Reproductive toxicology最新文献

{"title":"Epididymal toxicity of deoxynivalenol: Age-specific effects in prepubertal and adult mice","authors":"Ana Laura Paulino Leite Gomes ,&nbsp;Juliana Rubira Gerez ,&nbsp;Marielen de Souza ,&nbsp;Rafaela Pires Erthal ,&nbsp;Dayane Priscila dos Santos ,&nbsp;Camila Rodrigues Ferraz ,&nbsp;Waldiceu A. Verri ,&nbsp;Glaura Scantamburlo Alves Fernandes ,&nbsp;Ana Paula Frederico Rodrigues Loureiro Bracarense","doi":"10.1016/j.reprotox.2025.109116","DOIUrl":"10.1016/j.reprotox.2025.109116","url":null,"abstract":"<div><div>Deoxynivalenol (DON), a mycotoxin produced by <em>Fusarium</em> species that contaminates agricultural commodities worldwide, is known for its deleterious effects on male reproduction. Although hormonal, testicular, and sperm alterations have been described, the effects of DON on the epididymis, an organ essential for sperm maturation and storage, remain underexplored. This study evaluated DON-induced epididymal toxicity in prepubertal and adult mice. Sixty animals were fed a DON-contaminated diet (10 mg DON/kg feed) or a mycotoxin-free diet for 15 or 28 days, respectively. Stereological, histological, and immunohistochemical (E-cadherin, caspase-3, and androgen receptor) analyses were conducted, together with assessments of oxidative stress, inflammatory profile, sperm count, and transit time. In prepubertal mice, DON exposure altered epididymal compartment proportions, increasing stromal areas in the caput and cauda, expanding the cauda epithelium, and reducing luminal spaces. Histological changes included an increased number of tubules without sperm and interstitial fibrosis, accompanied by decreased FRAP levels and reduced macrophage number, TNF-α, and IL-1β expression. In adult mice, DON reduced stromal area in the caput, increased stromal and decreased luminal compartments in the cauda, and induced epithelial vacuolization, fibrosis, and apoptosis, along with reduced TNF-α levels. These findings demonstrate that DON disrupts epididymal development in prepubertal mice; however, longitudinal studies are required to evaluate its long-term consequences. In adults, DON may impair fertility through tissue remodeling and inflammatory modulation. The observed reduction in pro-inflammatory mediators may represent a potential therapeutic pathway; however, further studies are required to clarify the reproductive risks and mechanisms underlying DON exposure.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"139 ","pages":"Article 109116"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145588633","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 ameliorative effect of curcumin nanoemulsion on busulfan-induced testicular toxicity in adult rat model","authors":"Sarah E. Amin ,&nbsp;Eman F. Farghaly ,&nbsp;Doaa A. Abdelmonsif ,&nbsp;Eiman I. Zaki ,&nbsp;Walaa Omar","doi":"10.1016/j.reprotox.2025.109106","DOIUrl":"10.1016/j.reprotox.2025.109106","url":null,"abstract":"<div><div>Many factors contribute to infertility. Among these are chemotherapeutic drugs as they interfere with cell division and spermatogenesis. Busulfan (BU) is one of these drugs that is applied in the treatment of many malignancies. Latest studies have focused on the protective impact of medicinal plant products, such as curcumin (CU), for ameliorating tissue damage through their antioxidant properties. Nanoparticles are now used to improve drug delivery and efficacy. Our study was aimed at assessing the potential therapeutic effect of curcumin nanoemulsion (CU-NE) on busulfan-induced testicular toxicity in adult rats. Forty-eight adult male albino rats were randomly distributed in six groups, 8 rats each: Control groups; group I: negative control, II: vehicle control, III: CU-NE. Group IV: BU, group V: CU-NE+BU and group VI: spontaneous recovery. Each group was assessed regarding serum level of testosterone, tumor necrosis factor-α (TNF-α) and total antioxidant capacity (TAC). Malondialdehyde (MDA) and glutathione peroxidase (GPX) levels were measured in testicular tissue. Moreover, sperm parameters were measured, and histological examination of the testis was performed. CU-NE significantly improved all the tested parameters and ameliorated the degenerative changes found in the testis following busulfan administration. Thus, CU-NE could be a promising therapeutic agent that restores spermatogenesis and facilitates regeneration of the seminiferous epithelium after chemotherapy-induced testicular damage.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"139 ","pages":"Article 109106"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145506496","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":"Folic acid alleviates fetal growth restriction induced by gestational Di (2-ethylhexyl) phthalate exposure in mice through activating the STAT3/HIF-1α/VEGFA signaling pathway","authors":"Fang Xie ,&nbsp;Mengzhen Hou ,&nbsp;Yingxia Wang ,&nbsp;Xutao Ling ,&nbsp;Yun Yu ,&nbsp;Qianqian Huang ,&nbsp;Lun Zhang ,&nbsp;Cheng Zhang ,&nbsp;Jun Yu ,&nbsp;Jianqing Wang","doi":"10.1016/j.reprotox.2025.109109","DOIUrl":"10.1016/j.reprotox.2025.109109","url":null,"abstract":"<div><div>Di(2-ethylhexyl) phthalate (DEHP), a ubiquitous environmental pollutant, is extensively utilized in industrial, medical, and food-related applications. In our previous study, we successfully established an mice model of ICP induced by gestational di(2-ethylhexyl) phthalate (DEHP) exposure. Our findings suggested that DEHP-induced folic acid (FA) deficiency might contribute to the development of IUGR. However, the potential protective effects of FA supplementation against IUGR resulting from gestational DEHP exposure remain to be elucidated. Notably, administration of DEHP to pregnant mice resulted in a significant reduction in average placental weight and diameter, as well as fetal body weight and crown-rump length. Histological analysis using H&amp;E staining and immunohistochemistry revealed a reduction in the area of placental blood sinuses and the density of CD34⁺ micro vessels. Gene expression analysis of placental nutrient transporters demonstrated significant downregulation of glucose transporter Glut1, fatty acid transporters CD36 and Fatp1, as well as amino acid transporter Snat4. Molecular docking analysis indicated that FA exhibited strong binding affinity toward the target protein STAT3. Experimental findings confirmed that FA could enhance placental angiogenesis and alleviate placental hypoplasia and nutrient transport impairments by activating the STAT3/HIF-1α/VEGFA signaling pathway, thus preventing IUGR caused by maternal DEHP exposure. These results provide a theoretical foundation for the prevention and treatment of ICP-associated IUGR.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"139 ","pages":"Article 109109"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534261","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":"Shared and compound-specific pathways of bisphenol A and its analogues in male infertility: An integrative approach combining network toxicology, omics analysis, and molecular docking","authors":"Jiahao Xu ,&nbsp;Yanhui Hu ,&nbsp;Zhilei Mao ,&nbsp;Kun Zhou","doi":"10.1016/j.reprotox.2025.109100","DOIUrl":"10.1016/j.reprotox.2025.109100","url":null,"abstract":"<div><div>This study aimed to elucidate the potential mechanisms by which common bisphenols (BPs) contribute to male infertility. Five representative BPs (BPA, BPS, BPF, BPAF, TBBPA) were analyzed using an integrated strategy combining network toxicology, omics analysis (via GEO and TCGA datasets), literature review and molecular docking. Predicted BP targets from SwissTargetPrediction and TargetNet were intersected with male infertility-related genes from GeneCards. Overlapping targets underwent protein–protein interaction (PPI) network construction and enrichment analysis. Core target expression was analyzed using GEO and TCGA databases and literature review. Core targets were docked with BPs, followed by 100 ns MD simulations and MM/PBSA binding free energy decomposition. Eleven potential common targets were identified, which were enriched in the apoptotic signaling pathway, mitochondrial membrane permeability regulation, and steroid hormone biosynthesis. Four core targets—PTGS2, BCL2, AR, and CYP19A1—showed high connectivity. TCGA analysis demonstrated significant downregulation of PTGS2 and CYP19A1 in seminoma. Literature evidence showed consistent BCL2 suppression across BPs, AR inhibition by BPA, BPS, and TBBPA, CYP19A1 upregulation by BPA and BPAF, and PTGS2 upregulation by BPA. TBBPA-PTGS2 and BPA-AR complexes exhibited the strongest and most stable binding, dominated by van der Waals forces, whereas the BPAF-CYP19A1 complex showed strong electrostatic attraction, offset by polar solvation. BPs may impair male fertility through shared BCL2-mediated apoptosis, with computational evidence suggesting compound-specific pathways involving CYP19A1 (steroidogenesis), AR (androgen signaling), and PTGS2 (inflammation). These findings underscore the need for compound-specific toxicological assessments integrating mechanistic and computational evidence to guide precise prevention and regulatory strategies.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"139 ","pages":"Article 109100"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145435521","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":"Nanodrug impact on female reproductive health and fetal development: From translation approaches to long-term safety concern","authors":"Karmveer Yadav ,&nbsp;Ritu Sharma","doi":"10.1016/j.reprotox.2025.109103","DOIUrl":"10.1016/j.reprotox.2025.109103","url":null,"abstract":"<div><div>Biomaterials for drug delivery offer significant advantages over conventional medications, including enhanced cellular uptake, improved drug stability, targeted delivery, and controlled drug release. Cutting-edge nanodrugs delivery approaches such as drugs formulations, hydrogels, films, and vaccines have been developed for diverse applications, including hormonal therapies, immunotherapy, infectious diseases, and gestational health. Tailored biomaterial systems can administer drugs for conditions such as vaginal infections, endometriosis, pregnancy disorders, reproductive cancers, and inherent messes during gestation. Designing delivery technologies for female health requires addressing unique barriers and challenges specific to the female body. Advancements in delivery technologies in other disease contexts can inform innovations in female health treatments. Delivering biomaterials and medications at the time of pregnancy may have adverse developmental consequences for the fetus, necessitating an understanding of how nanomaterials interact with reproductive systems and activate signal transduction pathways. Ensuring safety and minimizing toxicity are critical considerations, alongside developing appropriate and accessible preclinical models to facilitate clinical translation. Omics-based techniques can aid in the sustainable risk assessment and safety evaluation of nanomaterials by identifying biomolecules involved in nanotoxicity. Taking these events or exposures together with their toxicity on the female reproductive system and offspring outcomes, thus further study is required to explore, the way that nanoparticles compromise fertility and growth of embryos in humans. Long-term studies are crucial for assessing the safety of nanodrugs in pregnant female, especially concerning chronic effects from prenatal exposure. Effective development and translation of nano-drug delivery technologies for female health require collaboration among biomaterials researchers, patients, clinicians, and regulatory agencies.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"139 ","pages":"Article 109103"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145469138","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 pragmatic upstream network for disrupted steroidogenesis through reduced enzyme activity and steroid hormone production for Adverse Outcome Pathway building","authors":"Nora Bouftas ,&nbsp;Anna K. Rosenmai ,&nbsp;Eleftheria M. Panagiotou ,&nbsp;Johanna Zilliacus ,&nbsp;Pauliina Damdimopoulou ,&nbsp;Anna Beronius ,&nbsp;Majorie van Duursen ,&nbsp;Terje Svingen","doi":"10.1016/j.reprotox.2025.109105","DOIUrl":"10.1016/j.reprotox.2025.109105","url":null,"abstract":"<div><div>The Adverse Outcome Pathway (AOP) framework offers a structured approach to organize mechanistic knowledge of toxicological pathways. By describing biological events linking molecular initiating events (MIEs) to an adverse outcome (AO) at the organismal level, it aims to aid regulatory decision-making through predictive toxicology approaches. To serve this purpose, however, it is recognized that AOP networks are required to adequately capture complex biology. Another central feature of the AOP concept is that upstream molecular networks will be shared between numerous downstream AOs. This report focuses on steroidogenesis, a common target of endocrine disrupting chemicals, and the development of an upstream network for reduced steroidogenesis focusing on hormones and enzymes that are particularly relevant to mammalian reproduction. The AOP-Wiki was mapped for existing content related to steroidogenesis and the resulting network expanded by incorporating additional key events (KEs) and KE Relationships (KERs) not yet inventoried. All existing KEs and KERs were evaluated for completeness. Using a pragmatic approach, we developed the identified KEs and KERs by integrating evidence from recent review articles. The focus was particularly on the impact of disrupted cholesterol transport, altered enzyme activities and hormone levels. The resulting upstream AOP network serves as a foundation for developing complete AOPs linking disrupted steroidogenesis with downstream AOs. This upstream network will also contribute to identifying relevant test assays for development and understanding the predictive capabilities of existing in vitro assays, such as the OECD-validated H295R steroidogenesis assay.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"139 ","pages":"Article 109105"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145469139","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":"Polystyrene nanoparticles induced adverse pregnancy outcomes via the activation of placental ferroptosis and gut microbiota dysfunction","authors":"Zhilong He ,&nbsp;Jijiao Cai ,&nbsp;Ruitong Liu ,&nbsp;Weici Yan ,&nbsp;Guoqi Yang ,&nbsp;Runxiong Yu ,&nbsp;Lili Xin ,&nbsp;Zhongxiao Wan","doi":"10.1016/j.reprotox.2025.109113","DOIUrl":"10.1016/j.reprotox.2025.109113","url":null,"abstract":"<div><div>Maternal exposure to microplastics, particularly polystyrene nanoparticles (PS-NPs), is an emerging environmental threat associated with adverse pregnancy outcomes. However, the underlying mechanisms, especially the potential involvement of placental ferroptosis and gut microbiota, remain largely unexplored. This study aimed to elucidate whether and how maternal exposure to 50-nm PS-NPs disrupts pregnancy in a mouse model, with a focus on gut microbiota dysbiosis and placental ferroptosis. We found that PS-NPs exposure during pre-mating and gestation induced gut microbiota dysbiosis (e.g., increased <em>Campylobacterota</em> and <em>Helicobacter</em>) and triggered placental ferroptosis, as evidenced by iron accumulation, lipid peroxidation, and dysregulation of key proteins associated with ferroptosis. These cellular disruptions led to impaired placental barrier function, increased inflammation, and ultimately, adverse pregnancy outcomes, including elevated embryo resorption and reduced fetal weight. Crucially, correlation analysis linked specific gut microbiota alterations to ferroptosis and pregnancy loss. Furthermore, <em>in vitro</em> experiments confirmed that ferroptosis inhibitors alleviated PS-NPs-induced trophoblast dysfunction. These results suggest that maternal exposure to PS‑NPs may contribute to adverse pregnancy outcomes via inducing gut‑microbiota dysbiosis and placental ferroptosis, which might be potential focus for future mechanistic and therapeutic investigations.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"139 ","pages":"Article 109113"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145565078","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":"Comparison of steroidogenic disruption in adrenal H295R and ovarian KGN and COV434 cell models and the implications to assess female reproductive toxicity","authors":"Paraskevi Vazakidou ,&nbsp;Charlotte Koopmans ,&nbsp;Sandra Nijmeijer ,&nbsp;Laetitia L. Lecante ,&nbsp;Peng Liu ,&nbsp;Séverine Mazaud-Guittot ,&nbsp;Paul A. Fowler ,&nbsp;Pim E.G. Leonards ,&nbsp;Majorie B.M. van Duursen","doi":"10.1016/j.reprotox.2025.109088","DOIUrl":"10.1016/j.reprotox.2025.109088","url":null,"abstract":"<div><div>To investigate the need for an ovarian-specific steroidogenesis assay in regulatory testing, steroid hormone profiles from adrenal H295R and ovarian KGN and COV434 cell cultures were compared with primary human cultures using LC-MS/MS. Hierarchical clustering showed close similarity between steroid hormone profiles of H295R and human fetal adrenal and ovarian tissue cultures, while KGN and COV434-derived profiles closer resembled human adult ovarian profiles. COV434 cultures showed the lowest number of steroid hormones even after forskolin stimulation. Specifically, in vehicle-treated controls 17 out of 21 steroid hormones were quantified in H295R cultures, 10 in KGN cultures and 7 in COV434 cultures. These included three backdoor pathway steroids, which were detected in different levels in the three cell cultures. Reference chemicals for steroidogenic disruption showed different effects in the cell lines, with most striking results early in the steroidogenic pathway. Atrazine, ketoconazole and aminoglutethimide affected pregnenolone and progesterone concentrations in KGN cultures more potently than in H295R cultures. Ketoconazole and propylparaben increased progesterone levels in H295R, but decreased levels in KGN cultures. Despite the differences in responses, classification of the test chemicals to act as steroidogenic disruptors was similar in H295R and KGN cell lines, but only when the OECD criteria were applied to a broad steroidome. These data do not support the use of KGN cells as an ovarian-specific steroidogenesis assay in a regulatory context, but do support the inclusion of more steroid hormones in the current test guideline to enhance the information that can be retrieved from the H295R assay.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"139 ","pages":"Article 109088"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145422128","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":"Heavy metals and human reproductive toxicity: Mechanisms, pregnancy outcomes, and mitigation strategies","authors":"Greta Marconi ,&nbsp;Chiara Di Resta ,&nbsp;Assunta Naclerio ,&nbsp;Giuseppe Banfi ,&nbsp;Rossella Tomaiuolo","doi":"10.1016/j.reprotox.2025.109104","DOIUrl":"10.1016/j.reprotox.2025.109104","url":null,"abstract":"<div><div>Heavy metals are environmental pollutants with well-documented systemic toxicity. Emerging evidence highlights their detrimental effects on human reproductive health. This narrative review aims to synthesize current scientific literature on the reproductive toxicity of arsenic (As), cadmium (Cd), chromium (Cr), mercury (Hg), and lead (Pb), focusing on their impact on fertility, pregnancy outcomes, fetal development, and neonatal health. The analysis includes cellular, molecular, and endocrine mechanisms, and considers both chronic environmental and acute occupational exposures. Inclusion criteria comprised peer-reviewed experimental, clinical, and review studies involving human subjects, providing direct translational relevance. Key endpoints included gametogenesis, hormonal regulation, fertility outcomes, and pregnancy complications. The main mechanisms of heavy metal-induced reproductive toxicity include DNA damage, oxidative stress, apoptosis, ionic mimicry, and hormonal disruption. In males, exposure is associated with reduced sperm quality, altered morphology, and impaired motility. In females, heavy metals interfere with oocyte maturation, ovarian function, and hormonal balance, increasing the risk of infertility, miscarriage, and adverse pregnancy outcomes. In addition to summarizing toxic effects, the review also discusses emerging protective and mitigation strategies—such as micronutrient and antioxidant supplementation—that may counteract reproductive damage. Heavy metal exposure, even at low levels, poses a significant risk to human reproductive health. The findings underscore the urgent need for preventive strategies, environmental regulation, and targeted health monitoring, particularly among vulnerable populations. Future research should explore the long-term and transgenerational effects of exposure.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"139 ","pages":"Article 109104"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145469140","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":"Inulin attenuates reproductive toxicity caused by prenatal and lactation GenX exposure through modulating the hypothalamic–pituitary–testicular (HPT) axis via the LH/cAMP/StAR pathway in male mice","authors":"Ya-Qi Chen ,&nbsp;Yu-Kui Chen ,&nbsp;Jin-Jin Zhang ,&nbsp;Qin-Yao Zhang ,&nbsp;Yu Liu ,&nbsp;Ji-Hong Wang ,&nbsp;Qi Wang ,&nbsp;Xiao-Li Xie","doi":"10.1016/j.reprotox.2025.109065","DOIUrl":"10.1016/j.reprotox.2025.109065","url":null,"abstract":"<div><div>With persistent and bioaccumulation concerns, hexafluoropropylene oxide dimer acid (HFPO-DA or GenX) has been detected in surface water, plants, and biota. However, its male reproductive toxicity is poorly understood. In this study, pregnant 8-week-old C57BL/6 J female mice (n = 36) were administered Milli-Q water, GenX (2 mg/kg/day), GenX with inulin (5 g/kg/day) or inulin by gavage until weaning (PND28) to evaluate the effects on the reproductive function of the male offspring. Early-life GenX exposure resulted in decreased sperm quality, impaired testicular tissue structure, and reduced serum testosterone and luteinizing hormone (LH) levels in male mice (<em>p</em> &lt; 0.05), suggesting reproductive toxicity and disturbance of the hypothalamic<img>pituitary<img>testicular axis. Consistent with the enrichment of the cAMP pathway shown by transcriptomics analysis, decreased protein expression of StAR, CYP11A1, CYP17A1, 3β-HSD, 17β-HSD and PKA (<em>p</em> &lt; 0.05) and overexpression of NPY (<em>p</em> &lt; 0.05) were also detected in the GenX group. Inulin alleviated testicular structure injury resulting from GenX exposure and increased serum testosterone and LH levels as well as protein expression in the cAMP pathway. Taken together, our results suggest that prenatal and lactation GenX exposure reduces testosterone synthesis in male mice by modulating the LH-mediated cAMP pathway, leading to male reproductive disorders, whereas inulin intervention might attenuate reproductive toxicity.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"138 ","pages":"Article 109065"},"PeriodicalIF":2.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092490","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}