Deoxynivalenol exposure-related male reproductive toxicity in mammals: Molecular mechanisms, detoxification and future directions

Abstract

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.