Role of Reactive Oxygen Species in Male Infertility

Paick, Jae Seung

Abstract

Reactive oxygen species (ROS), highly reactive oxygen free radicals, are an inherent byproduct of aerobic life. In the male genital tract, ROS are generated by spermatozoa and leukocytes. Although the controlled generation of ROS may have diverse physiologic functions such as capacitation and the acrosome reaction, uncontrolled production is considered important in defective sperm function and infertility. In the normal fertile man, to meet this increased ROS challenge, there are sufficient antioxidant mechanisms to protect sperm from oxidative injury. The imbalance between ROS production and the total antioxidant capacity in seminal fluid indicates oxidative stress and correlates with male infertility. As plasma membranes of spermatozoa are rich in polyunsaturated fatty acids and there are low concentrations of scavenging enzymes within the cytoplasm, the membranes are susceptible to ROS-induced lipid peroxidation. Lipid peroxidation involves two steps: (1) initiation by superoxide or H2O2 amplified by the Haber-Weiss and Fenton reactions; and (2) propagation, which occurs in the presence of transition-metal ions. Various causes of infertility are associated with excessive ROS production and a decrease in ROS scavenging activity. Especially, some sperm preparation methods used in assisted-reproduction techniques contribute to a decrease in ROS scavenging activities. The methods used in the measurement of ROS in the male genital tract are not satisfactory because of the difficulty of determining the site of generation and because the effects of ROS are short lived. As there are many unresolved questions concerning the exact role of ROS as a cause of infertility, commercial claims of the benefits of antioxidant supplements for fertility improvement must be viewed cautiously until properly designed multicenter clinical trials are completed. From the current data, it appears that no single adjuvant will be able to enhance the fertilizing capacity of infertile men.