Role of the reactive oxygen species induced DNA damage in human spermatozoa dysfunction

Abstract

Non-enzymatic oxidative damage of DNA in the male germ cell line is believed to be one of the key mechanisms of premature apoptosis of spermatozoa and in pathogenesis of male subfertility. High motility of sperm cells requires high activity of energetic metabolism and mitochondrial functioning that makes them subject to excessive influence of reactive oxygen species (ROS). Low volume of cytoplasm, where antioxidative enzymes, such as glutathione peroxidase (GPx), catalase and superoxide dismutase work, complicates the delivery of antioxidants into different compartments of a spermatozoon. Hence, the protection of sperm against oxidative stress is provided mostly by antioxidants produced by male reproductive tract and antioxidative machinery of the oocyte. The lifespan of sperm cells is to a significant degree regulated by Ras dependent cell signaling pathways, such as phosphatidylinositol 3-kinase (PI3K)/Akt. Factors, inducing oxidative stress in human spermatozoa and their regulation mechanisms are discussed.