Upregulation of AP1 by tertiary butyl hydroperoxide induced oxidative stress and subsequent effect on spermatogenesis...

Oxidative stress is detrimental to sperm function and a significant factor in the etiology of male infertility. Present study evaluates the effect of ter butyl hydroperoxide (TBHP)-induced oxidative stress on the spermatogenic process and cell number in the seminiferous tubules. Intraperitoneal injection of TBHP (84 mumol TBHP/100 g body weight) for 2 weeks to male Balb/c mice resulted in enhanced lipid peroxidation (P < 0.0001) decrease in reduced glutathione (P < 0.0001) and increase in the oxidized glutathione levels (P = 0.007) in the testis. Status of spermatogenesis after the treatment was assessed by the quantitative methods of germ cell evaluation in the seminiferous tubules. A significant decrease in the number of young spermatids (P = 0.0003) and pachytene cells (P = 0.022) was observed. A marked reduction was also seen in the mature spermatid number (P < 0.0001). An increase in testicular mRNA levels of redox-regulated cjun (P = 0.008) and cfos (P = 0.0006) subunits of activator protein 1 (AP1) was observed after TBHP treatment. Evaluation of AP1 regulated antioxidant enzymes in the testis revealed an increase in gamma-glutamyl cysteine synthetase (GCS) mRNA expression (P = 0.001). These results suggest a potential role of AP1 in oxidative stress-mediated meiotic and post meiotic changes in the spermatogenic process and regulation of cell number in male reproductive system.