Reproductive toxicology最新文献

{"title":"The Maternal-Placental-Fetal Liver Axis: A Mechanistic Framework for Understanding Benzene Developmental Hematotoxicity.","authors":"Perri M Grant, Megan E Cull, Holly Mackay, Caitlyn I Kirkpatrick, Louise M Winn","doi":"10.1016/j.reprotox.2026.109385","DOIUrl":"https://doi.org/10.1016/j.reprotox.2026.109385","url":null,"abstract":"<p><p>Benzene is a ubiquitous environmental pollutant and a human hematotoxicant and carcinogen. Increasing epidemiological and experimental evidence links in utero benzene exposure to adverse pregnancy outcomes, altered fetal development, and increased childhood leukemia risk. Benzene toxicity is initiated through metabolism into reactive intermediates, primarily by cytochrome P450 2E1 (CYP2E1) and myeloperoxidase. These enzymes are expressed not only in the maternal liver but also in the placenta and fetal liver, indicating that multiple compartments may contribute to benzene toxicity during pregnancy. Despite these observations, the mechanisms linking maternal exposure to fetal hematotoxicity remain incompletely understood, as existing studies have largely examined maternal, placental, and fetal effects independently, with the placenta often treated as a passive barrier rather than an active regulator of developmental toxicity. We propose the maternal-placental-fetal liver axis as a mechanistic framework for understanding in utero benzene developmental hematotoxicity, and discuss three biologically plausible bioactivation routes across this axis: maternal hepatic metabolism, placental bioactivation, and direct fetal liver metabolism. We further examine how fetal injury may arise through complementary mechanisms: direct toxicity from transplacental transfer of benzene and its reactive metabolites, and indirect toxicity, whereby benzene-induced placental dysfunction alters the intrauterine environment and may drive secondary fetal injury. We suggest a model where placental dysfunction may amplify, rather than independently drive, fetal benzene toxicity. The maternal-placental-fetal liver axis integrates maternal metabolism, placental biology, and fetal susceptibility, providing a mechanistic framework for understanding the pathways underlying benzene-induced developmental hepatotoxicity and its potential contribution to childhood leukemia.</p>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":" ","pages":"109385"},"PeriodicalIF":3.4,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224781","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":"\"Mirabegron as a Protective Agent in Testosterone-Induced Prostate and Seminal Vesicle Toxicity: Insights into PCNA and TLR-4 Pathways\".","authors":"Sarah Sameh Abdel-Hameed, Mahmoud El-Daly, Asmaa I Matouk","doi":"10.1016/j.reprotox.2026.109387","DOIUrl":"https://doi.org/10.1016/j.reprotox.2026.109387","url":null,"abstract":"<p><strong>Background: </strong>Testosterone is an androgenic hormone and one of the anabolic steroids used in the management of conditions related to hypogonadism as well as to enhance performance in bodybuilders. Prolonged use of testosterone has been linked to adverse outcomes on male reproductive organs. Mirabegron, a β3- adrenergic receptor agonist, is used to alleviate symptoms of overactive bladder and recently, it has shown substantial antioxidant and antinflammmatory effects.</p><p><strong>Aim: </strong>This study was designed to investigate the potential protective effects of mirabegron against testosterone induced-toxicity on prostate and seminal vesicle tissues via modulating oxidative stress, inflammation and androgenic activities.</p><p><strong>Methods: </strong>Male Wistar rats (200 to 250g) were divided into three groups (n = 8); control; received vehicle, testosterone; received testosterone enanthate (3mg/kg, S.C.), and testosterone + mirabegron; received testosterone (3mg/kg, S.C.) and mirabegron (10mg/kg, P.O.) concurrently. Treatments and vehicle were administrated daily for 4 weeks.</p><p><strong>Results: </strong>Mirabegron attenuated the testosterone-induced changes on serum levels of testosterone, FSH and LH as well as reduced prostatic 5α-reductase 1 (5AR1) (0.9433 ± 0.09597ng/mg) levels. Mirabegron improved the testosterone-induced histopathological alterations of the prostate and seminal vesicle tissues. Further, it reduced prostatic TGF-β1 level (42.93 ± 3.593pg/mg) and increased GSH content in both prostatic and seminal vesicle tissues ((25.59 ± 0.8877 and 31.70 ± 0.895 µmol/mg; respectively. Additionally, mirabegron prophylactic treatment suppressed testosterone-induced increase of oxidative stress, inflammatory and proliferative mediators, including MDA, total nitrite, iNOS, TLR4, IL-1β, PCNA, and procaspase-3.</p><p><strong>Conclusion: </strong>Mirabegron mitigated the damage on prostate and seminal vesicle tissues induced by testosterone through its antioxidant and anti-inflammatory activities.</p>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":" ","pages":"109387"},"PeriodicalIF":3.4,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224778","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":"Low-level Exposure to Trifluoroacetic Acid May Induce Testicular Damage in Adolescent Mice via Ribotoxic Stress Response and NLRC5-PANoptosome-related Signaling.","authors":"Du Haoyue, Jiawei Lei, Mingxin Bai, Xueqin Shen, Kang Li, Hu Fu, Yongfei Zhu","doi":"10.1016/j.reprotox.2026.109386","DOIUrl":"https://doi.org/10.1016/j.reprotox.2026.109386","url":null,"abstract":"<p><p>Trifluoroacetic acid (TFA) is considered a per- and polyfluoroalkyl substance (PFAS) by the European Chemicals Agency, yet its potential reproductive toxicity remains poorly understood. Here, we investigated the testicular effects and underlying mechanisms of TFA exposure in adolescent male mice. Based on environmental and potential dietary exposure levels, available toxicological and risk-assessment information, and the findings of our preliminary experiment, mice were orally administered TFA at 0.0042, 0.042, 0.42, or 4.2mg/kg/day for 21 days, followed by a 7-day recovery period. Residual TFA remained detectable in the serum and testes after the recovery period, and doses ≥ 0.042mg/kg/day induced Leydig cell and spermatogenic cell damage, accompanied by reduced testosterone levels. TFA exposure also increased testicular oxidative stress (OS) and activated the ribotoxic stress response (RSR) and NLRC5-PANoptosome-related signaling. These cellular stress responses were associated with activation of PANoptosis-related pathways, involving pyroptosis, apoptosis, and necroptosis, and ultimately contributed to testicular tissue injury and impaired testicular function. Collectively, our findings demonstrate that TFA exposure at environmentally and risk-assessment-relevant levels induces testicular injury in adolescent male mice and identify a potential mechanistic link between OS, RSR, NLRC5-PANoptosome-related signaling, and PANoptosis. These findings provide new insights into the reproductive toxicity of TFA and highlight the need for further evaluation of its potential health risks.</p>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":" ","pages":"109386"},"PeriodicalIF":3.4,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224772","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":"Plastics in human reproductive tissues: A systematic review of detection, characterization, and effects on fertility.","authors":"Nikita K Patel, Alice Rhoton-Vlasak, Sungyoon Jung, Amelia M Schaub","doi":"10.1016/j.reprotox.2026.109384","DOIUrl":"10.1016/j.reprotox.2026.109384","url":null,"abstract":"<p><strong>Objective: </strong>To synthesize studies that identify and characterize microplastics (MPs) and nanoplastics (NPs) in human reproductive tissues, as well as their potential effect on ovarian reserve markers and sperm quality.</p><p><strong>Evidence review: </strong>A search of PubMed and Embase was performed to include any publications prior to September 4th, 2025, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.</p><p><strong>Results: </strong>Forty-one studies were included. Seven studies analyzed female tissues (follicular fluid and granulosa cells), nine studies examined male reproductive tissues (testis, epididymis, and semen), one study included tissues from males and females, and 24 investigated placental tissues. MPs and NPs were found to accumulate in follicular fluid, testis, epididymis, semen, and placenta. Preparation and detection methodology varied between the included studies. The exposure of MPs and NPs to human reproductive tissues was associated with metabolic dysfunction, an activation of oxidative stress pathways, and a shift toward apoptosis. While multiple studies found associations between MPs or NPs exposure and poor sperm motility, findings on associations between plastic particle presence and ovarian reserve markers or reproductive outcomes were inconsistent.</p><p><strong>Conclusion: </strong>The findings of this review show that MPs and NPs accumulate in human reproductive tissues and may induce cellular dysfunction. Additional investigations into the impact of MPs and NPs on ovarian reserve markers and reproductive outcomes are needed to better understand the potential impacts of plastic particle exposure on reproductive health.</p>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":" ","pages":"109384"},"PeriodicalIF":3.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207566","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 Phthalates with miR-3651, ATP6AP2, and SEC63 Dysregulation in Missed Abortion: Clinical and In Vitro Evidence.","authors":"Liujuan Ou, Wanhui Li, Ranran Zhao, Junshang Wen, Tierong Liao, Huishen Huang, Jun Liang, Yuxian He, Shimeng Huang, Xiaoqiang Qiu, Caizhu Wang, Dongping Huang","doi":"10.1016/j.reprotox.2026.109381","DOIUrl":"https://doi.org/10.1016/j.reprotox.2026.109381","url":null,"abstract":"<p><strong>Background: </strong>Missed abortion (MA) is a major pregnancy complication. Although phthalates (PAEs) are recognized reproductive toxicants and miR-3651 has been linked to embryogenesis, the interplay between them in the pathogenesis of MA remains unknown.</p><p><strong>Methods: </strong>The villous tissues were collected from 50 MA patients and 50 women undergoing elective termination. PAE exposure levels and the expression of miR-3651, ATP6AP2 and SEC63 were quantified. An in vitro PAEs exposure model was established in HTR-8/SVneo cells, and the expression of miR-3651, its target genes and related cytokines was measured.</p><p><strong>Results: </strong>In the MA group, miR-3651 was upregulated while ATP6AP2 and SEC63 were downregulated, accompanied by higher butyl benzyl phthalate (BBP) exposure (all p<0.05). LgBBP was significantly associated with MA (OR=4.434; 95% CI: 1.772, 11.094; p=0.001; q=0.019), whereas ATP6AP2 showed only a borderline inverse association (OR=0.354; p=0.051). LgMEHP (mono(2-ethylhexyl) phthalate) showed a nominal positive association with miR-3651 (β=0.610; 95% CI: 0.090, 1.129; p=0.022; q=0.110). Exploratory quantile g-computation (qgcomp) weights showed LgMEHP (43.36% of positive weights) and LgBBP (31.74% of negative weights) as the largest weight components for miR-3651 and ATP6AP2, respectively. In vitro, BBP and MEHP increased miR-3651 but decreased ATP6AP2 and SEC63 (p<0.05). Overexpression of miR-3651 downregulated PLGF and VEGF-A while upregulating IL-6, IL-17 and IFN-γ. Additionally, both BBP and MEHP reduced VEGF-A levels, while MEHP increased IL-6 levels (p < 0.05).</p><p><strong>Conclusion: </strong>This study shows that phthalate exposure is associated with miR-3651 upregulation and downregulation of ATP6AP2 and SEC63 in MA.</p>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":" ","pages":"109381"},"PeriodicalIF":3.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184104","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":"Corrigendum to \"Subtle morphological and molecular responses to low-dose diethylstilbestrol in the developing rat penis\" [Reprod. Toxicol. 140 (2026) 109149].","authors":"Emilie Elmelund, Marie Berg, Mikael Pedersen, Terje Svingen, Monica K Draskau","doi":"10.1016/j.reprotox.2026.109373","DOIUrl":"10.1016/j.reprotox.2026.109373","url":null,"abstract":"","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":" ","pages":"109373"},"PeriodicalIF":3.4,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149114511","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":"A Comprehensive Meta-Analysis on the Impact of airborne Particulate Matter on Trophoblast Cell Function In Vitro.","authors":"Jayabharthi Thirumalazhagan, Shivadas Sivasubramaniam, Vadivel Parthsarathy","doi":"10.1016/j.reprotox.2026.109364","DOIUrl":"https://doi.org/10.1016/j.reprotox.2026.109364","url":null,"abstract":"<p><p>Environmental particulate matter pollution is commonly associated with adverse pregnancy outcome, and impaired trophoblast development and function; however, the underlying biological mechanisms remain poorly understood. This meta-analysis aims to investigate the detrimental effects of particulate matter on cell viability, gene and protein expression pathways in trophoblast cells in vitro by systematically searching Google Scholar, PubMed, CENTRAL, Embase, CINAHL, MEDLINE for articles published up to September 2025. Pooled relative risks (RR) with 95% confidence intervals (CIs) were calculated to evaluate the gene and protein expression on exposure to PM2.5. Of 1506 records screened, 12 studies were selected based on the inclusion criteria. Results showed PM2.5 reduces cell viability collectively by 20.68%, disrupts steroidogenic enzymes (CYP11A1, 3β-HSD1, FDXR) separates hCG production from progesterone synthesis, further exacerbating inflammatory signalling. PM2.5 induces oxidative stress that further causes DNA damage, activating ATR-mediated p53-independent apoptosis. Angiogenic signalling through VEGF-VEGFR2-MEK-ERK-mTOR is supressed due to PM2.5 exposure. Matrix remodelling is also impaired due to the dominant TIMP expression, RhoA dysregulation, and Collagen I loss by collectively reducing migration, and invasive capability of the trophoblast cells. Overall, this meta-analysis underscores the underlying mechanisms by which PM2.5 consistently impairs trophoblast function and contributes to placental dysfunction.</p>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":" ","pages":"109364"},"PeriodicalIF":3.4,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025987","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":"Expression of concern: \"Maternal exposure to PM2.5 and its association with adverse pregnancy and birth outcomes: A prospective cohort study\" [Reprod. Toxicol. 140 (2026), 109127].","authors":"","doi":"10.1016/j.reprotox.2026.109335","DOIUrl":"10.1016/j.reprotox.2026.109335","url":null,"abstract":"","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":" ","pages":"109335"},"PeriodicalIF":3.4,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149076032","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":"Long-term and low-dose exposure to TDCPP reduces reproductive capacity by enhancing germline apoptosis associated with activation of DNA damage in Caenorhabditis elegans","authors":"Shudan Zheng ,&nbsp;Shangjin Li ,&nbsp;Bing Zhang,&nbsp;Shaojie Zhao","doi":"10.1016/j.reprotox.2026.109269","DOIUrl":"10.1016/j.reprotox.2026.109269","url":null,"abstract":"<div><div>Tris (1,3-dichloro-2-propyl) phosphate (TDCPP) arouses increasing attention, which probably poses exposure risks to human reproductive health because it is widely used and distributed. Nonetheless, its toxicities to reproductive system remain largely unknown. With <em>Caenorhabditis elegans</em> being the animal model, this study explored reproductive toxicities induced by TDCPP following long-time and low-dose exposure as well as its associated mechanism. According to our findings, brood size and the hatched egg number markedly decreased, meanwhile, relative area and length of gonad arm markedly declined after 0.1-10<!--> <!-->μg/L TDCPP exposure. Additionally, 0.1-10<!--> <!-->μg/L TDCPP exposure promoted germline apoptosis, down-regulated <em>ced-9</em> whereas up-regulated <em>ced-3</em>, <em>ced-4</em>, as well as <em>egl-1</em> levels; additionally, it aggravated germline DNA damage, accompanied by up-regulated <em>clk-2</em>, <em>cep-1</em>, and <em>hus-1</em> levels. Finally, computational toxicology, including molecular docking and molecular dynamics simulations, showed that TDCPP can effectively embed into the active pockets of CLK-2 and HUS-1 proteins governing DNA damage through interactions such as hydrogen bonds, thereby enhancing the local stability of protein conformation. Consequently, this study illustrated the reproductive toxicities of TDCPP at environmentally relevant concentrations through promoting DNA damage-related germline apoptosis within organisms.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"144 ","pages":"Article 109269"},"PeriodicalIF":2.8,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148056366","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":"Antipsychotic aripiprazole affects the sexual behavior and biochemical parameters of female Wistar rats","authors":"Aline Gabrielle Gomes da Silva ,&nbsp;Artemia Kelly Holanda Pereira ,&nbsp;Ana Beatriz Silva Angelo ,&nbsp;Caio César Araújo dos Santos ,&nbsp;Renata Gleysiane de Sousa Felix ,&nbsp;Maria Joana Nogueira de Moura ,&nbsp;Lícia Gabrielle Gomes de Oliveira ,&nbsp;Michelly Fernandes de Macedo ,&nbsp;Cibele dos Santos Borges","doi":"10.1016/j.reprotox.2026.109212","DOIUrl":"10.1016/j.reprotox.2026.109212","url":null,"abstract":"<div><div>Aripiprazole is a drug that modulates both the dopaminergic and serotonergic systems. It is currently widely used in the treatment of schizophrenia and mental disorders due to its stabilizing effect on the dopaminergic system. Studies on psychotropic drugs have demonstrated negative effects on hormonal regulation and sexual behavior as a consequence of their mechanism of action; however, the potential genotoxic effects of aripiprazole have not yet been fully clarified. Given the limited number of studies on the changes that this drug can cause in the reproductive system, the present study aimed to evaluate the impacts of aripiprazole on fertility and female sexual behavior, focusing on metabolic and endocrine-reproductive responses through biochemical and toxicological parameters related to reproduction. For this purpose, adult rats were divided into four experimental groups and subjected to different doses of aripiprazole (0, 0.3, 3.0, and 6.0 mg/kg), diluted in the vehicle (DMSO and saline) by gavage for 21 days. Estrous cyclicity was monitored, and reproductive and biochemical parameters were evaluated at the end of treatment. The results showed that there was no increase in body weight and that the data, in general, did not follow the monotonic dose-response curve. Biochemical changes in creatinine, albumin, and triglycerides were observed, in addition to adverse effects on cyclicity and sexual behavior. Thus, aripiprazole at doses of 0.3 and 6.0 mg/kg in this experimental model may cause toxic effects on the endocrine-reproductive system of fertile rats.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"142 ","pages":"Article 109212"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147388302","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}