THE EFFECT OF COMBINED USE OF GOSSYPOL AND TRIPTERYGIUM WILFORDII ON THE FERTILITY OF MALE RATS

The total glycosides of Tripterygiura wilfordii Hook. f(GTW), a ready-n de Chinese herb medicine used for the treatment of rheumatoid arthritis and various skin diseases, have been found to cause a reversible infertility in male rats at a dose showing no toxic manifestations. It was recently shown in a retrospective study to be also antispermatogenic in men. The present study was designed to investigate the effect of combined use of sub-effective doses of gossypol and GTW to see if their effects could be additive.GTW and gossypol, suspended in 1% CMC, were given to adult male SD rats through gastric garage at a similar daily dose of 5 mg/kg, 6 times a week, for 11 weeks. Groups taking the vehicle and the same dose of GTW or gossypol alone were set as the controls. At the end of the 11th week, all the rats of the GTW-gossypol group became infertile as assessed by sequential fertility tests, while the mating behavior was present. The density and motility of spermatozoa in the cauda epididymis were dramatically decreased. No perceptible changes were seen in the Leydig cells, Sertoli ceils and in most eases in the seminiferous and epididymal epithelia under light microscope. All other parameters examined, including body weight growth, serum testosterone level and the histology of various organs, were not significantly different from the vehicle controls. Both the fertility and the epididymal spermatozoa were completely restored 6 weeks after cessation of treatment. In the remaining 3 groups, the fertility and epididymal spermatozoa were normal. The results indicate that the effects of GTW and gossypol on the fertility of male rats are additive and reversible, which may provide a potential approach to the alleviation of the side effects of both drugs.