of ATG7-mediated ferroptosis in formaldehyde-induced ovarian injury in rats","authors":"Kun Mao ,&nbsp;Hao-zhe Yan ,&nbsp;Jia-qi Yang ,&nbsp;Zi-xin Yin ,&nbsp;Xin-qi Gao ,&nbsp;Hao-fu Liu ,&nbsp;Heng Su ,&nbsp;Yuan-yuan Geng ,&nbsp;Pan Ge ,&nbsp;Dang-xia Zhou","doi":"10.1016/j.reprotox.2025.108902","DOIUrl":"10.1016/j.reprotox.2025.108902","url":null,"abstract":"<div><h3>Background</h3><div>To investigate the mechanisms of toxicological damage of formaldehyde to the female reproductive system</div></div><div><h3>Methods</h3><div>A Mendelian randomization method was used to predict a causal relationship between ferroptosis genes and female infertility. Changes in the structure and function of rat ovaries were observed by HE staining and transmission electron microscopy. Combined with molecular experiments, we verified the alterations of GSH, iron ions, MDA levels, and the expression of ferroptosis genes.</div></div><div><h3>Results</h3><div>Mendelian randomization suggested a significant causal relationship between ATG7 and female infertility. Animal experiments showed that formaldehyde caused abnormal follicular maturation and ovarian mitochondrial alterations. Meanwhile, formaldehyde induced elevated levels of iron ions and MDA and decreased GSH levels. Further detection by Western blotting and qRT-PCR revealed that the expression of the ferroptosis marker gene GPX4 decreased and ATG7 increased in the ovary after formaldehyde stimulation.</div></div><div><h3>Conclusions</h3><div>Formaldehyde affected the structure and physiological function of rat ovary by activating the expression level of ATG7 and inhibiting the activity of GPX4, which caused iron overload and elevated levels of peroxides, leading to the occurrence of ferroptosis in ovarian tissue.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"134 ","pages":"Article 108902"},"PeriodicalIF":3.3,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754355","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":"Uteroplacental adaptations to an altered gestational environment: Advances in clinical, animal model and in vitro studies","authors":"Jayanth Ramadoss,&nbsp;Michael C. Petriello,&nbsp;Madhu Chauhan","doi":"10.1016/j.reprotox.2025.108900","DOIUrl":"10.1016/j.reprotox.2025.108900","url":null,"abstract":"","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"134 ","pages":"Article 108900"},"PeriodicalIF":3.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731354","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":"TERT's protective effect on trophoblast cells: Reducing mitochondrial ROS","authors":"Zongyuan Tian,&nbsp;Xueran Wang,&nbsp;Yingyi Luan,&nbsp;Ruixia Liu","doi":"10.1016/j.reprotox.2025.108899","DOIUrl":"10.1016/j.reprotox.2025.108899","url":null,"abstract":"<div><h3>Objective</h3><div>The principal objective of this project is to elucidate the ameliorating function of telomerase reverse transcriptase (TERT) on placental trophoblast dysfunction and its associated mitochondrial dysfunction.</div></div><div><h3>Methods</h3><div>We utilised 50 μM hydrogen peroxide (H₂O₂) to induce an oxidative stress model in HTR-8/SVneo cells (NC group and OS group), subsequently establishing three experimental conditions via lentiviral transfection: untreated controls (Con group), TERT-overexpressing cells (OE group), and empty vector-transfected negative cells (Neg group). In order to explore the role of mitochondrial TERT, we employed the Src kinase familyinhibitor PP1 (4-Amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-<em>d</em>]pyrimidine), a cell-permeable small molecule specifically blocking the translocation of TERT in HTR-8/SVneo cells with overexpressed TERT. We established four experimental conditions: untreated overexpression group (OE group), H₂O₂-stimulated group (OS group), co-treatment group of H₂O₂ and PP1 (PP1 OS group), and PP1 treatment group alone (PP1 group). The expression and localization of TERT were analysed via qRT-PCR, immunofluorescence, and Western blotting. In addition, the cellular functions (viability, migration, invasion) were assessed using CCK-8, Calcein AM/PI staining, wound healing assay and Transwell assay. Mitochondrial integrity was thoroughly assessed using a mitochondrial membrane potential assay, an ATP content assay, a mtDNA copy number quantification and a mitochondrial morphology assay.</div></div><div><h3>Results</h3><div>The OE group demonstrated significantly reduced reactive oxygen species (ROS) levels compared to Con and Neg groups, accompanied by enhanced cellular viability and improved migratory and invasive capacities. Mitochondrial functional analyses revealed superior outcomes in the OE group, including stabilized mitochondrial membrane potential and ATP production, maintained mtDNA copy numbers, and preserved mitochondrial ultrastructure. Conversely, pharmacological inhibition with PP1 - a Src kinase family inhibitor that blocks TERT mitochondrial translocation - effectively abolished these protective effects. PP1-treated cells exhibited exacerbated oxidative stress, impaired cell viability, and diminished motility, confirming the essential role of mitochondrial-localized TERT in cellular homeostasis.</div></div><div><h3>Conclusions</h3><div>Elevated mitochondrial TERT levels were able to effectively mitigate the cellular functional damage induced by elevated ROS levels by maintaining mitochondrial stability. The above findings provide a theoretical basis for the development of intervention strategies for pregnancy-related disorders based on the regulation of mitochondrial TERT function.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"134 ","pages":"Article 108899"},"PeriodicalIF":3.3,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143696041","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":"Prenatal exposure to phenanthrene impairs spermatogenesis and fertility by elevating apoptosis, altering gene expression, and disrupting steroidogenesis in adult male mice across two generations","authors":"Azar Afshar ,&nbsp;Hamid Nazarian ,&nbsp;Fatemeh Fadaefathabadi ,&nbsp;Reza Mastery-Farahani ,&nbsp;Fakhroddin Aghajanpour ,&nbsp;Reza Soltani ,&nbsp;Maryam Salimi ,&nbsp;Mohsen Nourozian ,&nbsp;Gholamreza Hassanzadeh","doi":"10.1016/j.reprotox.2025.108897","DOIUrl":"10.1016/j.reprotox.2025.108897","url":null,"abstract":"<div><h3>Background</h3><div>Phenanthrene, a polycyclic aromatic hydrocarbon, can enter the human body via various routes and affect reproductive health. Its low molecular weight enables its transfer from the mother to the fetus. However, comprehensive research on its effects on reproductive system development is lacking. This study aimed to examine the impacts of prenatal phenanthrene exposure on the reproductive systems of both the immediate offspring and their progeny.</div></div><div><h3>Methods</h3><div>Pregnant mice were divided into three groups: control, sham, and phenanthrene. From the detection of the vaginal plug until pregnancy day 18, mice in the phenanthrene group were administered phenanthrene solution (60 μg/kg), while sham mice received corn oil on alternate days. Following birth, male offspring were maintained without intervention until PND56. After puberty, a portion of these males were bred, while others were euthanized for histological and molecular analyses. The subsequent generation was born and developed under standard conditions without intervention, and underwent procedures similar to those of the first generation.</div></div><div><h3>Results</h3><div>The study revealed that exposure to phenanthrene during fetal development, across two consecutive generations, led to a reduction in the expression of genes associated with mitosis and meiosis, while simultaneously increasing the rate of cell death. Additionally, the research found that a decline in Leydig cells resulted in decreased serum testosterone levels, which subsequently led to diminished quality and quantity of sperm.</div></div><div><h3>Conclusion</h3><div>Prenatal phenanthrene exposure, by disrupting gene expression and steroidogenesis, causes impaired testicular tissue function, reduced spermatogenesis, and ultimately reduced male fertility rates in the F1 and F2.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"134 ","pages":"Article 108897"},"PeriodicalIF":3.3,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711171","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}