Effects of gossypol on reproductive and endocrine functions of male cynomolgus monkeys (Macaca fascicularis).

Abstract

Adult male cynomolgus monkeys were treated orally with 5 (n=4) or 10 (n=3) mg per kg per day of gossypol acetic acid (gossypol) for 6 months. A significant decrease in sperm concentration and motility,determined by evaluating semen ejaculates,was observed without any significant decrease in circulatinglevelsof testosterone (T) among 10 mg per kg per day gossypol-treated animals. Similarly, there was no significant difference in plasma T levels after an intravenous bolus injection of luteinizing hormone releasing hormone (LHRI-l) (50 �sg/animal) between control and gossypol-treated animals, further suggesting an adequate release of pituitary luteinizing hormone (LH) and normal Leydig cell function. Transient azoospermia was observed in 1 out of 4 and in 2 out of 3 animals after 4 months of gossypol treatment at 5 and 10 mg per kg per day, respectively. The effects of gossypol (10 mg per kg per day) were more dramatic and consistent on sperm motility. No striking abnormality of spermatozoa was observed by light microscopy, although there was an increase in the number of sperm with coiled or broken tail pieces and an occasional detached head and tail. However, at the ultrastructural level disruption of the axial complex was commonly observed with gossypol treatment. The effect was manifested at 5 mg per kg per day as a disruption of radial arms. At 10 mg per kg per day the entire axial complex was frequently destroyed, suggesting an impairment of sperm motility. No serious clinicopathologic side effects were observed except temporary diarrhea and anorexia among 10 mg per kg per day gossypoltreated animals during the initial stages of treatment. In addition, gossypol had a hypolipidemic effect which is a new significant entity for this compound. In conclusion, it is suggested that gossypol may be interfering with spermatogenesis and/or directly acting on the sperm itself within the testis or during its passage through the male reproductive tract in ways thataffectboth sperm production and sperm motility.