P-69: Cellular and Molecular Mechanism of Male Infertility in The Athletes That Abuse Anabolic Androgenic Steroids: Apoptosis in Spermatogenic Cells, Caspase 3 Activity and The Generation of Reactive Oxygen Species (ROS) in The Rat Model

Background: Anabolic-androgenic steroids are used at high doses by athletes for improving athletic ability, physical appearance and muscle mass. Unfortunately, the abuse of these agents has significantly increased. It has been established that exercise and high doses of anabolic-androgenic steroids may influence the hypothalamic- pituitary-testis axis, which can in turn affect testicular apoptosis. However, the effects of the combination of exercise and high dose of anabolic-androgenic steroids on testicular apoptosis and the generation of ROS are not known. Materials and Methods: Five groups of male Wistar rats were treated as follows for 8 weeks: solvent of nandrolone decanoate (peanut oil) as a vehicle (Sham); nandrolone decanoate (10 mg/kg/weekly) (ND); running exercise by treadmill (1 hour/day, 5 days a week) (EX); combination of nandrolone decanoate and running exercise (ND-EX) and sedentary control without any injection or exercise (CO). Apoptosis in germ cells was characterized by TUNEL, caspase-3 assay and the expression of Fas, FasL, Bax and Bcl2 by RT-PCR. Results: Testis weight significantly decreased in ND-EX but sperm count reduced in ND and ND-EX and sperm motility decreased in all experimental groups relative to the sham and control groups (p≤0.05). Germ cell apoptosis and Caspase 3 activity was increased in all experimental groups but it was so much in the ND and ND-EX groups. The expression of FAS and FasL was not significant but the expression of Bax was increased and Bcl2 was decreased in the all experimental groups. It shows that germ cell apoptosis in this experiment is from mitochondrial pathway. The generation of ROS was elevated in all experimental groups especially in the ND group (p≤0.05).Total Antioxidant was decreased in all experimental groups in comparison with CO and Sham groups. Conclusion: We concluded that running exercise seems to increase the extent of apoptotic changes caused by supraphysiological dose of nandrolone decanoate in rats, which in turn affects fertility.