Reproductive toxicology最新文献

{"title":"Long term exposure to benzo[b]fluoranthene does not induce mutations in Mutamouse male germ cells","authors":"Madison T. Stewart ,&nbsp;Gu Zhou ,&nbsp;Danielle P.M. LeBlanc ,&nbsp;Annette E. Dodge ,&nbsp;Matthew J. Meier ,&nbsp;Andrew Williams ,&nbsp;Alexandra S. Long ,&nbsp;Paul A. White ,&nbsp;Carole L. Yauk ,&nbsp;Francesco Marchetti","doi":"10.1016/j.reprotox.2025.108985","DOIUrl":"10.1016/j.reprotox.2025.108985","url":null,"abstract":"<div><div>Germ cell mutations can be inherited and lead to genetic disorders in the offspring. Thus, it is critical to identify environmental exposures that impact the germline. Polycyclic aromatic hydrocarbons (PAHs) are widespread combustion by-products found in food, tobacco smoke, and urban air. Benzo[<em>b</em>]fluoranthene (BbF) is a PAH that is classified as a possible human carcinogen. Studies using the transgenic mouse <em>lacZ</em> assay and duplex sequencing (DS), an error-corrected sequencing technology, have demonstrated that BbF robustly induces mutations in somatic tissues. However, the mutagenic effects of BbF on germ cells are unknown. We investigated whether long-term exposure to BbF induces mutations in male germ cells. Adult MutaMouse males were orally exposed to BbF in olive oil at doses of 0, 3.25, 6.25, 12.5, 25, or 50 mg/kg body weight per day (BW/day) for 90 days, or to 0, 1.56, 3.125, 6.25, 12.5, or 25 mg/kg BW/day for 180 days. Mutant frequencies were determined using the <em>lacZ</em> assay (n = 8 per group). Control and high dose groups at each time point were then sequenced to detect mutations using DS (n = 6 per group). Neither method detected significant increases in mutations following BbF exposure. Similarly, there was no increase in C:G &gt; A:T transversions at either time point, the main mutation subtype induced by BbF in somatic tissues. These results suggest that BbF or its active metabolites are not present in germ cells at amounts sufficient to cause mutations, and/or DNA damage repair mechanisms in germ cells effectively repair BbF-induced damage.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 108985"},"PeriodicalIF":3.3,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144589192","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":"Perfluorooctanoic acid (PFOA) induces apoptosis by disrupting mitochondrial function via the SIRT1/FOXO1-SOD2 pathway in human granulosa cells: Implications for PCOS","authors":"Yumeng Ren ,&nbsp;Yun Liang ,&nbsp;Shuyi Zhang ,&nbsp;Fumei Gao","doi":"10.1016/j.reprotox.2025.108986","DOIUrl":"10.1016/j.reprotox.2025.108986","url":null,"abstract":"<div><div>Perfluorooctanoic acid (PFOA), a widely used perfluoroalkyl substance (PFAS), has been associated with adverse reproductive health outcomes, including polycystic ovary syndrome (PCOS). However, the molecular mechanisms remain poorly understood. In this study, we explored the effects of PFOA exposure on granulosa cell apoptosis, a key contributor to PCOS pathogenesis. Human ovarian granulosa-like tumor cell line (KGN) was exposed to PFOA (0–100 μM), resulting in a significant increase in cell apoptosis and impaired mitochondrial function, as evidenced by elevated reactive oxygen species (ROS) levels, decreased mitochondrial membrane potential (MMP), and reduced adenosine triphosphate (ATP) production. Mechanistically, PFOA exposure led to the downregulation of the SIRT1/FOXO1–SOD2 signaling pathway. Notably, activation of this pathway via pharmacological agonizts attenuated PFOA-induced apoptosis and restore mitochondrial function. These findings demonstrate that PFOA exposure can induce granulosa cell apoptosis by downregulating the SIRT1/FOXO1-SOD2 pathway, leading to impaired mitochondrial antioxidant capacity. This study provides novel mechanistic insights into the reproductive toxicity of PFOA and its potential role in the etiology of PCOS.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 108986"},"PeriodicalIF":3.3,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144589265","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":"Mitigation of hyperglycemia-induced leydig cell dysfunction by gut derived indol 3- propionic acid: Targeting apoptosis, endoplasmic reticulum stress response and steroidogenesis","authors":"Cyrus Jalili ,&nbsp;Touraj Zamir Nasta ,&nbsp;Fatemeh Makalani ,&nbsp;Elahe Davoodi ,&nbsp;Mohammad Reza Tabandeh","doi":"10.1016/j.reprotox.2025.108987","DOIUrl":"10.1016/j.reprotox.2025.108987","url":null,"abstract":"<div><div>Indole-3-propionic acid (IPA), a gut-derived compound, has demonstrated promising antidiabetic, anti-inflammatory, and antioxidant properties. However, its potential role in mitigating male reproductive dysfunction, particularly in the context of hyperglycemia, remains poorly understood. This study aims to investigate the effect of IPA on the Leydig cell dysfunction under hyperglycemic (HG) condition. TM3 mouse Leydig cells were cultured in DMEM/F12 medium containing low (5 mM) and high (30 mM) glucose concentrations in the presence of 10 and 20 µM of IPA for 24 h. Cell viability was assessed by MTT method. The expression of steroidogenesis associated genes 3β-hydroxysteroid dehydrogenase; (<em>Hsd3b1</em>), follicle-stimulating hormone receptor (<em>Fshr</em>), cytochrome P450 side-chain cleavage enzyme(<em>P450scc</em>), and steroidogenic acute regulatory protein (<em>Star</em>)) was evaluated by qRT-PCR analysis.The protein levels of endoplasmic reticulum stress (ERS) related proteins (ATF6, IRE1, GRP78, and CHOP) were determined by Western blot analysis. Testosterone levels were measured by ELISA method. Cell apoptosis was determined using Anexinv/PI flow cytometery analysis. Hyperglycemia decreased cell viability, testosterone production, and the expression of <em>Hsd3b1</em>, <em>Fshr</em>, <em>P450scc</em>, and <em>Star</em> in TM3 cells. Under hyperglycemic conditions, TM3 cells exhibited increased apoptosis and elevated expression of ATF6, PERK, GRP78, and CHOP proteins. IPA, particularly at a dose of 20 µM, increased cell viability and enhanced the expression of steroidogenesis-related genes under HG conditions. Additionally, IPA at doses of 10 and 20 µM attenuated apoptosis and reduced the expression of ERS proteins under HG. The potential therapeutic role of IPA in alleviating the complications caused by hyperglycemia in Leydig cells makes it a promising candidate in the treatment of male reproductive dysfunction associated with diabetes.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 108987"},"PeriodicalIF":3.3,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144589268","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":"Mendelian randomization analysis reveals causal associations between autoimmune diseases and female infertility risk","authors":"Jinyuan Wang ,&nbsp;Haojun Long ,&nbsp;Mingxuan Su ,&nbsp;Yichang Cao ,&nbsp;Runtang Zhou ,&nbsp;Xiang Li ,&nbsp;Jiangming Li ,&nbsp;Yuxia Tang ,&nbsp;Jiayi Tang ,&nbsp;Simin Wang ,&nbsp;Linyue Tang ,&nbsp;Ruxin Chen ,&nbsp;Danqi Deng ,&nbsp;Li Tang","doi":"10.1016/j.reprotox.2025.108984","DOIUrl":"10.1016/j.reprotox.2025.108984","url":null,"abstract":"<div><h3>Background</h3><div>Infertility is viewed as a significant social challenge globally. Numerous observational studies have documented the link between autoimmune diseases (ADs) and female infertility, yet the underlying cause remained unclear. The primary objective of this study was to ascertain the causal connection between ADs and female infertility.</div></div><div><h3>Method</h3><div>We evaluated summary statistics from genome-wide association studies (GWAS) for prevalent autoimmune diseases (systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes (T1DM), celiac disease (CeD), inflammatory bowel disease (IBD), ankylosing spondylitis (AS), Crohn's disease (CD), ulcerative colitis (UC), psoriasis and female infertility. Initial two-sample Mendelian randomization (MR) analyses was conducted to pinpoint causal autoimmune diseases associated with female infertility in the discovery and replication analysis.</div></div><div><h3>Results</h3><div>Our two-sample Mendelian randomization analysis, using data from the UK Biobank and FinnGen (or IIBDGC), provided evidence for a causal association between genetically predicted rheumatoid arthritis (RA), type 1 diabetes (T1DM), celiac disease (CeD), and ulcerative colitis (UC) and an increased risk of female infertility. These associations were observed across different sub-phenotypes of infertility.</div></div><div><h3>Conclusions</h3><div>This Mendelian randomization study, based on large-scale GWAS datasets, provides genetic evidence supporting a causal association between several autoimmune diseases and increased female infertility risk. These findings highlight the potential role of immune-mediated mechanisms in reproductive dysfunction and may inform future research into early interventions and fertility-preserving strategies in affected individuals.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 108984"},"PeriodicalIF":3.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565116","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 carbamazepine-exposure on rat epididymal sperm in parental (F0) and F1 generations","authors":"Marina Nunes ,&nbsp;Catarina Conrado de Britto ,&nbsp;Rafaela Doretto do Valle Freitas ,&nbsp;Amanda Seraphim Oliveira ,&nbsp;Leonardo Wensing Fischer ,&nbsp;Sandra Maria Miraglia ,&nbsp;Samara Urban de Oliva","doi":"10.1016/j.reprotox.2025.108981","DOIUrl":"10.1016/j.reprotox.2025.108981","url":null,"abstract":"<div><div>Carbamazepine (CBZ) is a medication used for neurological and psychiatric disorders treatment. Its potential side effects on male reproduction are a cause for concern. Alterations in sperm parameters and sex hormone levels have been reported during and after prolonged therapy with CBZ. However, alterations in sperm quality are not necessarily associated with a decrease in fertility, and may potentially lead to adverse effects on the offspring. The study aimed to evaluate the qualitative and quantitative parameters of epididymal sperm in CBZ-treated adult rats from pre-puberty to adulthood (F0 generation) and their potential impact on the spermatozoa of their offspring (F1 generation). Male rats were treated with CBZ (20 mg/Kg/day), administered by gavage, from pre-puberty (23 postnatal days - pnd) until adulthood (95pnd). The control group received olive oil (vehicle) following the same experimental procedure. At 95pnd, sperm qualitative and quantitative parameters were analyzed in the F0 and F1 generations. Measurements of testicular and epididymal malondialdehyde levels and plasma testosterone levels were also performed. Paternal chronic CBZ exposure (F0 generation) reduced sperm motility and viability, increased DNA fragmentation, and altered mitochondrial activity and acrosome integrity. Testosterone levels, testicular step 19 spermatid and daily sperm production also decreased. Significant increases in oxidative stress in the testis and epididymis were observed. These alterations also occurred in the F1 generation. The results suggest that prolonged paternal exposure to CBZ can cause sperm qualitative and quantitative alterations, decrease in testosterone levels, affecting intergenerationally the male reproductive health of offspring.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"136 ","pages":"Article 108981"},"PeriodicalIF":3.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144548606","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 polystyrene nanoplastics on the female reproductive system in mice: Implications for ovarian function and follicular development","authors":"Mahsa Gholiof ,&nbsp;Jocelyn M. Wessels ,&nbsp;Warren G. Foster ,&nbsp;Victoria Turpin ,&nbsp;Mathew Leonardi","doi":"10.1016/j.reprotox.2025.108983","DOIUrl":"10.1016/j.reprotox.2025.108983","url":null,"abstract":"<div><h3>Introduction</h3><div>Plastic pollution has led to widespread accumulation of microplastics (MPs) and nanoplastics (NPs), increasing human exposure via ingestion, inhalation, and dermal contact. While MPs have been linked to endocrine and reproductive toxicity, studies on NPs, especially their effects on female reproductive health, remain limited. Given their smaller size and greater bioavailability, NPs may cross biological barriers and accumulate in reproductive tissues. This study examines the effects of oral polystyrene nanoplastics (PS-NPs) on estrous cyclicity, follicle development, atresia, corpora lutea formation, and serum hormone levels in female mice.</div></div><div><h3>Materials and methods</h3><div>Female C57BL/6 mice were orally exposed to water (control) or PS-NPs (100 µg/L or 1000 µg/L) daily for 29 days. Vaginal lavage samples were collected during the last 15 days to monitor estrous cyclicity. At study completion, mice were euthanized, and blood and ovarian tissues were collected for analysis. Ovaries were processed for histological evaluation, and serum hormone levels were quantified using ELISA.</div></div><div><h3>Results</h3><div>PS-NPs exposure significantly increased estrous cycle length in the high-dose group compared to control (5.53 ± .80 days vs 4.70 ± 0.71 days, P = 0.02). Serum progesterone levels were significantly reduced in the high-dose group compared to control (mean difference = 1.64 pg/mL, standard error of difference (SED) = 0.64, P = 0.03). Antral follicle diameter decreased significantly in both exposure groups compared to control, with a more pronounced reduction at the higher dose (P = 0.001). Additionally, chronic PS-NPs exposure led to a significant decrease in corpora lutea density and a significant increase in atretic follicle density in the high exposure group compared to control (mean difference = 1.46, SED = 0.52, P = 0.02 &amp; mean difference = 3.01, SED = 0.95, P = 0.01 respectively).</div></div><div><h3>Conclusion</h3><div>Chronic PS-NPs exposure in female mice disrupted ovarian function as evidenced by a dose-dependent reduction in antral follicle size, decreased corpora lutea density, increased atretic follicle density, prolonged estrous cycles, and decreased serum progesterone levels, suggesting potential implications for anovulation, infertility, and other reproductive disorders. Future studies should further investigate the mechanisms underlying NPs-induced reproductive toxicity.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"136 ","pages":"Article 108983"},"PeriodicalIF":3.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144549336","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":"Deep RNA analyses for BeWo cells and placentae of HIV positive pregnant women treated with lopinavir/ritonavir","authors":"Shi Zou ,&nbsp;Wei Guo ,&nbsp;Miao Tan ,&nbsp;Xuechen Yu ,&nbsp;Jinli Liu ,&nbsp;Qian Du ,&nbsp;Yuting Tan ,&nbsp;Yingjie Wu ,&nbsp;Songjie Wu ,&nbsp;Yanan Zhu ,&nbsp;Yong Feng ,&nbsp;Ke Liang","doi":"10.1016/j.reprotox.2025.108980","DOIUrl":"10.1016/j.reprotox.2025.108980","url":null,"abstract":"<div><h3>Introduction</h3><div>Combination antiretroviral therapy (cART) based on protease inhibitor lopinavir /ritonavir (LPV/r) is the first-line regimen for HIV-infected pregnant women to prevent mother-to-child transmission (MTCT) in China. Studies have indicated a correlation between LPV/r and adverse pregnancy outcomes (APOs). However, a knowledge gap exists regarding the potential mechanisms.</div></div><div><h3>Methods</h3><div>In this study, the transcriptomics and proteomics analyses were performed to investigate the genes in BeWo cells and human placentae exposed to LPV/r. BeWo cells were treated with LPV/r with different concentrations for 24 h, then the mRNAs were sequenced. We also adopted proteomics sequencing between human placentae exposed to LPV/r and non-LPV/r based antiretroviral regimens. Flow cytometry analysis, real-time PCR and immunohistochemistry were performed to verified our sequencing results.</div></div><div><h3>Results</h3><div>A Total 800–4000 differentially expressed genes (DEGs) after LPV/r treatment in Bewo cells were identified compared to the vehicle control. There were 321 differentially expressed proteins (DEPs) in the LPV/r group of human placentae. Comprehensive analysis of the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms in transcriptomics and proteomics analyses demonstrated that LPV/r may result in APOs via active apoptosis, Endoplasmic reticulum (ER) stress, oxidative stress and lipid metabolism. Expression up-regulation of BAX (Bcl2 Associated X Protein), C-FOS (Cellular oncogene fos), P53 (Tumor suppressor protein p53) and down- regulation of MDM2 (Mouse double minute 2 homolog) by LPV/r may be the key genes for APOs.</div></div><div><h3>Conclusions</h3><div>Apoptosis by LPV/r may be the most important factor for APOs. The deep analysis provides important clues for understanding the mechanisms for the APOs were attributed to LPV/r.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"136 ","pages":"Article 108980"},"PeriodicalIF":3.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529475","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":"Cannabis sativa extract and fertility: Preclinical evaluation in male and female Wistar rats","authors":"Alana C. Costa ,&nbsp;Cícero A.C. Pereira ,&nbsp;Arquimedes Gasparotto Jr. ,&nbsp;Alana A.K. Garcia ,&nbsp;Emerson L.B. Lourenço ,&nbsp;Helena P.G. Joaquim","doi":"10.1016/j.reprotox.2025.108982","DOIUrl":"10.1016/j.reprotox.2025.108982","url":null,"abstract":"<div><div>Currently, there are reservations regarding the medicinal use of <em>Cannabis sativa</em> extract and its potential to impact fertility. Certain cannabinoids, such as Δ⁹-tetrahydrocanabinol (THC), can modulate both male and female sex hormones, potentially leading to alterations in fertilization viability. This study aims to evaluate the effects of standardized <em>Cannabis sativa</em> extract (CSE) and its respective placebos on fertility and early embryonic development in Wistar rats, including both male and female subjects. The animals were divided into 7 groups, each consisting of 20 animals, and different doses of a Cannabis sativa extract (160.32 mg/mL) were administered to assess fertility outcomes. Male and female fertility assessments were conducted according to the guidelines outlined in the \"Guide for the Conduct of Non-Clinical Toxicology and Pharmacological Safety Studies Required for Drug Development,\" including clinical exams, biochemical analyses, macroscopic evaluations, relative organ weight measurements, sperm production, and morphology assessments, as well as morphometric and histopathological analyses of the testes. The results indicated that none of the tested doses (0.28, 2.8, 28, or 56 mg/kg/bw) significantly affected sex hormone levels in either male or female rats. Additionally, no alterations were observed in male organ morphology and sperm characteristics. In female rats, fertility was unaffected, and blastocyst implantation was not impaired across all doses, even up to 7 days post-pregnancy confirmation. No direct toxic effects on the embryo were observed. In conclusion, treatment with <em>Cannabis sativa</em> extract did not result in any significant changes in fertility or pregnancy feasibility in either male or female rats.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"136 ","pages":"Article 108982"},"PeriodicalIF":3.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In utero benzene exposure in CD-1 mice results in increased fetal and placental size at gestational day 19, which is dependent upon intra-litter variables","authors":"Megan E. Cull ,&nbsp;Lauren T.L. Brown ,&nbsp;Perri M. Grant ,&nbsp;Lihua Xue ,&nbsp;Louise M. Winn","doi":"10.1016/j.reprotox.2025.108979","DOIUrl":"10.1016/j.reprotox.2025.108979","url":null,"abstract":"<div><div>Benzene is a common environmental pollutant and carcinogen. In a previous mouse study, we found that transplacental benzene exposure increased tumor incidence in offspring, with apparent sex differences. Mouse models are widely used in developmental toxicity studies; however, they are litter-bearing and show intra-litter variability. This study sought to determine if <em>in utero</em> benzene exposure affects fetal and placental growth with consideration for intra-litter variables. Pregnant CD-1 mice were exposed to corn oil (vehicle control) or 200 mg/kg benzene from gestational days (GD) 8–14 and sacrificed on GD 19. Fetal-placental units were grouped by exposure, sex, and uterine horn location. Fetus and placenta growth measurements were normalized to maternal weight gain and total live litter size or the number of live fetuses in the uterine horn. <em>In utero</em> benzene exposure did not affect fetal survival or the distribution of fetuses between sexes or uterine horns, but did significantly increase fetal and placental size, particularly in the left uterine horn. Both male and female fetuses showed increased weight, head-rump length, head circumference, and abdominal circumference, with the left horn most affected. Placental weight and diameter also increased, with larger placentas in the left horn. Fetal heart weight increased, especially in female fetuses. Placental efficiency was not significantly altered, though benzene-exposed females had higher efficiency than males. These findings suggest that benzene induces placental toxicity, leading to altered growth, and emphasize the need to account for intra-litter variability in xenobiotic-induced developmental toxicity studies.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"136 ","pages":"Article 108979"},"PeriodicalIF":3.3,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144491699","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":"Cannabinoid exposure does not alter estradiol biosynthesis in human KGN granulosa cells","authors":"Lanna Kadhim ,&nbsp;Seneca Paquette-Jager ,&nbsp;David A. Landry","doi":"10.1016/j.reprotox.2025.108978","DOIUrl":"10.1016/j.reprotox.2025.108978","url":null,"abstract":"<div><div>Steroidogenesis is essential for ovarian physiology and reproductive health. Regulated by hormonal signals, it is susceptible to external modulators, notably environmental exposures. As cannabis becomes more accessible globally, its use among women of reproductive age has increased, yet the implications for reproductive endocrinology remain poorly understood and contradictory. In this study, we investigated whether cannabinoids modulate basal or stimulated estradiol secretion in the human granulosa cell line KGN. To characterize the endocannabinoid system (ECS) in these cells, we performed a meta-analysis of publicly available RNA sequencing datasets, revealing expression of key ECS components. KGN cells were cultured with or without cannabinoids in the presence of protein kinase activators, PKA (FSK), PKB (SC79), and PKC (PMA). Following cannabinoid and kinase stimulations, the media were collected and analyzed for estradiol concentrations via ELISA. We observed no significant changes in basal or activated estradiol secretion in response to THC or CBD. These findings were supported by RT-qPCR analysis showing no alteration in the expression of <em>CYP19A1</em>, the gene encoding aromatase, which catalyzes the conversion of androgens to estrogens in granulosa cells. Although cannabinoids have been shown to influence sex hormones in vivo, our data suggest that these effects are not mediated at the granulosa cell level. This study contributes to a better understanding of how cannabinoids may interact with ovarian steroidogenesis and reproductive function.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"136 ","pages":"Article 108978"},"PeriodicalIF":3.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144365785","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}