TIME-COURSE OF RECOVERY OF SPERMATOGENESIS AND LEYDIG-CELL FUNCTION AFTER CESSATION OF GONADOTROPIN-RELEASING-HORMONE ANTAGONIST TREATMENT IN THE ADULT-RAT

This study examined the time course of recovery of spermatogenesis and its relationship to the temporal changes in circulating levels of gon adotropin and testosterone (T) and intratesticular T levels after cess ation of treatment with a potent GnRH antagonist (GnRH-A). Adult male rats were given a daily sc injection of Nal-Glu-GnRH antagonist (1250 mug/kg BW) for 4 weeks and killed in groups of five 0, 1, 2, 3, 4, and 6 weeks after discontinuation of treatment. After cessation of treatm ent, plasma FSH levels returned to control values by 6 weeks, whereas LH levels returned to control values within 1 week. Both circulating a s well as intratesticular levels of T returned to normal levels by 3 a nd 4 weeks, respectively. Interestingly, a rebound in both FSH and int ratesticular T, but not in plasma T, beyond control levels occurred ea rly in the recovery phase. The total volume of Leydig cells, which was only 15% of control values, increased 4.3-fold within 1 week and was not significantly different from control values (92% recovery) by 2 we eks posttreatment. Enumeration of earlier phases of germ cells as well as homogenization-resistant advanced (steps 17-19) spermatids reveale d a progressive increase in germ cell numbers with time. Complete rest oration of the numbers of preleptotene spermatocytes, pachytene sperma tocytes, step 7 spermatids, and advanced spermatids occurred 1, 3, 4, and 6 weeks, respectively, after termination of GnRH-A treatment. Ther e was also a complete reversal of GnRH-A-induced changes in testicular weight, tubule diameter, and volume of seminiferous tubules and their lumens by 6 weeks posttreatment, paralleling the recovery of spermato genesis. These results suggest that 1) complete recovery of spermatoge nesis and various other testicular parameters can be achieved in GnRH- A-treated rats after cessation of treatment; 2) the progression of var ious germ cells during the recovery period follows the normal time sch edule of germ cell development; and 3) the recovery of spermatogenesis is preceded by supranormal levels of FSH and intratesticular T. These findings further emphasize the suitability of antagonistic analogs of GnRH for male fertility control.