TRIPTOLIDE - A POTENTIAL MALE CONTRACEPTIVE

The antifertility effect of triptolide and other related compounds, is olated from Tripterygium wilfordii, has been demonstrated in male rats . The exact sites and mechanism of action of triptolide remain unknown . Our objectives were to determine whether triptolide at selected dose levels that induce infertility has any detrimental effects on the tes tes and to determine the sites and the possible mechanisms of its acti on. Groups of six adult male Sprague-Dawley rats were given oral admin istration of either vehicle (control group) or triptolide (50 or 100 m u g/kg body weight) daily for 35 or 70 days. Body weight gain was norm al in all treated groups. All six rats treated with a high dosage of t riptolide were infertile during the second (63-70 days) mating trial. A lower dose (50 mu g) of triptolide gave intermediate fertility value s. Plasma levels of luteinizing hormone, follicle-stimulating hormone, testosterone, and intratesticular testosterone were not significantly different between control and triptolide-treated groups. Cauda epidid ymal sperm content was decreased by 68% and the motility, which averag ed 58.2% in the control rat, was reduced to almost zero. No effects of triptolide were observed on testis and accessory organs weight, volum es of tubular lumen and the total Leydig cells, tubule diameter, and t he number of Sertoli cells, spermatogonia, preleptotene (PL), and pach ytene (P) spermatocytes. There were, however, modest but significant d ecreases in tubule volume and the number of round spermatids at stages VII-VIII. No changes in the germ cell apoptotic index measured at sta ges VII-VIII and XIV-I were noted between controls and rats rendered i nfertile with a high dose or triptolide. Thus, triptolide, at a dose l evel that induces complete infertility in the adult rats, has minimal adverse effects on the testes and acts primarily on the epididymal spe rm making triptolide an attractive lead as a post-testicular male cont raceptive.