The cycle duration of the seminiferous epithelium remains unaltered during GnRH antagonist-induced testicular involution in rats and monkeys

Abstract

Although the gonadotropic control of the spermatogenic process is well established, the endocrine regulation of the timing and kinetics of germ cell development has received little attention. We found previously that the administration of a GnRH antagonist (ANT) over a period of 25 days could retard spermatid development and slightly prolong cycle length in intact adult cynomolgus monkeys (Macaca fascicularis). The aim of the present study was to investigate the effects of extended exposure to ANT on the duration of the cycle of the seminiferous epithelium in the monkey. Additionally, the duration of spermatogenesis was studied in the ANT-exposed rat model. In experiment 1, monkeys were given either saline or ANT (n=6/group) and on day 30 all animals received a single injection of 5-bromodeoxyuridine (BrdU) to label S-phase germ cells. Testicular biopsies were taken on days 39, 43, 47 and 51 (end of treatment) for BrdU localization and flow cytometric analysis. ANT treatment suppressed hormone levels, reduced testis size by >70% and severely impaired germ cell production. Despite these alterations, cycle duration remained unchanged at all time-points compared with controls (10.12+/-0.15 days vs 10.16+/- 0.44 days). In experiment 2, adult male Sprague-Dawley rats (n=15/group) received either vehicle (VEH) or ANT for 14 days and received BrdU injection on day 2. Cycle duration was found to be shorter in the ANT-treated group (12.45+/-0.09 days) than in the control group (12.75+/-0.08, P<0.05). As spermatogenic cycle length in this control group was longer than that of our historical controls (range: 12.37-12.53 days), experiment 2 was repeated (n=10/group). In experiment 3, cycle duration was 12.51+/-0.02 for VEH and 12.46+/-0.05 for the ANT-treated group (P>0.05) in both species. We concluded that the duration of the cycle of the seminiferous epithelium in monkeys and rats is independent of gonadotropins but is rather regulated by the spermatogenic tissue itself.