Reproductive toxicology最新文献

{"title":"Phthalate monoesters affect membrane fluidity and cell-cell contacts in endometrial stromal adherent cell lines and spheroids","authors":"Darja Lavogina ,&nbsp;Keiu Kask ,&nbsp;Sergei Kopanchuk ,&nbsp;Nadja Visser ,&nbsp;Mary Laws ,&nbsp;Jodi A. Flaws ,&nbsp;Theodora Kunovac Kallak ,&nbsp;Matts Olovsson ,&nbsp;Pauliina Damdimopoulou ,&nbsp;Andres Salumets","doi":"10.1016/j.reprotox.2024.108733","DOIUrl":"10.1016/j.reprotox.2024.108733","url":null,"abstract":"<div><div>Phthalate monoesters have been identified as endocrine disruptors in a variety of models, yet understanding of their exact mechanisms of action and molecular targets in cells remains incomplete. Here, we set to determine whether epidemiologically relevant mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) can affect biological processes by altering cell plasma membrane fluidity or formation of cell-cell contacts. As a model system, we chose endometrial stromal cell lines, one of which was previously used in a transcriptomic study with MEHHP or MEHHP-containing mixtures. A short-term exposure (1 h) of membrane preparations to endocrine disruptors was sufficient to induce changes in membrane fluidity/rigidity, whereas different mixtures showed different effects at various depths of the bilayer. A longer exposure (96 h) affected the ability of cells to form spheroids and highlighted issues with membrane integrity in loosely assembled spheroids. Finally, in spheroids assembled from T-HESC cells, MEHHP interfered with the formation of cell-cell contacts as indicated by the immunostaining of <em>zonula occludens</em> 1 protein. Overall, this study emphasized the need to consider plasma membrane, membrane-bound organelles, and secretory vesicles as possible biological targets of endocrine disruptors and offered an explanation for a multitude of endocrine disruptor roles documented earlier.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"130 ","pages":"Article 108733"},"PeriodicalIF":3.3,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142433217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the hypothetical links between environmental pollutants, diet, and the gut-testis axis: The potential role of microbes in male reproductive health","authors":"Itishree Dubey ,&nbsp;Nandheeswari K ,&nbsp;Vigneshwaran G ,&nbsp;Gourav Rohilla ,&nbsp;Lalruatmawii ,&nbsp;Pratik Naxine ,&nbsp;Jayapradha P ,&nbsp;Mahesh Rachamalla ,&nbsp;Sapana Kushwaha","doi":"10.1016/j.reprotox.2024.108732","DOIUrl":"10.1016/j.reprotox.2024.108732","url":null,"abstract":"<div><div>The gut system, commonly referred to as one of the principal organs of the human \"superorganism,\" is a home to trillions of bacteria and serves an essential physiological function in male reproductive failures or infertility. The interaction of the endocrine-immune system and the microbiome facilitates reproduction as a multi-network system. Some recent studies that link gut microbiota to male infertility are questionable. Is the gut-testis axis (GTA) real, and does it affect male infertility? As a result, this review emphasizes the interconnected links between gut health and male reproductive function <em>via</em> changes in gut microbiota. However, a variety of harmful (endocrine disruptors, heavy metals, pollutants, and antibiotics) and favorable (a healthy diet, supplements, and phytoconstituents) elements promote microbiota by causing dysbiosis and symbiosis, respectively, which eventually modify the activities of male reproductive organs and their hormones. The findings of preclinical and clinical studies on the direct and indirect effects of microbiota changes on testicular functions have revealed a viable strategy for exploring the GTA-axis. Although the GTA axis is poorly understood, it may have potential ties to reproductive issues that can be used for therapeutic purposes in the future.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"130 ","pages":"Article 108732"},"PeriodicalIF":3.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142433218","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":"Trifluoperazine effect on human sperm: The accumulation of reactive oxygen species and the decrease in the mitochondrial membrane potential","authors":"Houpeng Wang ,&nbsp;Cheng Cheng ,&nbsp;Jing Ding ,&nbsp;Ruirui Qian ,&nbsp;Tao Luo ,&nbsp;Liping Zheng ,&nbsp;Ying Chen","doi":"10.1016/j.reprotox.2024.108730","DOIUrl":"10.1016/j.reprotox.2024.108730","url":null,"abstract":"<div><div>A strong link between antipsychotic drug use and reduced human sperm quality has been reported. Trifluoperazine (TFP), a commonly used antipsychotic, is now being explored for anticancer applications. Although there are hints that TFP might affect the male reproductive system, its impact on human sperm quality remains uncertain. Using a human sperm and TFP in vitro coculture system, we examined the effect of TFP (12.5, 25, 50 and 100 μM) on human sperm function and physiological parameters. The results showed that 50 μM and 100 μM TFP induced the accumulation of reactive oxygen species (ROS) and a decrease in the mitochondrial membrane potential (MMP) of human sperm, leading to decreased sperm viability, while 25 μM TFP inhibited only the penetration ability, total sperm motility, and progressive motility. Although 12.5 μM and 25 μM TFP increased [Ca²⁺]_i in human sperm, they did not affect capacitation or the acrosome reaction. These results may be explained by the observation that 12.5 μM and 25 μM TFP did not increase tyrosine phosphorylation in human sperm, although TFP increased [Ca²⁺]_i in a time-course traces similar to that of progesterone. Our results indicated that TFP could cause male reproductive toxicity by inducing the accumulation of ROS and a decrease in the MMP in human sperm.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"130 ","pages":"Article 108730"},"PeriodicalIF":3.3,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381582","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":"Efcab7 deletion sensitizes mice to the teratogenic effects of gastrulation-stage alcohol exposure","authors":"Eric W. Fish ,&nbsp;Karen E. Boschen ,&nbsp;Scott E. Parnell","doi":"10.1016/j.reprotox.2024.108729","DOIUrl":"10.1016/j.reprotox.2024.108729","url":null,"abstract":"<div><div>Alcohol exposure during the gastrulation stage of development can disrupt Sonic hedgehog (Shh) signaling and cause eye, craniofacial, and brain defects. One of the genes that regulates Shh signaling is <em>Efcab7,</em> which encodes a protein that facilitates the actions of Smoothened (Smo), a critical component of the Shh pathway. Previous work from our lab has demonstrated that <em>Efcab7</em> is differentially expressed between two sub-strains of C57BL/6 mice that differ in their sensitivity to gastrulation-stage alcohol exposure. The more alcohol-sensitive C57BL/6 J mice express lower levels of <em>Efcab7</em> during gastrulation than do the less alcohol-sensitive C57BL/6NHsd mice. The current study examined whether partial or full <em>Efcab7</em> deletions render mice more sensitive to gastrulation-stage alcohol exposure and affect the sensitivity to other modulators of Shh signaling that cause craniofacial malformations. <em>Efcab7</em>^<em>+/-</em> dams were mated with <em>Efcab7</em>^<em>+/-</em> sires to produce <em>Efcab7</em>^<em>+/+</em>, <em>Efcab7</em>^<em>+/-</em>, and <em>Efcab7</em>^<em>-/-</em> fetuses. On gestational day 7 (GD 7), they received either alcohol (two doses of 2.9 g/kg, i.p., given 4 hours apart), the Smo antagonist vismodegib (40 mg/kg, or vehicle, p.o.), the Smo agonist SAG (20 mg/kg) or the appropriate vehicles. GD 17 fetuses were collected and examined for ocular and craniofacial dysmorphology. As compared to <em>Efcab7</em>^<em>+/+</em> fetuses, <em>Efcab7</em>^<em>-/-</em> fetuses exposed to alcohol or vismodegib treatment had more severe ocular and craniofacial malformations. In contrast, <em>Efcab7</em>^<em>-/-</em> fetuses had less severe malformations induced by SAG. These results confirm that <em>Efcab7</em> can modify responses to Shh agonists and antagonists and further identify <em>Efcab7</em> as a gene important for the sensitivity to gastrulation-stage alcohol exposure.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"130 ","pages":"Article 108729"},"PeriodicalIF":3.3,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375891","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":"Vulnerable periods for the mouse mammary gland: Comparison of the effects of ethinyl estradiol exposures during two early stages of development","authors":"Zachary W. Clark ,&nbsp;Joshua P. Mogus ,&nbsp;Jenna Marando,&nbsp;Reed S. Effenson,&nbsp;Laura N. Vandenberg","doi":"10.1016/j.reprotox.2024.108722","DOIUrl":"10.1016/j.reprotox.2024.108722","url":null,"abstract":"<div><div>The mammary gland is responsive to endogenous hormones and environmental chemicals that are estrogen receptor (ER) agonists. The mouse mammary gland offers the opportunity to dissect the most sensitive windows of exposure. 17α-ethinyl estradiol (EE2) is a pharmaceutical ER agonist that often serves as a positive control for estrogen-active chemicals. Here, adult female mice were exposed to EE2 starting either at pregnancy day 7, or on lactational day 1, and exposures continued until the litters were weaned. The pups were therefore exposed during gestation + the juvenile period, or during the juvenile period alone. The morphology of the mammary gland was evaluated in both male and female offspring at two life stages: weaning (postnatal day [PND]21) and at puberty (PND32). Other hormone-sensitive outcomes evaluated included body weight, anogenital index, frequency of open vagina, and weight of the uterus. We found age- and sex-dependent effects of EE2 on these estrogen-responsive endpoints including the morphology of the mammary gland. Importantly, EE2 altered mammary gland morphology even when exposures were limited to the juvenile period. However, the number of endpoints that were affected in animals from the EE2-Juvenile-Only period were fewer, and typically of a lower magnitude, compared to those observed in the EE2-Gest-Juvenile group. Understanding the effects of environmental estrogen exposures during the juvenile period is critical because humans are exposed to estrogenic pollutants throughout life, including in early childhood.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"130 ","pages":"Article 108722"},"PeriodicalIF":3.3,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352917","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":"Review of embryo-fetal developmental toxicity studies performed for pharmaceuticals approved by FDA in 2022 and 2023","authors":"Paul Barrow","doi":"10.1016/j.reprotox.2024.108727","DOIUrl":"10.1016/j.reprotox.2024.108727","url":null,"abstract":"<div><div>92 novel drugs were approved by the FDA in 2022–2023. 48 of these approvals were for orphan indications. Embryofetal development (EFD) studies were conducted for 79 % of approvals. Rats and rabbits were the most common species used (77 % and 62 % of studies, respectively). For the testing of biopharmaceuticals, rodents were more often used (43 % of EFD studies) than non-human primates (29 %) and rabbits (29 %). Most (75 %) biopharmaceuticals intended to treat cancer were approved without EFD studies. Amongst the 41 drugs for which both rat and rabbit EFD studies were performed, the rabbit appeared more sensitive to both maternal toxicity and developmental toxicity (61 % and 63 % of drugs, respectively). Most drugs (76 %) showed more than a 2-fold difference in the LOAEL for developmental toxicity between the rat and rabbit. EFD studies were not required for drugs with a mode of action known to pose a clear hazard for pregnancy and further EFD studies were generally not performed when clinically relevant developmental effects had already been observed in one species or in a preliminary EFD study. Many drug labels showed minor deviations from the PLLR rule: the metric used to calculate exposure margins and the presence or absence of maternal toxicity were not always specified. These omissions, however, are of little significance for the prescriber. The five reviews in this series now show compiled information on EFD studies for all small molecule pharmaceuticals approved since 2014 and for all therapeutic monoclonal antibodies approved to date.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"130 ","pages":"Article 108727"},"PeriodicalIF":3.3,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352916","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 mediating role of abnormal ZEB1 methylation in the association between nickel exposure and non-syndromic orofacial cleft","authors":"Yongyan Chen ,&nbsp;Yaquan Pan ,&nbsp;Lijun Liu,&nbsp;Yingnan Guo,&nbsp;Lei Jin,&nbsp;Aiguo Ren,&nbsp;Linlin Wang","doi":"10.1016/j.reprotox.2024.108728","DOIUrl":"10.1016/j.reprotox.2024.108728","url":null,"abstract":"<div><div>Our previous study found a positive relationship between fetal nickel exposure and the risk of OFCs. The teratogenic mechanism of nickel is not clear. In this study, we aim to examine the mediating effect of DNA methylation on the association of nickel(Ni) exposure with NSOFC in fetuses. 10 cases and 10 controls was used for screening target gene by Illumina Infinium Methylation EPIC(850k) BeadChip. 36 cases and 78 controls was conducted to determine DNA methylation level of selected gene in umbilical cord blood by Mass spectrometry assay. Mediation analysis was used to evaluate the potential mediating effect of selected gene methylation on the relation between concentrations of Ni and the risk for NSOFC. In the discovery stage, ZEB1 gene was identified to be hypermethylated in both nickel exposure and NSOFC group for validation. In the verification stage, the overall average methylation level of ZEB1 was significant higher in NSOFC cases(median = 8.70, interquartile range(IQR): 5.75–11.53) as compared to controls (median = 5.35, IQR: 4.30–7.78). The risk for NSOFC was increased by 1.43-fold with hypermethylation of ZEB1. Significant correlation was observed between concentrations of Ni in umbilical cord and methylation level of ZEB1. The hypermethylation of ZEB1 had a mediating effect by 20.47 % of total effect of Ni on NSOFC risk. Hypermethylation of ZEB1 is associated with the risk for NSOFC and may partially explain the association between Ni exposure and NSOFC risk. Our findings provide new insights into the epigenetic mechanisms underlying NSOFC and suggesting potential targets for future therapeutic interventions.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"130 ","pages":"Article 108728"},"PeriodicalIF":3.3,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142322804","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":"Minor changes to circulating steroid hormones in female rats after perinatal exposure to diethylstilbestrol or ketoconazole","authors":"Paraskevi Vazakidou ,&nbsp;Nora Bouftas ,&nbsp;Manuel Heinzelmann ,&nbsp;Hanna K.L. Johansson ,&nbsp;Terje Svingen ,&nbsp;Pim E.G. Leonards ,&nbsp;Majorie B.M. van Duursen","doi":"10.1016/j.reprotox.2024.108726","DOIUrl":"10.1016/j.reprotox.2024.108726","url":null,"abstract":"<div><div>Current chemical test strategies lack sensitive markers for detecting female reproductive toxicity caused by endocrine disrupting chemicals (EDCs). In search of a potentially sensitive readout, the steroidogenic disrupting effects of the well-known EDCs ketoconazole (KTZ) and diethylstilbestrol (DES) were investigated in vitro and on circulating steroid hormones in perinatally exposed female Sprague-Dawley rats. Twenty-one steroid hormones were analysed using LC-MS/MS in plasma from female rat offspring at postnatal day (PD) 6, 14, 22, 42 and 90. Most circulating steroid hormone levels increased with age except for estrone (E1), estradiol (E2) and backdoor pathway androsterone (ANDROST), which decreased after PD 22. Perinatal exposure to DES did not affect circulating steroid hormone levels at any dose or age compared to controls. KTZ exposure resulted in dose-dependent increase of corticosterone (CORTICO) at PD 6 and PD 14, with statistical significance only at PD 14. In the in vitro gold standard H295R steroidogenesis assay, twenty-one steroid hormones were measured instead of only T and E2. DES had subtle effects on steroidogenesis, whereas KTZ decreased most steroid hormones, but increased CORTICO, progesterone (P4), estriol (E3) initially (around 0.1–1 µM) before decreasing. Our data suggests that circulating steroidomic profiling may not be a sensitive readout for EDC-induced female reproductive toxicity. Further studies are needed to associate H295R assay steroidomic profiles with in vivo profiles, especially in target tissues such as adrenals or gonads. Expanding the H295R steroidogenic assay to include a comprehensive steroidomic profile may enhance its regulatory applicability.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"130 ","pages":"Article 108726"},"PeriodicalIF":3.3,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352915","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 systematic review of bleomycin-induced gonadotoxicity: Mechanistic implications for male reproductive health and fertility","authors":"Ana Lobo de Almeida ,&nbsp;Ana Fortuna ,&nbsp;Mário Sousa ,&nbsp;Rosália Sá","doi":"10.1016/j.reprotox.2024.108721","DOIUrl":"10.1016/j.reprotox.2024.108721","url":null,"abstract":"<div><div>Long-term cancer treatment complications in men include testicular dysfunction and infertility. Although various chemotherapies have been studied, there is limited evidence on their effects, especially for bleomycin. Despite its known lung toxicity, bleomycin’s impact on male reproductive health is not well-researched. This systematic review aimed to evaluate bleomycin’s effects on testicular function and fertility. A search of PubMed and Web of Science identified seven relevant animal studies on bleomycin's gonadotoxicity. The research, limited to animal models, shows that bleomycin significantly disrupts male reproductive health, including DNA damage in sperm, analogous to its effects on cancer cells, and notable histopathological changes in rodent testes. It reduces sperm quality and testosterone levels, correlating with Leydig cell degeneration and inflammatory responses, which further aligns with the drug’s known capacity to induce lung inflammation. Due to the inherent limitations in extrapolating results from rodents to humans, further research, particularly in humans, is needed to confirm these findings, assess hormonal impacts, temporal patterns of effects (whether transient or permanent), and their impacts implications for offspring, as well explore potential mitigation strategies. These findings are a first step in raising awareness among clinicians about bleomycin's fertility risks and developing strategies for fertility preservation.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"130 ","pages":"Article 108721"},"PeriodicalIF":3.3,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bisphenol A-induced oxidative stress increases the production of ovarian cancer stem cells in mice","authors":"Sumit Rajaura ,&nbsp;Nitin Bhardwaj ,&nbsp;Ashutosh Singh ,&nbsp;Ram Babu ,&nbsp;Neelujain Gupta ,&nbsp;Mohammad Z. Ahmed","doi":"10.1016/j.reprotox.2024.108724","DOIUrl":"10.1016/j.reprotox.2024.108724","url":null,"abstract":"<div><div>Bisphenol A (BPA) belongs to the endocrine disruptor chemicals (EDCs) causing various reproductive disorders in females. We analysed the toxic effects of BPA in the uterus and ovaries. The BPA was administered orally with the repeated low dose (LD, 1 mg/kg) and high dose (HD, 5 mg/kg) of body weight on alternate days for 4 months via oral gavage to Swiss mice. BPA administration decreases body weight, ovarian weight and size at LD, but increases ovarian weight and size at HD. The uterus weight, length, and diameter were increased in both the treated groups. The histopathological data show decreased ovarian follicle size, epithelial hyperplasia, and lymphocytic infiltration in the ovary. The BPA-treated uterus shows increased vascularization, atrophied endometrium and myometrium, and endometrial hyperplasia (EH) with aberrant glandular growth. The cancer stem cells (CSCs) in the ovaries were identified based on staining with anti-mouse CD44 and anti-mouse CD133 antibodies and analysed by flow cytometry. Three different populations of ovarian CSCs: CD44⁺CD133^-, CD44⁺CD133⁺, and CD44−CD133+, can be recognised based on the intensity of these receptors. CD44⁺CD133^- and CD44⁺CD133⁺ cell percentages were increased in BPA-treated groups. CD44⁻CD133⁺ were increased in LD but decreased in HD. The BPA administration also induces ROS production, which decreases the expression of antioxidant genes Superoxide dismutase 1 (SOD1), Superoxide dismutase 2 (SOD2), Catalase (CAT), Glutathione peroxidase 1 (GPX1), and Forkhead box O3 (FOXO3) in ovarian cells. In conclusion, BPA exposure induced an inflammatory response, increased CSC proportions, induced ROS, and decreased antioxidant responses in the ovaries.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"130 ","pages":"Article 108724"},"PeriodicalIF":3.3,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142322803","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}