Gossypol was found to induce sterility in male rats when administered orally. A reduction in the number of spermatozoa in the epididymis from the gossypol-treated rats was observed when compared to the control animals. An examination of the spermatozoa from the treated rats showed the following ultrastructural modifications: disorganization of the mitochondiral sheath and missing cell membrane from the middle piece, broken cell membrane and missing members of both outer fibers and inner microtubules of the principal piece, and broken cell membrane of the sperm head. Serial mating experiments proved that gossypol-treated males were indeed sterile. The results suggest that gossypol at low concentrations is able to affect the motility of spermatozoa, thus contributing to its contraceptive action.
The effects of gossypol acetic acid (GAA) on various aspects of female rat reproduction were evaluated. Forty sexually mature, nulliparous female Holtzman rats received a daily, oral dose of GAA (20 mg GAA/Kg body wt) for 60 days. Nineteen control animals were utilized. Throughout the treatment period, GAA treated rats had significantly more irregular estrous cycles than did controls, and the mean duration of an estrous cycle in the GAA rats was significantly longer than that of controls. A significantly lower body weight gain was observed in all GAA treated animals. A prolonged time for mating, a decrease in incidence of pregnancy, and a reduction in number of viable embryos at Day 13 of gestation were noted among GAA treated animals. Weaning weights of offspring from GAA dams were significantly less than weaning weights of offspring from control dams.
Spermatozoa from the cauda epididymidis of gossypol-treated rats exhibit distinctive departures from the morphology of spermatozoa from control rats: wrinkled and disorganized cell membrane in the head and tail regions, cell membrane missing from segments of the tail midpiece and principal piece regions, malformed heads, decapitate spermatozoa, retention of a cytoplasmic droplet at variable loci along tail midpieces, and looped tails. The observations suggest that gossypol exerts its contraceptive effect during spermatocytogenesis and spermiogenesis, including the posttesticular development and maturation of spermatozoa in the epididymis.
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