TEMPORAL AND STAGE-SPECIFIC CHANGES IN SPERMATOGENESIS OF RAT AFTER GONADOTROPIN DEPRIVATION BY A POTENT GONADOTROPIN-RELEASING-HORMONE ANTAGONIST TREATMENT

GnRH antagonists (GnRH-As) rapidly and reversibly inhibit testicular f unctions in a variety of experimental models as well as man. Their pot ential for human male contraception is currently being tested in many centers, including our own. This study was undertaken to provide compr ehensive quantitative information on the testes and to document the te mporal and stage-specific changes in the kinetics of germ cell degener ation in rats treated daily with the Nal-Glu GnRH-A (1250 mug/kg body wt) for up to 4 weeks. Plasma levels of testosterone (T) and the conce ntrations of testicular T declined to 20.7% and 5.4% of control values , respectively, by 1 week and remained suppressed throughout the treat ment period. Preleptotene and pachytene spermatocytes, and step-7 and step-19 spermatids at stage VII were the first germ cells to degenerat e soon after (1 week) GnRH-A treatment. Germ cell counts at stage VII also revealed a significant (P < 0.05) reduction in number of prelepto tene (25.6%), pachytene (35.4%), and step-7 spermatids (29.1%) in comp arison with controls. The number of homogenization-resistant advanced spermatids decreased by 70%. A further progressive loss of spermatogen ic activity occurred with time. Treatment with GnRH-A for 4 weeks caus ed advanced spermatids to decline to nearly undetectable, Step-7 sperm atids to decline to 17.7% of the normal level, and the P and PL to dec line to 28.6% and 67.7%, respectively, of control values. The number o f Sertoli cells and A, spermatogonia remained unchanged throughout the experimental period. The effects of GnRH-A treatment on spermatogenes is were identical to that of hypophysectomy. These results suggest tha t: 1) early deprivation of gonadotropins and/or intratesticular T by G nRH-A treatment is followed by stage-specific degeneration of germ cel ls; 2) pituitary secretions other than LH and FSH have little primary influence on spermatogenesis during early regression; and 3) the GnRH- A-treated rat would be an excellent animal model for studying the targ eted effects of LH, FSH, and T on the regulation of spermatogenesis.