[Frontiers in Bioscience 1, e78-86, August 1,1996]
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CAVEAT LECTOR



OXIDATIVE STRESS AND ROLE OF ANTIOXIDANTS IN NORMAL AND ABNORMAL SPERM FUNCTION

Suresh C. Sikka, Ph.D., HCLD

Department of Urology, Tulane University School of Medicine, New Orleans, Louisiana, USA

Received 05/30/96; Accepted 07/02/96; On-line 08/01/96

6. ANTIOXIDANTS (POTENTIAL SCAVENGERS OF ROS) AND OXIDATIVE STRESS

Antioxidants, in general, are compounds and reactions which dispose, scavenge, and suppress the formation of ROS, or oppose their actions. A variety of biological and chemical antioxidants that attack ROS and LPO are presently under investigation. Among the well known biological antioxidants, SOD and its two isozymes, and catalase have a significant role. SOD spontaneously dismutates (O2-). anion to form O2 and H2O2, while catalase converts H2O2 to O2 and H20.

SOD
2 (O2-). + 2H+-------------------------------------->H2O2 + O2
Catalase
H2O2-------------------------------------->H2O + ½ O2

Many studies have been reported in the literature on the role of SOD as an antioxidant in reproductive biology. SOD protects spermatozoa against spontaneous O2 toxicity and LPO [18]. SOD and catalase also remove (O2-). generated by NADPH-oxidase in neutrophils and may play an important role in decreasing LPO and protecting spermatozoa during genitourinary inflammation (30).

Glutathione peroxidase, a selenium-containing antioxidant enzyme with glutathione as the electron donor removes peroxyl (ROO.) radicals from various peroxides including H2O2 (31). Glutathione reductase then regenerates reduced GSH from GSSG as shown in the following equation:

peroxidase-(Se)
2GSH + H2O2----------------------------------->GSSG + 2H2O
reductase
GSSG + NADPH + H+----------------------------------->2GSH + NADP+

A selenium-associated polypeptide, presumably glutathione peroxidase, has been demonstrated in rat sperm mitochondria which plays a significant role in this peroxyl scavenging mechanism and in maintaining sperm motility (31). It would be interesting to explore the mechanism of action of this antioxidant in human spermatozoa. In addition, GSH-peroxidase and GSH-reductase may directly act as antioxidant enzymes involved in the inhibition of sperm LPO (28). GSH has a likely role in sperm nucleus decondensation and may alter spindle microtubule formation in the ovum, thus affecting the outcome of pregnancy. In this context, the gamma-glutamyl transpeptidase (GGT), considered to be present in the midpiece and acrosomal regions of spermatozoa of certain mammalian species (e.g., the boar) may further affect GSH content of oocyte at the time of sperm penetration (19, 28). Thus, in view of the great number of mitochondria in spermatozoa, these antioxidant mechanisms are important in the maintenance of sperm motility, the rate of hyperactivation, and the ability of sperm to undergo acrosome reaction during sperm preparation techniques especially in the absence of seminal plasma. Albumin, used in sperm-washing procedures, is likely to serve as an antioxidant by providing thiol groups required for "chain breaking" antioxidant activity (26). A high GSH/GSSG ratio will help spermatozoa to combat oxidative insult (5). It seems that the role of these GSH enzymes and their associated mechanisms as related to biological antioxidants in infertility is an important area for further investigation.

Within the category of chemical antioxidants, both natural and synthetic products have garnered attention by the cosmetic, nutritional, and pharmaceutical industries. Their usefulness in reproduction and management of infertility has not yet been demonstrated. Although vitamins E and C may protect spermatozoa against endogenous oxidative DNA and membrane damage they have minimal effects in improving the post-thaw sperm parameters. In this regard, carotenoids (beta-carotene), and ubiquinols may also play a role in quenching singlet oxygen and reducing lipid derived free-radicals with detrimental effects on sperm LPO (26).

Hence, the application of ROS scavengers (e.g., SOD, catalase, vitamin E, GSH-enzymes) is likely to improve sperm motility and function. Pentoxifylline, a sperm motility stimulator, can also act as a suppressor or scavenger of ROS (32). The effect of vitamin E supplementation in combination with IVF techniques is a worthy notion. Further controlled clinical studies will determine if many of these putative antioxidants can improve infertility in selected groups of patients.

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