Gossypol: its toxicological and endocrinological effects in male rabbits

The effects of different doses of orally administered polyphenolic compound 'Gossypol' on semen quality, circulating testosterone (T) and fertility of Dutch-belted male rabbits were studied. Bucks fed daily with 80, 40, 20 mg/kg day gossypol died within 8-17, 23-35 or 35-84 days, respectively, after initiation of treatment. Following gossypol treatment at 80, 40 or 20 mg/kg/day, animals lost appetite and body weight, developed hind limb paralysis, breathing difficulties and collapsed while sitting in their cages. At autopsy, the liver and lungs were found congested while the stomach and intestines contained gases. On the other hand, rabbits fed daily with 10 mg/kg/day gossypol exhibited a survival time ranging from 77 to 250 days. Despite the severe side effects resulting in eventual deaths, weekly semen samples from all treated animals did not show any apparent change in sperm motility, morphology or population. Likewise, gossypol-treated males mated to estrous does exhibited a fertility comparable to vehicle-treated controls. Gossypol fed at a dose of 10 mg/kg/day for up to 35 weeks failed to induce sterility. Male rabbits, fed with either 20 or 10 mg/kg/day gossypol, that survived for longer periods of time had substantially reduced T levels by 12-20 weeks depending upon the dose but were fertile at all times. When the in vitro release of T from the rat testes mince in the presence of hCG and gossypol was evaluated, an inhibiton of T release was recorded. It is concluded that although gossypol has been shown to be an effective antifertility agent in several mammalian species, it failed to exhibit such an effect in Dutch-belted rabbits, although serum T levels were reduced. In addition, gossypol exhibited a wide spectrum of toxicity. The in vitro study demonstrated that high concentration of gossypol can directly inhibit the T synthesis in the testis.