Infertile men have higher levels of semen reactive oxygen species (ROS) than do fertile men. High levels of semen ROS can cause sperm dysfunction, sperm DNA damage and reduced male reproductive potential. This observation has led clinicians to treat infertile men with antioxidant supplements. The purpose of this article is to discuss the rationale for antioxidant therapy in infertile men and to evaluate the data on the efficacy of dietary and in vitro antioxidant preparations on sperm function and DNA damage. To date, most clinical studies suggest that dietary antioxidant supplements are beneficial in terms of improving sperm function and DNA integrity. However, the exact mechanism of action of dietary antioxidants and the optimal dietary supplement have not been established. Moreover, most of the clinical studies are small and few have evaluated pregnancy rates. A beneficial effect of in vitro antioxidant supplements in protecting spermatozoa from exogenous oxidants has been demonstrated in most studies; however, the effect of these antioxidants in protecting sperm from endogenous ROS, gentle sperm processing and cryopreservation has not been established conclusively. Keywords: antioxidant; male infertility; oxidative stress; sperm DNA fragmentation; vitamins RELATIONSHIP BETWEEN OXIDATIVE STRESS AND SPERM DYSFUNCTION Seminal oxidative stress (OS) results from an imbalance between reactive oxygen species (ROS) production and ROS scavenging by seminal antioxidants. Seminal OS is believed to be one of the main factors in the pathogenesis of sperm dysfunction and sperm DNA damage in male infertility.1-4 Indeed, it is estimated that 25% of infertile men possess high levels of semen ROS, whereas fertile men do not have high levels of semen ROS.1,4-6 Although a controlled production of these ROS is required for sperm physiology (sperm hyperactivation, capacitation and acrosome reaction) and for natural fertilization, [7][8][9] the excessive production of ROS by immature germ cells and leukocytes causes sperm dysfunction (lipid peroxidation, loss of motility and sperm DNA damage). 9,10 Spermatozoa are particularly susceptible to oxidative injury due to the abundance of plasma membrane polyunsaturated fatty acids. [10][11][12] These unsaturated fatty acids provide fluidity that is necessary for membrane fusion events (e.g., the acrosome reaction and sperm-egg interaction) and for sperm motility. However, the unsaturated nature of these molecules predisposes them to free radical attack and ongoing lipid peroxidation throughout the sperm plasma membrane. Once this process has been initiated, accumulation of lipid peroxides occurs on the sperm surface (this results in loss of sperm motility) and oxidative damage to DNA can ensue.
13,14SEMINAL ANTIOXIDANT CAPACITY AND SPERM DYSFUNCTION Seminal plasma and spermatozoa themselves are well endowed with an array of protective antioxidants to protect spermatozoa from OS, especially, at the post-testicular level. 6,15,16 Seminal plasma contains a number of high-molecular weigh...