Inhibition of spermatogenesis, motility and metabolic enzymes of sperm by gossypol.

Abstract

Available data about gossypol a potential male antifertility agent explain its inhibition of spermatogenesis and possible mechanism of action. Spermatogenesis in rats has been inhibited by gossypol with no adverse effects on Leydig cells or Sertoli cells. The degree of damage to rat testes seminiferous epithelium was dose and duration related. Opinion varies regarding the site and mechanism of gossypols antifertility action. Early studies suggested an inhibition of the development of the spermatozoal nucleus and acrosome indicating a site of action for gossypol at the level of the testes but not the epididymis. Other studies did not confirm spermatozoal head defects but rather showed lesions in the spermatozoa tail in the epididymis. This discrepancy may indicate differences in spermatozoa response to gossypol with various mature stages. Other studies with rats and guinea pigs indicated an inhibitory action of gossypol preventing epididymal spermatozoa from attaining maturation. No consensus about the nature or site of gossypols antifertility action has been reached. In men the 1st effect of gossypol is a rapid loss of spermatozoa motility followed by a reduction of spermatozoa count. This decreased motility resulted from a reduction in energy supply through inhibition of glycolysis and the respiratory chain and the uncoupling of oxidative phosphorylation and reduction in ATP synthesis. The influence of gossypol on the tubulin-dynein system has recently been investigated in sea urchins. Gossypol has also been shown to inhibit the activity of several enzymes involved in energy metabolism including several dehydrogenases. Gossypol also decreased adenylate cyclase activity and inhibited fructolysis in human spermatozoa. Oral administration of gossypol at 12-30 mg/kg/day for 5-12 weeks induced infertility in rats hamsters guinea pigs dogs monkeys and men.