Reproductive toxicology最新文献

{"title":"Protective effect of granulocyte colony stimulating factor on cyclophosphamide-induced prostate injury in rats.","authors":"Yuya Meng, Qian Ma, Yu Guo, Huanhuan Li, Xinxin Li, Shusong Wang, Jing Ma, Yanqing Tie","doi":"10.1016/j.reprotox.2026.109260","DOIUrl":"https://doi.org/10.1016/j.reprotox.2026.109260","url":null,"abstract":"<p><p>Cyclophosphamide (CPA) is a commonly used chemotherapeutic agent whose metabolites readily accumulate in male reproductive organs such as the testes and epididymis, exhibiting reproductive toxicity. Granulocyte colony-stimulating factor (G-CSF) possesses anti-inflammatory and antioxidant effects, but its protective mechanism against CPA-induced prostate injury remains unclear. This study aimed to investigate the protective effect of G-CSF against CPA-induced prostate injury in rats. Thirty SPF male Sprague-Dawley (SD) rats were randomly divided into a control group (C group), a CPA model group (M group), and a CPA+G-CSF group (G-CSF group). The M and G-CSF groups received intraperitoneal injections of cyclophosphamide (30mg/kg/d) for 5 consecutive days, while the C group received an equal volume of saline. Starting on the first day after the model was established, the G-CSF group began receiving G-CSF solution via subcutaneous injection at a dose of 50μg/kg body weight, three times a week for 5 consecutive weeks. Groups C and M received equivalent volumes of saline via subcutaneous injection. Serum and dorsal prostate tissue were collected for analysis after the final dose. Results: Rats in Group M exhibited reduced body weight, prostate weight, citric acid (CA) content, and acid phosphatase (ACP) activity. Hematoxylin and eosin (HE) staining revealed papillary hyperplasia with leukocyte infiltration. Elevated levels of interleukin-1β (IL-1β), IL-18, and C-reactive protein (CRP) increased, malondialdehyde (MDA) levels rose, superoxide dismutase (SOD) decreased, ZnT9 expression declined, and NF-κB nuclear translocation increased. G-CSF significantly reversed these pathological alterations. G-CSF alleviates CPA-induced prostate injury by improving zinc homeostasis through ZnT9 upregulation and suppressing NF-κB-mediated inflammation and oxidative stress, offering a novel therapeutic strategy for its prevention and treatment.</p>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":" ","pages":"109260"},"PeriodicalIF":2.8,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857044","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 \"Relationship of parental phthalate exposure with fetal growth and placental development at birth\" [Reprod. Toxicol. 137 (2025) 109025].","authors":"Hye Jin Chang, Yoon Hee Cho, Yeong Sook Yoon, Younglim Kho, Je Yeon Lee, Dong Won Hwang, Jung Yeol Han, Jisun Lee, Young Ah Kim","doi":"10.1016/j.reprotox.2026.109255","DOIUrl":"https://doi.org/10.1016/j.reprotox.2026.109255","url":null,"abstract":"","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":" ","pages":"109255"},"PeriodicalIF":2.8,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842303","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}

{"title":"Effects of bisphenol A and bisphenol S on human fallopian tube contractions: An in vitro and in silico study","authors":"Richa Singh ,&nbsp;Parul Sharma ,&nbsp;Sakshi Agarwal ,&nbsp;Shristi Modanwal ,&nbsp;Sushmitha Paulraj ,&nbsp;Sanjeev Kumar Mahto","doi":"10.1016/j.reprotox.2026.109211","DOIUrl":"10.1016/j.reprotox.2026.109211","url":null,"abstract":"<div><div>Bisphenol A (BPA), a widely used industrial compound, and its structural analogue Bisphenol S (BPS) are known to exert reproductive toxicity. However, their direct impact on human fallopian tube contractility remains unexplored. This study aimed to investigate the effects of BPA and BPS on spontaneous smooth muscle contractions of the human fallopian tube. Fallopian tube samples from the proliferative phase were used for in vitro contractility assays. The effects of BPA and BPS (1–20 µM) on maximum contractile strength (MCS), basal tone (BT), and contraction frequency (CF) were recorded and analyzed using ANOVA. Cytotoxicity of both compounds was assessed in MCF-7 cells using the MTT assay. Molecular docking examined BPA and BPS binding affinities to key receptors. Both BPA and BPS significantly reduced contractile activity in a concentration-dependent manner (p &lt; 0.001), with BPA exhibiting a stronger inhibitory effect than BPS. MTT assays demonstrated a significant dose- and time-dependent decrease in cell viability for both compounds. Molecular docking indicated comparable binding affinities of BPA and BPS toward estrogen, progesterone, oxytocin, prostaglandin, and calcium channel receptors. BPA and BPS impair human fallopian tube contractility and exhibit cytotoxicity. These findings highlight potential reproductive risks associated with exposure to bisphenol compounds and underscore the need for subsequent extensive studies.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"142 ","pages":"Article 109211"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147388303","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":"Identifying and reporting dystocia in laboratory rodents","authors":"Paul Barrow ,&nbsp;Prägati S. Coder ,&nbsp;Rashin Ghaffari ,&nbsp;Leah Zorrilla ,&nbsp;Christopher J. Bowman ,&nbsp;Curtis E. Grace ,&nbsp;Jason Manton ,&nbsp;Alan Hoberman ,&nbsp;Narinder Barraclough ,&nbsp;Isabelle Leconte ,&nbsp;Nicola Powles-Glover ,&nbsp;Connie Chen ,&nbsp;Shermaine Mitchell-Ryan","doi":"10.1016/j.reprotox.2026.109206","DOIUrl":"10.1016/j.reprotox.2026.109206","url":null,"abstract":"<div><div>Dystocia (prolonged, difficult, and/or delayed parturition) results from a variety of potential clinical conditions including uterine inertia, hormonal imbalances, oversized fetuses, abnormal orientation of fetuses in the birth canal, etc. In the laboratory, dystocia frequently results in euthanasia. In 2020, the Health and Environmental Sciences Institute’s Developmental and Reproductive Toxicology committee formed a working group to discuss anecdotal reports of increased incidence of dystocia amongst laboratory rodents. Based on an initial survey completed by contributing laboratories, it became apparent that there is significant disparity in how various laboratories define, record, report, and interpret dystocia in laboratory animals. This report highlights the key findings from a survey of performing laboratories conducted by this working group and proposes best practices and recommendations for the monitoring and recording of parturition and dystocia in reproductive toxicity studies in rodents. Implementing consistent definitions, observation strategies, and documentation standards will strengthen data comparability and enhance the scientific foundation on which regulatory decisions are made. Furthermore, consistent reporting of dystocia across industry laboratories will improve the transparency and reliability of evidence used in hazard identification and risk assessment and thereby help reduce discrepancies in regulatory outcomes and facilitate regulatory decision-making for chemicals, plant protection products, biocides, and pharmaceuticals.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"142 ","pages":"Article 109206"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147326976","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 5-alpha Reductase Inhibitors on Male Reproductive Health: A Review of Finasteride and Dutasteride.","authors":"Tania Quintero, Ben Gratz, Luke Pepperney, Jake Rosenstadt, G Ian Gallicano","doi":"10.1016/j.reprotox.2026.109257","DOIUrl":"https://doi.org/10.1016/j.reprotox.2026.109257","url":null,"abstract":"<p><p>Androgenic alopecia (AGA), commonly known as male pattern baldness (MPB), affects a significant portion of the population, with impacts on self-esteem and quality of life. 5-alpha reductase inhibitors, including finasteride and dutasteride, are widely used treatments that increase hair density by reducing dihydrotestosterone levels. However, their effects on reproductive health remain a concern, particularly in men of reproductive age. This narrative review synthesizes current clinical and experimental evidence on the reproductive effects of 5-alpha reductase inhibitors. Relevant studies were identified through a review of published literature, including randomized controlled trials, observational studies, and mechanistic investigations. Outcomes of interest included sperm parameters, hormonal profiles, sexual function, and potential long-term reproductive effects. Across studies, finasteride and dutasteride were associated with reductions in sperm count (34% with finasteride, 29% with dutasteride), sperm concentration, and motility. Hormonal alterations included, increased testosterone levels, and variable changes in dihydrotestosterone, estradiol, progesterone and androstenedione levels. Findings related to sexual dysfunction were variable, with some demonstrating persistent decreased libido, erectile dysfunction, and reduced penile sensitivity, months to years after discontinuation. Mechanistic studies in rodents revealed significant reductions in the expression of genes critical to spermatogenesis (Dazl, Prm2, Sycp3, Tsga10) and alterations in penile tissue contractility and nitric oxide synthase signaling, providing potential explanations for these reproductive effects. Overall, while 5-alpha reductase inhibitors are effective treatments for AGA, they may adversely affect reproductive parameters in a subset of patients. While current evidence focuses primarily on single drug regimens, the growing use of combination therapies targeting multiple 5-alpha reductase isotypes raises the potential for additive or synergistic reproductive effects. Given the variability in outcomes and limited long-term data, further research is needed to better characterize these risks, particularly in younger populations and with combination therapies.</p>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":" ","pages":"109257"},"PeriodicalIF":2.8,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147820232","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":"Protective Effects of p-Coumaric Acid Against Paclitaxel-Induced Testicular Damage: Role of Oxidative Stress, Inflammation, Apoptosis, and Autophagy.","authors":"Samet Tekin, Merve Bolat, İsmail Bolat, Ömercan Alat, Burak Batuhan Laçin, Burak Çinar, Tuba Karaarslan, Serkan Ali Akarsu, Emin Şengül, Dursunali Çinar, Fikret Çelebi","doi":"10.1016/j.reprotox.2026.109235","DOIUrl":"https://doi.org/10.1016/j.reprotox.2026.109235","url":null,"abstract":"<p><p>Paclitaxel (PTX), despite its widespread antineoplastic use, induces severe reproductive toxicity by triggering oxidative stress, inflammation, and apoptosis in testicular tissue. In this study, the effects of p-Coumaric Acid (PCA) on oxidative stress, inflammation, apoptosis, and hormonal balance were evaluated at histopathological, biochemical, and molecular levels in a rat model of PTX-induced testicular injury. PTX increases reactive oxygen species (ROS) production and suppresses antioxidant defenses, thereby elevating lipid peroxidation; enhances nuclear factor kappa-B (NF-κB) and Toll-like receptor 4 (TLR4)-mediated pro-inflammatory cytokines interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α); and reduces interleukin-10 (IL-10) levels. The accompanying increase in Bcl-2-associated X protein (Bax) and Caspase-3, along with a decrease in B-cell lymphoma-2 (Bcl-2), leads to germ cell loss and impaired spermatogenesis. In our study, PCA markedly attenuated these PTX-induced oxidative, inflammatory, and apoptotic processes. PCA treatment reduced malondialdehyde (MDA) levels, enhanced superoxide dismutase (SOD) and glutathione (GSH) activities, normalized cytokine balance, and preserved seminiferous tubule integrity. Moreover, PCA improved sperm density and motility, decreased abnormal morphology, and partially restored reduced testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels. Overall, the findings indicate that PCA may serve as a potential therapeutic agent against PTX-induced testicular damage through its strong antioxidant and cytoprotective effects.</p>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":" ","pages":"109235"},"PeriodicalIF":2.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147616605","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":"Co-exposure to arsenic and nickel alters the morphology and oxidative status of the ventral prostate of Wistar rats","authors":"João Victor Leles Faria ,&nbsp;Luiz Otávio Guimarães-Ervilha ,&nbsp;Thainá Iasbik-Lima ,&nbsp;John Lennon de Paiva Coimbra ,&nbsp;Tungstênio Lima de Souza ,&nbsp;Guilherme Mattos Jardim Costa ,&nbsp;Renê Chagas da Silva ,&nbsp;Mônica Morais Santos ,&nbsp;Mariana Machado-Neves","doi":"10.1016/j.reprotox.2026.109182","DOIUrl":"10.1016/j.reprotox.2026.109182","url":null,"abstract":"<div><div>Arsenic and nickel are toxic chemicals with the capability to accumulate in tissues and cause various health problems, including reproductive disorders. There is no information on whether the mixture of those two chemicals may intensify prostate damage in rats. Therefore, this study aimed to verify the effects of arsenic and nickel exposure on the rat ventral prostate, using histological, biochemical, molecular, and hormonal approaches. Forty Wistar rats were divided into four groups (<em>n</em> = 10/group). Control rats received saline solution in drinking water, whereas rats from the exposed groups ingested arsenic (1 mg L⁻¹), nickel (7 mg L⁻¹), and the two metals simultaneously at the same concentrations. After 70 days of treatment, the ventral prostate was collected, dissected, and processed for microscopic and biochemical analyses. Arsenic-exposed rats showed high estradiol and protein carbonyl levels, arsenic and iron content, and low percentage of collagen fiber I in their ventral prostate. Nickel-exposed rats presented high nickel and iron content, cell and cytoplasmic area, epithelial height, and low zinc proportion. Co-exposed rats exhibited most of the alterations observed here, involving oxidative imbalance, protein oxidation, low collagen fiber content, and high mast cell count. The co-exposure induced inflammatory foci, hyperplasia, and glandular atrophy in the ventral prostate. The <em>in silico</em> analysis revealed metal interactions with cancer, cell cycle, and oxidative stress proteins. Summarizing, co-exposure to arsenic and nickel intensified prostate damage, evidencing an oxidative process and tissue damage that confirms the prostate’s sensitiveness to metal mixture after a subchronic exposure.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"141 ","pages":"Article 109182"},"PeriodicalIF":2.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146135691","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":"Early-life BPS exposure induces reproductive toxicity in offspring mice via ferroptosis","authors":"Yan Su ,&nbsp;Xinxin Guo ,&nbsp;Nuo Xu ,&nbsp;Mengfen Pan ,&nbsp;Kaixing Lin ,&nbsp;Huaicai Zeng ,&nbsp;Qingzhi He","doi":"10.1016/j.reprotox.2026.109175","DOIUrl":"10.1016/j.reprotox.2026.109175","url":null,"abstract":"<div><div>Bisphenol S (BPS), a widely utilized environmental endocrine disruptor, poses significant risks to environmental pollution and human health. While the reproductive toxicity of BPS is recognized, its transgenerational consequences, particularly from early-life exposure, remain poorly defined. In this study, we established a mouse model of early-life BPS exposure to assess its effects on male reproductive development in offspring. Our findings demonstrate that early-life BPS (0.2, 2, 20 mg/L) exposure impairs testicular architecture, diminishes sperm quantity, elevates sperm morphological abnormalities, and dysregulates the expression of CYP11A1, CYP17A1, STAR, and HSD17B3. These changes collectively result in suppressed testosterone production and disrupted spermatogenesis in offspring mice. Additionally, early-life BPS exposure triggered oxidative stress, elevating malondialdehyde levels while reducing superoxide dismutase and glutathione. In offspring mice, BPS induced testicular iron accumulation and mitochondrial damage. This was accompanied by elevated expression of ACSL4 and TFR1, alongside reduced levels of GPX4 and SLC7A11. In TM3 Leydig cells, Fer-1 (1 µM) effectively restored BPS (80 µM)-induced testosterone deficiency and normalized the expression of key ferroptosis-related proteins. Collectively, this study establishes ferroptosis as a critical mechanism in the transgenerational male reproductive damage induced by BPS, thereby providing novel insights into the toxicological effects of environmental endocrine disruptors.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"140 ","pages":"Article 109175"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077531","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":"Uterine artery transcriptomic signatures of e-cigarette aerosol exposure in pregnancy","authors":"Alexander L. Carabulea ,&nbsp;Vishal D. Naik ,&nbsp;Joseph D. Janeski ,&nbsp;Hong Jiang ,&nbsp;Saravanan Venkatachalam ,&nbsp;Jayanth Ramadoss","doi":"10.1016/j.reprotox.2025.109133","DOIUrl":"10.1016/j.reprotox.2025.109133","url":null,"abstract":"<div><div>Electronic cigarette (e-cig) use among U.S. adults has shifted notably, with increased adoption among younger adults and middle-aged individuals transitioning from traditional cigarettes. We herein investigated the impact of gestational e-cig aerosol exposure on uterine artery (UA) transcriptome. Timed-pregnant Sprague-Dawley rats were randomly assigned to either the pair-fed Control or the E-cig group before initiation of vaping (4 s e-cig vapor every 2 min, two episodes of 1.5 h each; gestational day (GD) 5 until GD 20). Maternal weight and placental efficiency were not altered, whereas there was a significant deficit in fetal body weight and crown-rump length in the E-cig group on GD 21. Twenty three genes were significantly upregulated, while 40 genes were downregulated in the uterine artery of the E-cig group when compared with the Control group uterine artery. The top significantly downregulated genes in the uterine artery include genes involved in extracellular matrix and Wnt signaling regulation (Smoc2, Gpc3, Frzb, Sfrp2), immune and inflammatory response (C1qtTNF3, Tmem82, Clec21), muscle contraction (Actc1) and cell migration ( Gas2l3, Ret, Robo2). Top upregulated genes in the uterine artery (Vsig4, Agt, Cntn2, Kcnk5, Fhad1, Fgf13, Ctxn1, Prg4, and Pln) included genes involved in immune response and regulation (Vsig4, Kcnk5), and uterine artery vasodilation (Agt). Significant differences between the Control and E-cig groups were validated using Principal Component Analysis (PCA) and k-means clustering. These findings reveal how e-cig aerosol exposure during pregnancy may disrupt key biological processes in the uterine artery that delivers O₂ and nutrients to the fetoplacental compartment.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"140 ","pages":"Article 109133"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145692209","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}