Significance of oxidative stress and sperm chromatin damage in male infertility

Abstract Researchers studying the causes of male infertility have recently focused on the role played by reactive oxygen species (ROS)-a highly reactive oxidizing agent belonging to the class of free radicals. ROS are produced by a variety of semen components, and antioxidants in the seminal fluid keep their levels in check. Small amounts of ROS help spermatozoa acquire their necessary fertilizing capabilities. However, when ROS production exceeds the scavenging capacity of the antioxidants-a state referred to as oxidative stress (OS)-ROS become toxic to sperm. Research suggests that ROS attack the integrity of DNA in the sperm nucleus by causing base modification, DNA strand breaks, and chromatin cross-linking. DNA damage induced by excessive levels of ROS may accelerate the process of germ cell apoptosis, leading to the decline in sperm counts associated with male infertility. This chapter will discuss in more detail the cellular origins of ROS in human semen, how ROS damages sperm nuclear DNA, and how such DNA damage contributes to male infertility. Research highlights from the Cleveland Clinic, including the novel ROS-TAC (ROS total antioxidant capacity) score for assessing OS, will also be presented