Role of melatonin in mitigating chemotherapy-induced testicular dysfunction in Wistar rats

Testicular cancer is the most common cancer affecting men of reproductive age, and its incidence is increasing steadily. A regimen of cisplatin (P), vinblastin (V) and bleomycin (B) (PVB) is the standard chemotherapy for testicular cancer. Though PVB-based chemotherapy has been widely used against germ cell tumors, it is associated with induction of oxidative toxicity and a transient or permanent loss of fertility. However, the mechanism of action of PVB on the testis is not thoroughly elucidated. Using a rat model, we investigated the persistence of the effects of PVB on steroidogenesis, spermatogenesis and testicular oxidative status and architecture. Further, we have also studied whether administration of melatonin has any protective effect on testicular physiology in the PVB-treated rats, since melatonin exerts influence on the antioxidant defense system. The body weight of the PVB-treated rats did not show significant change as compared with the control group. Significant decrease in the weight of the testis was observed with a reduction in volume in the PVB-treated rats. Administration of PVB caused a reduction in the testicular steroidogenesis and spermatogenesis. The circulatory levels of testosterone were also significantly reduced with an elevation of FSH and LH in the PVB-treated rats. Testicular architecture was severely affected with a reduction in seminiferous tubule diameter and epithelial height. The activities of superoxide dismutase and catalase were decreased while the levels of lipid peroxidation increased significantly in the testis of the PVB-treated rats indicating depletion of antioxidant defence system and elevation of oxidative stress. Co-administration of melatonin mitigated these changes in the PVB-treated rats.