|[Frontiers in Bioscience 1, e78-86, August 1,1996]|
OXIDATIVE STRESS AND ROLE OF ANTIOXIDANTS IN NORMAL AND ABNORMAL
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
Some forms of infertility are caused by age-related degenerative disorders of the testis. As apparent from the declining sperm population over the last two generations, this problem is increasing in industrialized societies (36). Although the decline in sperm numbers is considered to be associated with male fetal and/or neonatal exposure to increased level of the environmental estrogen , the idiopathic male infertility may also be explained as a form of premature or differential aging of the testis induced by ischemia and oxidative stress associated with defective mitochondrial genome that controls the oxidative phosphorylation (29). Presence of retained cytoplasmic droplets on spermatozoa due to imperfect spermiation in aging testis may be a sign of' reduced fertility. It is known that lipid peroxidation (LPO) and midpiece anomalies are linked (37), and that the increased rate of LPO and creatine kinase (CK) activity in immature sperm is due to incomplete cytoplasmic extrusion during terminal spermatogenesis (38). In addition, Sertoli cells abnormality in infertile men may well be central to the development of spermatogenic failure due to faulty spermiation and maybe related to genetic defects, oxidative stress, or even aging of the gonads.
Decreased vascularity, increased spermatogenic failure, and reduced sperm output occur with senescence in a variety of animal species and in humans (39). Degenerated germ cells are presumably phagocytosed by Sertoli cells, resulting in lipid accumulations that increase progressively with age. Increased levels of lipofuscin and lipid are seen intracellularly, suggesting presence of mitochondrial dysfunction possibly compounded by oxidative stress in the older population (40). These degenerative changes in gonads associated with accumulation of lipofuscin pigment and multiple nuclei are considered to be due to ROS-induced lipid peroxidation with age (40). Most of these changes are strikingly similar to that seen in men with idiopathic testicular failure, probably due to induced gonadotoxicity. However, functional abnormalities in mature spermatozoa leading to infertility has not been demonstrated in normal aging men.