{"title":"Effects of herbicide mixtures on the fertilizing capacity of bovine sperm","authors":"Diogo Ferreira Bicca , Rafaela Dalmolin Menezes , Laura Rohde Brondani , Monike Quirino , Larissa Thaísa Weide , Fábio Gallas Leivas , Daniela dos Santos Brum , Francielli Weber Santos Cibin","doi":"10.1016/j.reprotox.2025.109037","DOIUrl":"10.1016/j.reprotox.2025.109037","url":null,"abstract":"<div><div>Herbicides are the most commonly used pesticide type worldwide. In Brazil, glyphosate-, dichlorophenoxyacetic acid (2,4-D)-, and atrazine-based pesticide formulations are intensively applied to crops, and mixtures of these compounds occur frequently in the environment. Owing to their proximity to these areas and management practices, bovines are exposed to these pesticide mixtures, and their impact on their health is unknown. In this study, we evaluated the <em>in vitro</em> effects of herbicide mixtures on bovine sperm. Semen from four bulls was prepared as a pool and divided into groups: control, dimethyl sulfoxide (DMSO), glyphosate (Gly; 50 µg/mL), 2,4-D (0.11 µg/mL), atrazine (Atz; 0.0107 µg/mL), Gly + 2,4-D (GD), Gly + Atz (GA), Atz+ 2,4-D (AD) and Gly + 2,4-D + Atz (GDA). Sperm cells were evaluated after 3 h of incubation with the different treatments at 37℃. Results showed that the Gly, 2,4-D, and AD groups decreased progressive motility, mean path velocity, and beat cross frequency compared to the control group. Similarly, Gly and 2,4-D reduced curvilinear and straight-line velocities, and 2,4-D affected the amplitude of lateral head displacement. Although no differences in reactive species levels were detected, an overall reduction in antioxidant capacity was observed. Membrane integrity, acrosome damage, and mitochondrial membrane potential results did not differ significantly among the groups. However, the mixture diminished sperm fertilization capacity in groups GD, AD, and GDA, when compared to the control. No effects appeared in the DMSO group. Herbicides showed distinct impacts on bovine sperm, emphasizing the importance of evaluating pesticide mixtures thoroughly.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109037"},"PeriodicalIF":2.8,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144896738","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":"Eugenol mitigates glyphosate-induced testicular toxicity via modulation of oxidative stress, ER stress, RAGE/NLRP3 and PI3K/AKT signaling pathways in rats","authors":"Tuba Dogan , Ismail Bolat , Samet Tekin , Burak Cınar , Esra Aktas Senocak , Omercan Alat , Mesut Bünyami Halici","doi":"10.1016/j.reprotox.2025.109038","DOIUrl":"10.1016/j.reprotox.2025.109038","url":null,"abstract":"<div><div>Glyphosate (GLY), a widely used herbicide, has been implicated in male reproductive toxicity through mechanisms involving oxidative stress, apoptosis, and disrupted cellular signaling. This study evaluated the protective effects of eugenol (EU), a natural antioxidant, against GLY-induced testicular damage in rats. Thirty-five adult male rats were divided into five groups: Control, EU (100 mg/kg), GLY (150 mg/kg), GLY+EU (50 mg/kg), and GLY+EU (100 mg/kg). Treatments were administered orally for seven days. Testicular tissue was analyzed histologically (H&E staining), and PI3K/AKT signaling was assessed via immunohistochemistry and immunofluorescence. Oxidative stress markers (MDA, GSH, SOD, CAT, GPx) were measured biochemically. Gene expressions related to ER stress, RAGE, and NLRP3 were evaluated by qRT-PCR, while apoptotic (Bax, Bcl-2, Caspase-3), inflammatory (Beclin-1, NF-κB, TNF-α), and antioxidant (Keap1, Nrf2) protein levels were analyzed by western blotting. Co-treatment with EU, especially at 100 mg/kg, significantly ameliorated GLY-induced testicular toxicity by reducing oxidative and ER stress, inhibiting inflammation and apoptosis, and modulating the PI3K/AKT pathway. These findings highlight the potential of eugenol as a protective agent against GLY-induced reproductive toxicity through its regulatory effects on multiple molecular pathways.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109038"},"PeriodicalIF":2.8,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144889614","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}
Jinping Liu , Yi Cheng , Enfu Huang , Zhixiang Liu , Yun Zhou
{"title":"Estrogen receptor 1 (ESR1) promotes Di-butyl phthalate (DBP)-induced hypospadias by regulating mitophagy through PINK1-Parkin axis to inhibit ferroptosis","authors":"Jinping Liu , Yi Cheng , Enfu Huang , Zhixiang Liu , Yun Zhou","doi":"10.1016/j.reprotox.2025.109036","DOIUrl":"10.1016/j.reprotox.2025.109036","url":null,"abstract":"<div><div>This study reveals how Di-butyl phthalate (DBP), an estrogen-mimicking environmental pollutant, induces hypospadias by inhibiting ferroptosis through ESR1 activation and PINK1-Parkin-dependent mitophagy. Utilizing a prenatal DBP-exposed fetal rat hypospadias model, we observed significant downregulation of pro-ferroptotic ACSL4 and upregulation of anti-ferroptotic GPX4/SLC7A11 in urethral tissues, alongside elevated oxidative stress markers (MDA, Fe²⁺) and reduced glutathione (GSH). In vitro experiments using rat urethral plate fibroblasts (RUPFs) demonstrated that DBP enhanced ferroptosis resistance and promoted proliferation at concentrations below 200 μM. Mechanistically, DBP activated ESR1, which triggered mitophagy via the PINK1-Parkin pathway, reducing mitochondrial damage and reactive oxygen species (ROS) accumulation, thereby suppressing ferroptosis. Inhibition or silencing of ESR1 reversed these effects, restoring ferroptosis sensitivity and oxidative stress. These findings unveil a novel ESR1-mitophagy-ferroptosis regulatory axis, linking DBP exposure to hypospadias pathogenesis. The study not only elucidates a previously unrecognized molecular pathway underlying phthalate-induced congenital malformations but also identifies ESR1 and mitophagy as potential therapeutic targets. By integrating in vivo and in vitro approaches, this work advances the understanding of environmental endocrine disruptors’ role in developmental toxicity and provides actionable insights for mitigating their health impacts, aligning with current priorities in reproductive and environmental health research.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109036"},"PeriodicalIF":2.8,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908971","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}
Jingjing Yu , Wenjun Fu , Xinyi Wang , Xiang Zhang , Kun Xiong , Yuan Wang
{"title":"Study on the mechanism of different doses of lycium barbarum polysaccharides affecting sperm motility in Drosophila melanogaster","authors":"Jingjing Yu , Wenjun Fu , Xinyi Wang , Xiang Zhang , Kun Xiong , Yuan Wang","doi":"10.1016/j.reprotox.2025.109034","DOIUrl":"10.1016/j.reprotox.2025.109034","url":null,"abstract":"<div><div>Lycium barbarum, a Solanaceae plant, yields bioactive polysaccharides (LBP) in its dried mature fruits. LBP has demonstrated protective effects on the reproductive system. This study took <em>Drosophila melanogaster</em> as the experimental subject to investigate the dose-dependence of LBP on male reproductive capacity. The flies were orally administered LBP (0–2000 mg/L) by the CAFE method. Twenty-four hours later, sperm motility, ovulation rate and testicular gene expression were evaluated. Key results: LBP modulates sperm motility and female ovulation rate in a dose-dependent manner. The dose-response curves of <em>oamb, gish, zeste</em> and <em>cg9465</em> show an inverted U-shaped trend. LBP regulates spermatogenic genes through OAMB receptor. The PKA signal was positively correlated with histone methyltransferase (<em>zeste</em>), indicating that there are other regulatory pathways. Two-phase dose effects were observed: LBP enhanced motility at 0–150 mg/kg and 450–1000 mg/kg, while inhibited motility at 150–450 mg/kg and > 1000 mg/kg. In conclusion, the reproductive effects of LBP follow nonlinear dynamic laws. This complexity further highlights the necessity of conducting in-depth studies on each component of LBP in order to accurately assess its reproductive toxicity and optimize its therapeutic potential.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109034"},"PeriodicalIF":2.8,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144864238","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}
Yejin Kim , Yu-Jin Jo , Seung-Bin Yoon , Jeongwoo Kwon , Hyeong-Ju You , Changsic Youn , Young-Kug Choo , Ji-Su Kim
{"title":"Beauvericin disrupts G2/M transition and induces meiotic arrest during mouse oocyte maturation","authors":"Yejin Kim , Yu-Jin Jo , Seung-Bin Yoon , Jeongwoo Kwon , Hyeong-Ju You , Changsic Youn , Young-Kug Choo , Ji-Su Kim","doi":"10.1016/j.reprotox.2025.109032","DOIUrl":"10.1016/j.reprotox.2025.109032","url":null,"abstract":"<div><div>Beauvericin (BEA) is a mycotoxin produced by fungi of the genus <em>Fusarium</em> that causes adverse toxic effects in humans and livestock. Previous studies have demonstrated that BEA causes reproductive toxicity in pigs and juvenile sheep. However, the effects of BEA on meiotic resumption and the underlying mechanisms remain unclear. In this study, we investigated the molecular mechanisms underlying meiotic failure caused by the toxic effects of BEA on fully grown immature mouse oocytes. Exposure to BEA led to DNA damage, affected phosphatidylinositol 3-kinase/protein kinase B/phosphodiesterase 3 A (PI3K/AKT/PDE3A)-mediated cAMP signaling, and inhibited cyclin-dependent kinase (CDK) complex (MPF) activation by modulating CDK1 activity through altered expression of Wee1 and CDC25B. These disruptions ultimately led to germinal vesicle arrest during <em>in vitro</em> oocyte maturation. Our findings suggest that BEA treatment blocks germinal vesicle breakdown by affecting the PI3K/AKT/PDE3A-mediated cAMP-MPF pathway, resulting in the failure of meiotic progression and defects in the maturation of mammalian oocytes.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109032"},"PeriodicalIF":2.8,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966937","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}
Betul Yalcın , Tugce K. Kalkan , Zeynep B. Gonen , Eda Koseoglu , Gozde O. Onder , Nur S. Gokdemir , Munevver Baran , Arzu Yay
{"title":"Role of adipose-derived stem cell exosomes in paclitaxel-induced acute ovarian injury: An experimental approach","authors":"Betul Yalcın , Tugce K. Kalkan , Zeynep B. Gonen , Eda Koseoglu , Gozde O. Onder , Nur S. Gokdemir , Munevver Baran , Arzu Yay","doi":"10.1016/j.reprotox.2025.109033","DOIUrl":"10.1016/j.reprotox.2025.109033","url":null,"abstract":"<div><div>Paclitaxel (PTL) is commonly used in cancer therapy at varying doses and durations, often in combination with other chemotherapeutic agents. However, achieving therapeutic efficacy typically requires high doses, which are associated with considerable toxicity. Adipose-derived stem cells have shown therapeutic potential, particularly through the release of extracellular vesicles known as exosomes. This study investigated the potential protective effects of exosomes derived from adipose-derived mesenchymal stem cells (AMSC-Exos) in a rat model of PTL-induced acute ovarian injury. Twenty-eight rats were assigned to groups: control, PTL (7.5 mg/kg), AMSC-Exos (1 ×10<sup>6</sup> exosomes), and PTL+AMSC-Exos (7.5 mg/kg PTL + 1 × 10<sup>6</sup> exosomes). Three days after the administration, ovarian tissues were harvested for histological and biochemical analysis. Hematoxylin and eosin (H&E) and Masson's Trichrome (MT) staining revealed significant histopathological deterioration in the cortex and medulla of ovarian tissue in the PTL group compared to the PTL+AMSC-Exos group. Exosome treatment following PTL administration resulted in upregulation of VEGF and downregulation of HIF-1α, NF<sub>K</sub>B-p65, and IL-1β immunostaining intensities. Additionally, AMH immunostaining intensity was increased in primary, preantral, and secondary follicles. Levels of TNF-α, IL-1β, and IL-6 were significantly lower in the exosome treated group than in the PTL group, according to the results of the ELISA. These findings demonstrate that AMSC-Exos exhibited beneficial effects against PTL-induced acute ovarian damage by reducing histopathological alterations, inflammation, and HIF-1α expression, while enhancing VEGF expression and ovarian reserve. AMSC-Exos may represent a promising therapeutic approach for preventing chemotherapy-induced ovarian toxicity.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109033"},"PeriodicalIF":2.8,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144880143","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}
Yang Ma , Shiyi Huang , Yingshi Liang , Yuebin Zhu , Haofeng Huang , Bingna Zhang , Lungang Shi
{"title":"All-trans Retinoic Acid regulates cellular senescence of mouse embryonic palatal mesenchyme (MEPM) cells in developing cleft palates","authors":"Yang Ma , Shiyi Huang , Yingshi Liang , Yuebin Zhu , Haofeng Huang , Bingna Zhang , Lungang Shi","doi":"10.1016/j.reprotox.2025.109030","DOIUrl":"10.1016/j.reprotox.2025.109030","url":null,"abstract":"<div><h3>Background</h3><div>Non-syndromic cleft lip and palate is one of the most common congenital craniofacial malformations, however, its mechanism is not well understood. A number of relevant studies have confirmed that the cleft lip and palate is caused by the interaction of environmental and genetic factors. Retinoic acid is one of the metabolites of vitamin A and is involved in various physiological functions in the body, which is essential for the regulation of cell growth and differentiation and the maintenance of normal human development. However, excessive intake of All-trans Retinoic Acid (atRA) is one of the etiological factors contributing to the development of cleft palate. Cell senescence is a hot topic and a new direction in recent years, which is related to the occurrence of various tumors and diseases. From the perspective of cellular senescence, this study aimed to verify the mechanism of action of atRA-induced cleft palate in model of mouse embryonic palatal mesenchyme (MEPM) cells. This study aims to verify whether the pathogenesis of the atRA-induced cleft palate occurs because the cellular senescence of MEPM cells via 53/p21 signaling pathway.</div></div><div><h3>Methods</h3><div>The palate tissues of atRA-induced cleft palate were obtained for section staining and western blotting test. MEPM cells were obtained from palate tissues and cultured in vitro, and then MEPM cells in vitro were treated with atRA. To verify that the atRA could affect the cell proliferative ability and cellular senescence of MEPM cells through the p53/p21 pathway, which resulted in the failure of palatal fusion in embryonic mice, leading to cleft palate. The senescence-associated β-Galactosidase staining, CCK-8 activity assay, cell cycle analysis and western blotting test were used.</div></div><div><h3>Results</h3><div>In atRA-induced cleft palate group, tissue sections of the palate showed that there was no change in TUNEL apoptosis fluorescence staining. However, there was increased cellular senescence in MEPM cells treated with atRA as characterized by enhancing senescence-associated β-galactosidase (SA-β-Gal) activity, reducing cell proliferation, inducing MEPM cells cell cycle arrest at G1 phase and increasing expression of the senescence markers p53 and p21. p53/p21 signaling pathway was up-regulated, which could induce the cells to undergo senescence, resulting in a decrease of cell proliferative ability.</div></div><div><h3>Conclusions</h3><div>Our experimental results have shown that atRA could increase cell senescence through the p53/p21 signaling pathway in MEPM cells and diminish cell activity and proliferation ability, inducing the occurrence of cellular senescence and resulting in cleft palate in the embryonic mouse. From the viewpoint of cellular senescence, this study is intended to expand the mechanism of action of atRA-induced cleft palate as well as to provide new ideas for the study of the etiology of cleft palate.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109030"},"PeriodicalIF":2.8,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859564","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}
Charles S. da Costa , Vinícius Bermond Marques , Jandinay Mageski , Paulo Caleb J.L. Santos , Rodrigo Alves Faria , Isabela V. Sarmento , Poliana Borges de Oliveira , Maira Krause , Maria Tereza W. D Carneiro , Leonardo dos Santos , Jones B. Graceli
{"title":"Chronic iron overload disrupts the reproductive tract and leads to infertility: From a clinical case report to the experimental study of reproduction in female mice","authors":"Charles S. da Costa , Vinícius Bermond Marques , Jandinay Mageski , Paulo Caleb J.L. Santos , Rodrigo Alves Faria , Isabela V. Sarmento , Poliana Borges de Oliveira , Maira Krause , Maria Tereza W. D Carneiro , Leonardo dos Santos , Jones B. Graceli","doi":"10.1016/j.reprotox.2025.109031","DOIUrl":"10.1016/j.reprotox.2025.109031","url":null,"abstract":"<div><div>Iron overload is associated with reproductive abnormalities. For example, a case study showed that despite the iron status normalization following phlebotomies and chelation therapy, a woman with juvenile hemochromatosis (JH) continued to exhibit persistent atrophic ovaries, accompanied by prolonged amenorrhea by clinical evaluations. However, the iron overload consequences in the female hypothalamic-pituitary-gonadal (HPG) axis are incompletely understood. Based on the case-report follow-up of a woman diagnosed with JH, this study elucidated the effects of chronic iron overload on the female mouse model, with a special focus on iron-induced consequences in the HPG axis. Female mice were injected with iron (10 mg/mouse/day) five times per week for four weeks, and iron deposits and the reproductive tissues morphology, hormone levels, reactive oxygen species (ROS), and fertility were assessed. Iron-overloaded mice had increased iron levels in serum, hypothalamus, pituitary, ovary, and uterus. Iron-overloaded mice displayed irregular estrous cycles, abnormal folliculogenesis and estrogen levels, reduced corpora lutea and increased atretic follicle numbers. Furthermore, iron overload induced uterine atrophy, along with uterine and ovarian fibrosis. Further iron-overloaded mice increased ROS in the pituitary, ovary and uterus. Positive correlations were found between serum iron levels and ovarian atretic follicles and collagen deposition, and between uterine iron levels and uterine ROS and collagen deposition. In the fertility evaluation, no pups or litters were observed over 90 days in the iron-overloaded mice, suggesting that iron overload causes infertility. Collectively, these findings indicate that chronic iron overload leads to HPG axis abnormalities due to iron accumulation and ROS generation.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109031"},"PeriodicalIF":2.8,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144842119","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}
Bárbara Campos Jorge , Julia Polotto da Silva , Sara Tawany Caetano dos Santos , Fernando Barbosa , Valéria Cristina Sandrim , Arielle Cristina Arena
{"title":"Potential role of endocrine-disrupting chemicals in preeclampsia: A hypothesis based on integration of epidemiological and experimental evidence","authors":"Bárbara Campos Jorge , Julia Polotto da Silva , Sara Tawany Caetano dos Santos , Fernando Barbosa , Valéria Cristina Sandrim , Arielle Cristina Arena","doi":"10.1016/j.reprotox.2025.109029","DOIUrl":"10.1016/j.reprotox.2025.109029","url":null,"abstract":"<div><div>Preeclampsia (PE) is a complex hypertensive disorder and a leading cause of maternal and perinatal morbidity worldwide. Emerging evidence suggests that exposure to endocrine-disrupting chemicals (EDCs) may contribute to the etiology of PE, yet this association remains underexplored. This review aimed to investigate epidemiological and experimental studies assessing the potential link between EDC exposure and PE development. A literature search was conducted across PubMed, ScienceDirect, and Google Scholar for original articles published in the last ten years. Forty studies were selected, including epidemiological cohorts, <em>in vivo</em>, and <em>in vitro</em> models, focusing on the association between EDCs and PE or related biomarkers. Epidemiological findings were heterogeneous: while large cohorts often showed no association, several case-control studies linked specific EDCs, such as bisphenol A, phthalates, cadmium, and PFOS, to increased PE risk and elevated blood pressure. Experimental evidence revealed that EDCs impair key placental processes, including decidualization, angiogenesis, and trophoblast invasion. These disruptions were often accompanied by oxidative stress, hormonal imbalances, and endothelial dysfunction, central features in PE pathogenesis. In vivo models also replicated PE-like syndrome after EDC exposure. Although current epidemiological evidence remains inconsistent, mechanistic studies strongly support the biological plausibility of EDC involvement in PE. This review highlights that the contribution of EDCs to PE may be underestimated and calls for multidisciplinary research to clarify exposure thresholds, vulnerable windows, and population-specific susceptibilities.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109029"},"PeriodicalIF":2.8,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144817444","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}
Jintao Yuan , Xinrui Li , Songci Yan , Chengyu Luo , Sijia Xian , Yuanyuan Li , Jiang Wu
{"title":"Microcystin-LR disrupts ovarian granulosa cell glycolysis via GSK3β-Mediated HK2 mitochondrial dissociation: Evidence from integrated In Vivo and In Vitro models","authors":"Jintao Yuan , Xinrui Li , Songci Yan , Chengyu Luo , Sijia Xian , Yuanyuan Li , Jiang Wu","doi":"10.1016/j.reprotox.2025.109028","DOIUrl":"10.1016/j.reprotox.2025.109028","url":null,"abstract":"<div><div>Reproductive disorders, a significant global health challenge, impact roughly 10 % of couples of reproductive ages. Notably, among these couples, 60–70 % of reproductive disorders are associated with women. Current evidence highlights that glycolysis plays an essential role in female reproductive function and is critical to follicle development and maturation. Microcystins (MCs), monocyclic heptapeptide toxins produced by freshwater cyanobacteria, include various isomers. Among them, microcystin-leucine-arginine (MC-LR) is the most prevalent and toxic form and is commonly found in water and food sources. However, the precise effects of MC-LR on glycolysis and its underlying mechanisms remain poorly understood. Therefore, this study aims to explore whether MC-LR induces reproductive defects in female mammals by disrupting glycolysis in human ovarian granulosa cells and mouse ovarian tissue, and to clarify its underlying mechanism.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109028"},"PeriodicalIF":2.8,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822452","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}