Sperm, Reactive Oxygen Species (ROS) and Anti-Oxidants
Reactive oxygen species (ROS) are molecules that are highly disruptive to cellular function, in general, and have been shown to play a role in male factor infertility. ROS have free radicals, which are unpaired electrons which tend to bind other molecules and alter them. The ROS of primary interest are the superoxide anion (·O2` ), hydroxyl radical (·OH), and hypochlorite radical (·OHC1). These damage cells of all types and may play a role in as much as 40% of male factor infertility (1). The sperm cell is highly susceptible to damage by these highly reactive molecules because of its unique structure. The spermatozoon has a unique lipid membrane covering its head that is involved with attachment to the egg zona pellucida as well as important changes that occur with the capacitation reaction. The sperm head also contains important acrosome enzymes as well as the chromosomes that will eventually fuse with the maternal chromosomes. The mid-piece of the sperm generates the power to propel the tail by generating energy using its mitochondria. These mitochondria generate reactive oxygen molecules and are the aerobic source of cell energy. Semen also contains white blood cells, a very important source of ROS. The discussion below will review what ROS are and how they are generated. Studies will be reviewed that show an association with male factor infertility will be discussed as well as how the ROS affect the sperm components. Finally, studies using anti-oxidants will be reviewed as they relate to male factor infertility.
Sperm are produced in the testes and spend approximately 10 days in the epididymis where they undergo important maturation stages. It is in the epididymis that oxidative damage may occur to the sperm (2). Sperm have polyunsaturated fatty acids, making up approximately 40 % of the lipids in the sperm head, which are important for membrane fluidity, sperm motility, capacitation, and sperm binding to the egg zona pellucida. These polyunsaturated fatty acids are extremely susceptible to oxidative damage. ‘Oxidative Stress’ is an imbalance between the ROS generating factors and ROS scavenging systems. It is somewhat ironic that sperm may produce ROS when they utilize their oxidative metabolism to provide movement and so may damage them selves in addition to playing a role in normal sperm function such as hyperactivation, capacitation, acrosome reaction, oocyte penetration, and signal transduction (via tyrosine phoshorylase). The internal sources of sperm ROS are the mitochondria (primary) which generate hydrogen peroxide (H2O2) and the sperm plasma membrane NADPH oxidase system (3). External sources of ROS include white blood cells in the semen. These produce H2O2 and Oxygen (O2). The phagocytes and -lymphocytes produce –O2 which appear to use NADPH oxidase like enzymes. Low levels of ROS may be generated by other cells in the male reproductive tract including endothelial cells, fibroblasts, mesangial cells, and vascular smooth muscle cells (2). As you can see, overproduction could come from several sources. Infection of the prostate, i.e. prostatitis, is associated with decreased sperm motility, anti-sperm antibodies, and oxidative stress. ROS may be increased with certain medications, radiation, pollutants and in patients with spinal cord injuries (4).
The sperm scavengers in seminal plasma include vitamin E (a-tocopherol), vitamin C (ascorbic acid), uric acid, glutathione, taurine, hypotaurine, and albumin (see ref. 1). A group of enzymes (4) also help to scavenge oxygen radicals throughout the male reproductive tract (glutathione peroxidase, catalase, indolamine dioxygenase, and superoxide dismutase). It is important to realize that the body has redundant systems to remove these potentially toxic compounds. When these systems fail, it is possible that oxidative stress may occur leading to sperm damage. Experiments where sperm were exposed to artificially produced ROS showed DNA damage and programmed cell death (3).
Several investigations have looked at the effects of antioxidant
therapy. Sonmez et al
From the above it is clear that oxygen radicals may play a role in male factor infertility. Given the potential positive effects of supplementation, it may be reasonable to include this in our treatment of male patients.
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