ACUTE AND SPECIFIC IMPAIRMENT OF SPERMATOGONIAL DEVELOPMENT BY GNRH ANTAGONIST-INDUCED GONADOTROPIN WITHDRAWAL IN THE ADULT MACAQUE (MACACA-FASCICULARIS)

This study examined the effect of GnRH-antagonist (GnRH-A)-induced gon adotrophin withdrawal on numbers of germ cells in adult cynomolgus mon keys and aimed to identify the site of the earliest spermatogenic lesi on(s) produced. Animals received either GnRH-A (Cetrorelix; 450 mu g k g(- 1) day(- 1) s.c.; n = 5) or vehicle (control, n = 4) for 25 days. One testis was removed on day 16 and the other testis on day 25. The o ptical disector stereological method was used to estimate germ and Ser toli cell numbers per testis. After GnRH-A treatment for 16 days, the number of type A spermatogonia was unchanged; however, type B spermato gonia (15% of control), preleptotene + leptotene + zygotene (15% contr ol) and pachytene (55% control) spermatocytes were all reduced (P < 0. 05). By day 25, these cells were further reduced together with step 1- 6 spermatids (38% control; P < 0.05). More mature germ cells were unaf fected. The proportion of type A pale spermatogonia at stages VII-XII was reduced (P < 0.05) in GnRH-A-treated groups (52% on day 16, 43% on day 25) compared with control (67%). After 25 days of GnRH-A treatmen t, the number of: Sertoli cells was unaltered but nuclear volume was r educed (66% control, P < 0.05). Tubule length was unchanged but volume (50% control), diameter (62% control) and epithelial thickness (59% c ontrol) were reduced (P < 0.05). GnRH-A treatment suppressed serum tes tosterone concentrations into the castrate range, and testicular testo sterone concentrations to 21-36% of control values. Serum inhibin (as an index of FSH action) was suppressed in GnRH-A-treated animals by da y 16, declining to 38% of control concentrations at day 25. Therefore, the primary lesion produced by GnRH-A induced gonadotrophin withdrawa l is the rapid and profound reduction in the number of type B spermato gonia. The time course of germ cell loss suggests the inhibition of ty pe A pale spermatogonial mitosis as the primary mechanism. Later germ cell maturation, specifically meiosis and spermiogenesis, appears to p roceed unaffected. The decline in late spermatocytes and spermatids by 25 days of GnRH-A treatment is attributed to a 'depletional wave' fro m the spermatogonial lesion. The fact that such marked spermatogenic d isruption occurs in the face of substantial testicular testosterone co ncentrations implies a significant role for FSH in spermatogonial deve lopment.