Chongshan Dai , Zhihui Hao , Dingkuo Liu , Zhanhui Wang , Gea Oliveri Conti , Tony Velkov , Jianzhong Shen
{"title":"哺乳动物暴露与脱氧雪腐镰刀菌醇相关的雄性生殖毒性:分子机制、解毒和未来方向","authors":"Chongshan Dai , Zhihui Hao , Dingkuo Liu , Zhanhui Wang , Gea Oliveri Conti , Tony Velkov , Jianzhong Shen","doi":"10.1016/j.envint.2025.109478","DOIUrl":null,"url":null,"abstract":"<div><div>An increasing body of evidence indicates that exposure to widespread, environmental and food contaminants such as mycotoxins may cause endocrine disorders and infertility. Deoxynivalenol (DON), which is a toxic secondary metabolite produced by <em>Fusarium</em> fungi, can lead to multiple harmful effects in humans and animals, such as hepatotoxicity, nephrotoxicity, immunotoxicity, gastrointestinal toxicity, neurotoxicity, genetic toxicity and carcinogenicity. Recently, there has been growing concern about DON-induced male infertility. Exposure to DON and its metabolites can damage the structure and function of male reproductive organs, resulting in impairment of gametogenesis and thus impaired fertility. Potential molecular mechanisms involve oxidative stress, inflammatory response, mitochondrial dysfunction, apoptosis, cell cycle arrest, pyroptosis, and ferroptosis. Moreover, several signaling pathways, including nuclear factor-kappa B, mitogen−activated protein kinase, NLR family pyrin domain containing 3, nuclear factor erythroid 2-related factor 2, AMP-activated protein kinase, mitochondrial apoptotic pathways, and microRNAs are involved in these detrimental biological processes. Research has shown that several antioxidants, small-molecule inhibitors, or proteins (such as lactoferrin) supplementation can potentially offer protective effects by targeting these signaling pathways. This review comprehensively summarizes the harmful effects of DON exposure on male reproductive function in mammals, the underlying molecular mechanisms and emphasizes the potential of several small molecules as protective therapeutics. In the further, the systematic risk assessment when DON at environmental exposure doses to human reproductive health, the in-depth and precise molecular mechanism investigation using emerging technologies, and the development of more effective intervention strategies warrant urgent investigation.</div></div>","PeriodicalId":308,"journal":{"name":"Environment International","volume":"199 ","pages":"Article 109478"},"PeriodicalIF":10.3000,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Deoxynivalenol exposure-related male reproductive toxicity in mammals: Molecular mechanisms, detoxification and future directions\",\"authors\":\"Chongshan Dai , Zhihui Hao , Dingkuo Liu , Zhanhui Wang , Gea Oliveri Conti , Tony Velkov , Jianzhong Shen\",\"doi\":\"10.1016/j.envint.2025.109478\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>An increasing body of evidence indicates that exposure to widespread, environmental and food contaminants such as mycotoxins may cause endocrine disorders and infertility. Deoxynivalenol (DON), which is a toxic secondary metabolite produced by <em>Fusarium</em> fungi, can lead to multiple harmful effects in humans and animals, such as hepatotoxicity, nephrotoxicity, immunotoxicity, gastrointestinal toxicity, neurotoxicity, genetic toxicity and carcinogenicity. Recently, there has been growing concern about DON-induced male infertility. Exposure to DON and its metabolites can damage the structure and function of male reproductive organs, resulting in impairment of gametogenesis and thus impaired fertility. Potential molecular mechanisms involve oxidative stress, inflammatory response, mitochondrial dysfunction, apoptosis, cell cycle arrest, pyroptosis, and ferroptosis. Moreover, several signaling pathways, including nuclear factor-kappa B, mitogen−activated protein kinase, NLR family pyrin domain containing 3, nuclear factor erythroid 2-related factor 2, AMP-activated protein kinase, mitochondrial apoptotic pathways, and microRNAs are involved in these detrimental biological processes. Research has shown that several antioxidants, small-molecule inhibitors, or proteins (such as lactoferrin) supplementation can potentially offer protective effects by targeting these signaling pathways. This review comprehensively summarizes the harmful effects of DON exposure on male reproductive function in mammals, the underlying molecular mechanisms and emphasizes the potential of several small molecules as protective therapeutics. In the further, the systematic risk assessment when DON at environmental exposure doses to human reproductive health, the in-depth and precise molecular mechanism investigation using emerging technologies, and the development of more effective intervention strategies warrant urgent investigation.</div></div>\",\"PeriodicalId\":308,\"journal\":{\"name\":\"Environment International\",\"volume\":\"199 \",\"pages\":\"Article 109478\"},\"PeriodicalIF\":10.3000,\"publicationDate\":\"2025-04-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Environment International\",\"FirstCategoryId\":\"93\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0160412025002296\",\"RegionNum\":1,\"RegionCategory\":\"环境科学与生态学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENVIRONMENTAL SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Environment International","FirstCategoryId":"93","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0160412025002296","RegionNum":1,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENVIRONMENTAL SCIENCES","Score":null,"Total":0}
Deoxynivalenol exposure-related male reproductive toxicity in mammals: Molecular mechanisms, detoxification and future directions
An increasing body of evidence indicates that exposure to widespread, environmental and food contaminants such as mycotoxins may cause endocrine disorders and infertility. Deoxynivalenol (DON), which is a toxic secondary metabolite produced by Fusarium fungi, can lead to multiple harmful effects in humans and animals, such as hepatotoxicity, nephrotoxicity, immunotoxicity, gastrointestinal toxicity, neurotoxicity, genetic toxicity and carcinogenicity. Recently, there has been growing concern about DON-induced male infertility. Exposure to DON and its metabolites can damage the structure and function of male reproductive organs, resulting in impairment of gametogenesis and thus impaired fertility. Potential molecular mechanisms involve oxidative stress, inflammatory response, mitochondrial dysfunction, apoptosis, cell cycle arrest, pyroptosis, and ferroptosis. Moreover, several signaling pathways, including nuclear factor-kappa B, mitogen−activated protein kinase, NLR family pyrin domain containing 3, nuclear factor erythroid 2-related factor 2, AMP-activated protein kinase, mitochondrial apoptotic pathways, and microRNAs are involved in these detrimental biological processes. Research has shown that several antioxidants, small-molecule inhibitors, or proteins (such as lactoferrin) supplementation can potentially offer protective effects by targeting these signaling pathways. This review comprehensively summarizes the harmful effects of DON exposure on male reproductive function in mammals, the underlying molecular mechanisms and emphasizes the potential of several small molecules as protective therapeutics. In the further, the systematic risk assessment when DON at environmental exposure doses to human reproductive health, the in-depth and precise molecular mechanism investigation using emerging technologies, and the development of more effective intervention strategies warrant urgent investigation.
期刊介绍:
Environmental Health publishes manuscripts focusing on critical aspects of environmental and occupational medicine, including studies in toxicology and epidemiology, to illuminate the human health implications of exposure to environmental hazards. The journal adopts an open-access model and practices open peer review.
It caters to scientists and practitioners across all environmental science domains, directly or indirectly impacting human health and well-being. With a commitment to enhancing the prevention of environmentally-related health risks, Environmental Health serves as a public health journal for the community and scientists engaged in matters of public health significance concerning the environment.