Chuting Wang , Long Zhang , Daidi Gui , Wenjing Zou , Menglei Zhu , Yu Liu , Lei Hua , Changlian Li , Rui Ding
{"title":"Effect of 1-nitropyrene exposure on the biological behavior of trophoblast cells","authors":"Chuting Wang , Long Zhang , Daidi Gui , Wenjing Zou , Menglei Zhu , Yu Liu , Lei Hua , Changlian Li , Rui Ding","doi":"10.1016/j.reprotox.2025.108865","DOIUrl":"10.1016/j.reprotox.2025.108865","url":null,"abstract":"<div><div>1-nitropyrene (1-NP) is a toxic component of PM<sub>2.5</sub> that adversely affects human health, especially pregnant women; however, the mechanisms are still unclear. This study aims to explore the mechanisms by which 1-NP influences trophoblast cell behaviors. HTR8/Svneo cells were treated by different concentrations of 1-NP (0, 5, 10, 20 μM) to assess clonogenic, invasive, and migratory abilities. Western blot analysis was used to assess the expression of EMT and Wnt/β-catenin pathway proteins. 1-NP significantly inhibited HTR8/Svneo cell clonogenic ability, especially at 10 μM and 20 μM (<em>P</em> < 0.01). Invasiveness decreased by 68.44 % at 5 μM (<em>P</em> < 0.05), and migration was significantly inhibited at 10 μM and 20 μM (<em>P</em> < 0.05). Western blot revealed increased E-cadherin and decreased Vimentin (<em>P</em> < 0.01), elevated β-catenin (<em>P</em> < 0.05), and reduced APC (<em>P</em> < 0.01). In summary, 1-NP impacts trophoblast cell clonogenicity, invasion, and migration by modulating EMT and Wnt/β-catenin pathways, providing novel insights into its biological effects on trophoblast cells.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"133 ","pages":"Article 108865"},"PeriodicalIF":3.3,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534070","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}
Carla Giovana Basso , Bruno Alves Rocha , Ivana Rippel Hauer , Jonas Carneiro Cruz , Francisco Furtado Filho , Fernando Barbosa Jr , Anderson Joel Martino-Andrade
{"title":"Associations between urinary and follicular fluid concentrations of phthalate metabolites and reproductive outcomes in Brazilian women undergoing fertility treatment","authors":"Carla Giovana Basso , Bruno Alves Rocha , Ivana Rippel Hauer , Jonas Carneiro Cruz , Francisco Furtado Filho , Fernando Barbosa Jr , Anderson Joel Martino-Andrade","doi":"10.1016/j.reprotox.2025.108868","DOIUrl":"10.1016/j.reprotox.2025.108868","url":null,"abstract":"<div><div>Existing literature indicates that phthalates can be toxic to the ovaries, negatively affecting female reproduction and potentially influencing outcomes in assisted reproductive technology (ART). However, data on associations between urinary and/or follicular fluid phthalate concentrations and ART outcomes in South American women are scarce. Therefore, in this prospective study, we recruited 93 women (n = 119 cycles) undergoing ART at a fertility clinic in Brazil. They provided urine and follicular fluid (FF) samples, from which we measured the concentrations of the 15 phthalate metabolites more frequently found in Brazilian populations. We documented both laboratorial and clinical outcomes, estimating associations using negative binomial regression. Our findings revealed that specific oocyte and embryo development parameters were associated with urinary concentrations of phthalate metabolite. Particularly, number of follicles, maturation, as well as blastulation were negatively associated with Mono-benzyl phthalate (MBzP). Similarly, urinary mono-ethyl phthalate (MEP) was associated with lower rates of maturation, good quality and blastulation. However, some parameters positively associated with mono-(carboxyisooctyl) phthalate (MCiOP), including maturation, good quality, and blastulation. We also observed certain associations between embryo development and FF concentrations of phthalate metabolite, although the magnitude and direction of these associations differed among various metabolites. Overall, our results suggest that urinary and FF concentrations of phthalate metabolite may be linked to altered outcomes in ART cycles. However, further studies are needed to clarify the extent of this impact. Our results support previous literature and is the first to evaluate urinary and FF phthalate metabolites concentrations in South American women undergoing infertility treatment.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"133 ","pages":"Article 108868"},"PeriodicalIF":3.3,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537414","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}
Daniele Marcoccia , Marta Mollari , Flavia Silvia Galli , Camilla Cuva , Valentina Tassinari , Alberto Mantovani
{"title":"Prostate as a target of endocrine disrupting chemicals: Relevance, pathways, assays","authors":"Daniele Marcoccia , Marta Mollari , Flavia Silvia Galli , Camilla Cuva , Valentina Tassinari , Alberto Mantovani","doi":"10.1016/j.reprotox.2025.108867","DOIUrl":"10.1016/j.reprotox.2025.108867","url":null,"abstract":"<div><div>Prostate, the main accessory gland of the male reproductive system, is a critical but yet overlooked target for Endocrine Disruptors (EDs), affecting the male reproductive system. Prostate is essential for male fertility; indeed, the prostatic fluid is the main component of seminal fluid, which is essential for the activation and capacitation of sperm cells. Furthermore, the prostate is tightly regulated by androgen signaling and is an important site for endocrine-related tumorigenesis. The following systematic review assesses and discusses the available literature evidence regarding the use of the androgen-dependent human prostate cell line LNCaP, in which up- or down-regulation of androgen signaling is assessed by measuring a clinically relevant marker, the Prostate-Specific Antigen (PSA). The data set is still limited: 30 articles, mainly dealing on natural substances and plant extracts, met the eligibility criteria. However, the results support the potential of the PSA assay testing on LNCaP cells in evaluating endocrine-related effects on prostate function as well as to identifying substances that may affect androgen-regulated pathways. Overall, the findings encourage further investigations with a broader range of substances with different modes of action.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"133 ","pages":"Article 108867"},"PeriodicalIF":3.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143529675","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}
Sami Teeny , Zachery R. Jarrell , Nickilou Y. Krigbaum , Piera M. Cirillo , Young-Mi Go , Barbara A. Cohn , Dean P. Jones
{"title":"Environmental basis for early onset breast cancer","authors":"Sami Teeny , Zachery R. Jarrell , Nickilou Y. Krigbaum , Piera M. Cirillo , Young-Mi Go , Barbara A. Cohn , Dean P. Jones","doi":"10.1016/j.reprotox.2025.108866","DOIUrl":"10.1016/j.reprotox.2025.108866","url":null,"abstract":"<div><div>Pregnancy provokes a heightened amino acid requirement, especially in the third trimester. Alterations to late pregnancy amino acid metabolism have been associated with environmental breast carcinogen exposures, including DDT and PFAS. This project examined whether maternal serum amino acids in late pregnancy are associated with subsequent breast cancer risk. Archival third-trimester serum samples from 172 women who were later diagnosed with breast cancer were compared to samples from 351 women without known breast cancer. A prospective metabolome-wide association study (MWAS) for breast cancer cases showed that associated amino acid pathways included lysine, arginine, proline, aspartate, asparagine, alanine, tyrosine, tryptophan, histidine and branched-chain amino acids. Lower mean concentrations of individual amino acids, including histidine, threonine, lysine, and proline, were associated with an increased risk of breast cancer, and network analyses showed that these amino acids were negatively associated with protective breast cancer risk factors. Prospective MWAS for breast cancer cases diagnosed within 15 years of sample collection showed pathway associations for tryptophan, histidine, lysine methionine, and cysteine metabolism. Nutrient stresses caused by low amino acid levels impair immunosurveillance and activate oncogenic mechanisms of cell survival, thereby providing mechanisms by which environmental exposures in late pregnancy can contribute to breast cancer risk.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"133 ","pages":"Article 108866"},"PeriodicalIF":3.3,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524295","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}
Dan Chen, Zhi-xuan Xing, Sheng-peng Li, Tao Lu, Jia-xin Wang, Ya-xian Wu, Qing-feng Pang
{"title":"Preconception maternal hyperoxia exposure causes cardiac insufficiency through induction of mitochondrial toxicity in mice offspring","authors":"Dan Chen, Zhi-xuan Xing, Sheng-peng Li, Tao Lu, Jia-xin Wang, Ya-xian Wu, Qing-feng Pang","doi":"10.1016/j.reprotox.2025.108864","DOIUrl":"10.1016/j.reprotox.2025.108864","url":null,"abstract":"<div><div>Although essential, excessive oxygen is toxic. The adverse effects of maternal hyperoxygenation have recently garnered attention. However, the potential toxicity of maternal hyperoxia exposure before pregnancy and its effects on offspring development remain unclear. This study aims to investigate the cardiac developmental toxicity of maternal pre-pregnancy hyperoxia exposure on the offspring. Our findings reveal that preconception maternal hyperoxia exposure leads to growth retardation, cardiac insufficiency, and remodeling in both male and female offspring. Additionally, maternal pre-pregnancy hyperoxia exposure induces mitochondrial damage characterized by reduced oxidative phosphorylation, inhibited tricarboxylic acid (TCA) cycle, and decreased ATP production in the cardiac tissues of offspring mice. Supplementation of sodium propionate during lactation significantly improves growth retardation, mitigates metabolic remodeling, and partially restores cardiac function in hyperoxia-exposed offspring. In conclusion, our study suggests that maternal hyperoxia exposure before pregnancy leads to cardiac insufficiency in murine offspring. These findings may have important implications for mitigating maternal high oxygen toxicity on offspring development and disease risk, especially the cardiotoxic effects of hyperoxia on offspring development.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"133 ","pages":"Article 108864"},"PeriodicalIF":3.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474132","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":"Unveiling the transcriptional pattern of epithelial ovarian carcinoma-related microRNAs-mRNAs network after mouse exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin","authors":"Nour Aldeli , Abdulsamie Hanano","doi":"10.1016/j.reprotox.2025.108863","DOIUrl":"10.1016/j.reprotox.2025.108863","url":null,"abstract":"<div><div>2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), the most potent organic environmental contaminant known to date, is recognized as a human carcinogen. Despite the documented link between TCDD exposure and epithelial ovarian cancer (EOC) in mammalian females, the molecular mechanisms underlying cancer initiation remain elusive. Emerging evidence suggests aberrant miRNA expression in various human malignancies, including OC. This work was performed to examine whether TCDD exposure in female mice disrupts the expression of miRNAs, particularly those known as OC-modulators. We conducted an extensive search in the PubMed database to identify miRNAs experimentally implicated in OC. Fifty-two miRNAs were identified as potential OC modulators and classified into two groups based on their abundance in OC. Group I comprised 24 miRNAs upregulated in OC, while Group II included 28 miRNAs downregulated in OC. Subsequently, we analyzed the expression of both groups in BALB/c mice ovaries following a single TCDD dose. Our findings revealed significant upregulation of 10 miRNAs from Group I (miR-21, miR-27a, miR-30a, miR-99a, miR-141, miR-182, miR-183, miR-200a, miR-200b, and miR-429) and significant downregulation of 12 miRNAs from Group II (let-7d, miR-15a, miR-19a, miR-23b, miR-34a, miR-34c, miR-125b-1, miR-133, miR-140, miR-199a, miR-210, and miR-383) in TCDD-exposed mouse ovaries. Furthermore, we identified OC-related genes targeted by miRNAs from both groups through an extensive search in PubMed databases. Using TR-qPCR, we evaluated the downstream impact of TCDD-dysregulated miRNAs on their target genes. Our results indicate that TCDD-induced upregulation of oncogenic miRNAs negatively regulates target genes associated with EOC, while downregulation of cancer-suppressor miRNAs positively regulates genes linked to EOC.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108863"},"PeriodicalIF":3.3,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445585","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}
Youngin Jeong , Suil Son , Jiyun Park , C-Yoon Kim , Jin Kim
{"title":"Antidepressant aripiprazole induces adverse effects on neural development during cortex organoid generation","authors":"Youngin Jeong , Suil Son , Jiyun Park , C-Yoon Kim , Jin Kim","doi":"10.1016/j.reprotox.2025.108862","DOIUrl":"10.1016/j.reprotox.2025.108862","url":null,"abstract":"<div><div>A significant number of women experience anxiety and depressive symptoms during pregnancy, leading to the prescription of antidepressants, including aripiprazole. However, although a few animal studies have reported its developmental toxicity, there is a lack of research on the potential risks aripiprazole may pose to the fetus, particularly regarding neural development, as well as an absence of appropriate models to verify these effects. Therefore, this study investigates the impact of aripiprazole on neural development using cortex organoids, which can effectively model human brain development and function while overcoming interspecies differences. Cortex organoids were generated and exposed to aripiprazole at concentrations of 0.3–9 µM over 4 weeks. We assessed morphological changes, cell viability, gene expression, immunofluorescence staining, and electrophysiological function. The results revealed that aripiprazole led to significant reductions in organoid size and increased cell death, particularly at higher concentrations. Immunofluorescence analysis showed abnormalities in the expression patterns of neural stem cells and neuronal markers. Additionally, real-time PCR demonstrated decreased expression of genes related to neural stem cells, neural differentiation and migration, maturation, synaptogenesis, and gliogenesis, along with increased apoptosis-related gene expression. Electrophysiological recordings indicated impaired neural activity, evidenced by reduced mean firing rates. Our study is the first to demonstrate that aripiprazole induces adverse effects on neural development across functional, molecular, and morphological aspects. The findings will aid in a better understanding of the risks associated with antidepressant use during pregnancy in terms of neural development and suggest that cortex organoids are a valuable model for evaluating potential neurodevelopmental toxicants.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"133 ","pages":"Article 108862"},"PeriodicalIF":3.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459332","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 potential role of ascorbic acid in attenuating infertility induced by emamectin benzoate via suppressing oxidative stress and ameliorating sperm count in male rats","authors":"Assia Kamel-Chouider , Meriem Hariti , Samira Akdader-Oudahamne , Zohra Hamouli-Said","doi":"10.1016/j.reprotox.2025.108852","DOIUrl":"10.1016/j.reprotox.2025.108852","url":null,"abstract":"<div><div>Pesticides are chemical compounds with toxicological properties. Emamectin benzoate (EMB) is a macrolytic lactone belonging to the avermectin class, produced naturally by the actinomycetes <em>Streptomyces avermitilis</em>. Ascorbic acid (AA) is used in many therapeutic areas, in particular for its antioxidant properties. The objective of this study is to evaluate the potential role of ascorbic acid (AA) against the reproductive toxicity induced by emamectin benzoate (EMB). In this experimental study, 24 adult male rats were used. The animals were divided into 4 groups (n = 6). Control group (C) treated with distilled water, an EMB group received 20 mg EMB/kg body weight (bw) by gavage, AA group received ascorbic acid intraperitoneally (200 mg/kg bw) and an EMB + AA group received 20 mg EMB/kg bw and ascorbic acid intraperitoneally (200 mg/kg bw). The duration of the treatment was 15 days. Our results showed that the administration of EMB increased (MDA, proteins carbonyl), decreased antioxidant (SOD, CAT, GSH). Microscopic analysis revealed histological damage in the EMB group, which were represented by alteration of normal architecture, inflammatory cell infiltration, multifocal vacuolation of Sertoli cell cytoplasm, congested blood vessels, a large area of low spermatozoa density in epididymal lumen and increased collagen fibers in the muscle layer, which implicated fibrosis. However, co-treatment with ascorbic acid reduced EMB-related testis, epididymis toxicity, corrected the imbalance between oxidants and antioxidants, ameliorated sperm production, moderated amount of collagen fiber. We note that treatment with ascorbic acid (AA) only did not result in any significant change compared to controls. In conclusion, ascorbic acid has beneficial effects by attenuating the toxicity of Emamectin benzoate.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"133 ","pages":"Article 108852"},"PeriodicalIF":3.3,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441967","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":"Hormonal mechanism and pathogenetic therapy of citalopram-induced infertility in female rats","authors":"Ilhan Bahri Delibasi , Neset Gumusburun , Seval Bulut , Renad Mammadov , Betul Kalkan Yilmaz , Bahadir Suleyman , Nuri Bakan , Ali Sefa Mendil , Halis Suleyman , Durdu Altuner","doi":"10.1016/j.reprotox.2025.108859","DOIUrl":"10.1016/j.reprotox.2025.108859","url":null,"abstract":"<div><div>Citalopram is a selective serotonin reuptake inhibitor (SSRI) and has been associated with reproductive dysfunction in women. In this study, the effects of citalopram on reproductive health in female rats were investigated. Albino Wistar rats was divided into six groups (each group/n = 12): healthy (HG), citalopram (CTP), cabergoline (CBR), metyrapone (MTP), cabergoline+citalopram (CBR+CTP), and metyrapone+citalopram (MTP+CTP). Initially, cabergoline 0.1 mg/kg and metyrapone 50 mg/kg were administered orally. A dose of 10 mg/kg of citalopram was given orally one hour later. For 30 days, the treatment protocol was applied once a day. Then, blood samples were taken from the tail veins of six rats from each group for prolactin and corticosterone analyses and ovaries were removed after euthanasia. The ovaries were examined for oxidants and antioxidants and histopathologically. During two months, the remaining animals were kept with male rats. The rats that did not deliver during this period were considered infertile. In terms of oxidants and antioxidants, there was no significant difference between the groups (p > 0.05). In half of the female rats, citalopram caused infertility, increased levels of prolactin and corticosterone, and damaged the ovaries histopathologically (p < 0.05). Cabergoline suppressed the elevation of prolactin by citalopram (p < 0.001) but did not prevent infertility. In contrast, metyrapone significantly prevented the citalopram-induced increase in corticosterone, infertility, and tissue damage induced by citalopram (p < 0.05). According to the results of our study, the preventive effect of drugs that suppress excessive corticosterone on citalopram-induced infertility in rats may be encouraging for further clinical studies.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108859"},"PeriodicalIF":3.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433579","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 impact of triadimenol on male fertility: An in vitro study and molecular docking examination","authors":"Arici Merve , Bilgehan Ayşenur , Dincel Efe Dogukan , Özhan Gül","doi":"10.1016/j.reprotox.2025.108861","DOIUrl":"10.1016/j.reprotox.2025.108861","url":null,"abstract":"<div><div>Triadimenol, a triazole fungicide, induces various adverse effects including neurotoxicity, hepatotoxicity, and developmental/reproductive toxicity in non-target organisms. Occupational exposure generally occurs in male agricultural workers. Investigating the effects of triadimenol on three different testicular cell lines would be valuable in elucidating the mechanisms underlying male reproductive issues or infertility. This preliminary study examines the potential toxic effects of triadimenol exposure in Leydig (TM3), Sertoli (TM4), and mouse-derived Spermatogonia (GC-1) cell lines, which are representative of the male reproductive system <em>in vitro.</em> The median inhibitory concentration (IC<sub>50</sub>) values of triadimenol were found to be 121.35 μM, 332.1 μM, and 349.49 μM in TM3, TM4, and GC-1 cells, respectively. The exposure doses were determined to range from 0 to 100 µM in TM3 cell line and 0–300 µM in TM4 and GC-1 cell lines. Reactive oxygen species (ROS) production, reduced glutathione (GSH) content, malondialdehyde (MDA) and protein carbonyl levels, and genotoxicity were examined. TM3 cell line was more resistant to oxidative damage than the other cell lines, while TM4 cell line was found to be more sensitive in terms of protein carbonyl formation. Triadimenol damaged DNA in TM3 cell line (≥16.93), TM4 cell line (≥9.18), and GC-1 cell line (≥3.28). Additionally, the docking score of triadimenol on the active site of steroid 5-α-reductase 2 (5αR2), which converts testosterone to 5α-dihydrotestosterone, was not close. The results emphasised that the toxicity of triadimenol was cell-specific. Overall, triadimenol disrupted male fertility by affecting spermatogenesis, testosterone production, germ cell support, and sperm quality.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108861"},"PeriodicalIF":3.3,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143422400","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}