Dai Chongshan, Hao Zhihui, Liu Dingkuo, Wang Zhanhui, Conti Gea Oliveri, Velkov Tony, Shen Jianzhong
National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; Technology Innovation Center for Food Safety Surveillance and Detection (Hainan), Sanya Institute of China Agricultural University, Sanya 572025, China.
National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; Technology Innovation Center for Food Safety Surveillance and Detection (Hainan), Sanya Institute of China Agricultural University, Sanya 572025, China.
Environ Int. 2025 May;199:109478. doi: 10.1016/j.envint.2025.109478. Epub 2025 Apr 17.
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.
越来越多的证据表明，接触广泛存在的环境和食物污染物，如霉菌毒素，可能会导致内分泌紊乱和不育。脱氧雪腐镰刀菌烯醇（DON）是镰刀菌产生的一种有毒次级代谢产物，可对人和动物产生多种有害影响，如肝毒性、肾毒性、免疫毒性、胃肠道毒性、神经毒性、遗传毒性和致癌性。最近，人们越来越关注DON引起的男性不育。接触DON及其代谢产物会损害男性生殖器官的结构和功能，导致配子发生受损，从而损害生育能力。潜在的分子机制包括氧化应激、炎症反应、线粒体功能障碍、细胞凋亡、细胞周期停滞、焦亡和铁死亡。此外，包括核因子-κB、丝裂原活化蛋白激酶、含NLR家族pyrin结构域3、核因子红细胞2相关因子2、AMP活化蛋白激酶、线粒体凋亡途径和微小RNA在内的几种信号通路参与了这些有害的生物学过程。研究表明，补充几种抗氧化剂、小分子抑制剂或蛋白质（如乳铁蛋白）可能通过靶向这些信号通路提供保护作用。本综述全面总结了DON暴露对哺乳动物雄性生殖功能的有害影响、潜在的分子机制，并强调了几种小分子作为保护性治疗药物的潜力。进一步而言，对环境暴露剂量的DON对人类生殖健康的系统风险评估、利用新兴技术进行深入精确的分子机制研究以及开发更有效的干预策略都亟待开展。
