Effects of Betulinic Acid on the Male Reproductive System of a Streptozotocin-Nicotinamide-Induced Diabetic Mouse Model

PURPOSE The present study was conducted to evaluate the favorable or harmful effects of betulinic acid (BA) on a diabetic reproductive system. MATERIALS AND METHODS In this experimental study, 60 male Naval Medical Research Institute mice (20∼25 g) were randomly divided into 6 groups: control, diabetes, diabetes+BA (10, 20, and 40 mg/kg), and diabetes+ metformin (200 mg/kg). A diabetic model was induced by a single dose of streptozotocin (STZ) (65 mg/kg) injection intraperitoneally 15 minutes after an intraperitoneal administration of nicotinamide (NA) (120 mg/kg). BA and metformin were gavaged for 2 weeks after confirmed diabetes induction in the treatment groups. One day after the last treatment, plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels were evaluated. The cauda epididymis and testis were removed to analyze the sperm count and testis histopathology. RESULTS LH levels increased in diabetic (p<0.001) and diabetic BA-treated mice (p=0.009). Plasma levels of testosterone (p< 0.001) and sperm count (p=0.04) decreased in these groups when compared to the control group. Furthermore, administration of 10 mg/kg (p=0.001), 20 mg/kg (p=0.004), or 40 mg/kg (p<0.001) of BA led to a greater reduction in plasma testosterone levels compared to the diabetes group. Seminiferous tubule vacuole numbers increased in diabetic and diabetic BA-treated mice, but testis morphology and FSH level assessment revealed no significant differences between the groups. CONCLUSIONS STZ-NA can induce diabetic alterations in the male reproductive system and the administration of BA in diabetic treated mice resulted in a worse outcome.