Protection by Gonadal Steroid Hormones Against Procarbazine‐Induced Damage to Spermatogenic Function in LBNF1 Hybrid Rats

Abstract

ABSTRACT: Some anti‐cancer drugs, such as procarbazine (PCZ), are associated with irreversible damage to spermatogenic function and cause sterility in men. In the present study, protection of spermatogenesis by gonadal steroid hormones during PCZ treatment was investigated in male rats. LBNF1 hybrid rats were chosen for these studies because the response of the testis to PCZ was more uniform than in a stock of Sprague‐Dawley outbred rats. Mature male LBNF1 rats were subcutaneously implanted with cholesterol (C)‐, testosterone (T)‐, and/or estradiol‐17β (E)‐ containing capsules, and 5–10 weeks later given one or four weekly intraperitoneal injections of PCZ at a dose of 200–250 mg/kg of body weight. Hormone capsules were removed 24 hours after the last PCZ injection and the animals were killed 10–12 weeks later. Testicular weights, sonication‐resistant sperm head counts, and quantitative testicular histology revealed protection of the spermatogenic epithelium from PCZ toxicity by gonadal steroid hormones when compared with the C controls. Protection was observed against both single and multiple injections of PCZ. A combination of T and E capsules provided better protection than T alone. This model system is suitable for studies of the mechanism of protection of spermatogenesis from chemotherapy‐induced damage.