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Arch Hellen Med, 22(5), September-October 2005, 433-446


Sperm oxidative damage and the role of reactive oxygen species in male infertility

Laboratory of Histology and Embryology, Medical School, University of Athens, Athens, Greece

Infertility may be due, to a very large extent, to the male factor. Reactive oxygen species (ROS) found in sperm of poor quality are produced by either the spermatozoa or the leucocytes. Mitochondria are the basic source of ROS and are involved in the activation of proapoptotic molecules, DNA fragmentation and apoptosis. Excessive generation of ROS in the ejaculate affects the functional competence of human spermatozoa and has been associated with decreased motility, loss of the capacity to undergo the acrosome reaction, decreased spermoocyte fusion capability and diminished fertility in vitro and in vivo. The mechanism by which ROS disrupt sperm function involves the peroxidation of unsaturated fatty acids in the sperm membranes and DNA fragmentation. Oxidative damage of the mitochondrial DNA leads to reduced production of ATP, affecting reproductive capacity, while nuclear DNA damage is detrimental to the structure and function of the sperm. Techniques such as TUNEL and comet, which are efficient in detecting DNA breakage in ejaculated spermatozoa from subfertile men, showed that a high incidence of fragmented DNA correlated with adverse effects on sperm motility, morphology, sperm count and the percentage of fertilization after intracytoplasmic sperm injection (ICSI). The results reported to date of in vivo antioxidant treatment are modest. Antioxidants could be useful in the case of excessive levels of ROS found during sperm selection for in vitro fertilization (IVF) or intrauterine injection (IUI), but further studies are needed to ascertain their role in the treatment of male infertility. Analysis, using new techniques, of the action of antioxidants and subsequent design/synthesis of new compounds with optimal antioxidant action are necessary for the improvement of sperm quality and the treatment of male infertility.

Key words: DNA fragmentation, Male infertility, ROS, Spermatozoa.

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