Human Follicle-Stimulating Hormone Exerts a Stimulatory Effect on Spermatogenesis, Testicular Size, and Serum Inhibin Levels in the Gonadotropin-Releasing Hormone Antagonist-Treated Nonhuman Primate (Macaca fascicularis)*

The role of FSH in spermatogenesis was investigated in nonhuman primates depleted of testosterone by GnRH antagonist treatment. The GnRH antagonist antide (Nal-Lys; [N-acetyI-D-2-naphthyl-Ala1,D-4-ch]oro-Phe2,D-pyrLdyl-Ala3, nicotinyl-Lys5,D-nicotinyl-Lys5,isopropyl-Lys8,D-Ala10]-GnRH) was used at a daily dose of 450 μg/kg to suppress endogenous gonadotropin and androgen production. Four groups of five cynomolgus monkeys (Macaca fascicularis) were subjected to the following treatment throughout a 16-week period: vehicle (group 1), GnRH antagonist (group 2), and GnRH antagonist plus human FSH (Fertinorm; 2 × 15 IU/day-animal; hFSH) during weeks 0-8 (group 3) or 8-16 (group 4). Testicular biopsies were performed before and after 4, 8, and 16 weeks of treatment. The tissue was analyzed by light microscopy and flow cytometry. Serum testosterone levels were suppressed into the range of ore hidec torn ized animals in all GnRH antagonist-treated groups. In the absence of hFSH, serum inhibin levels were also markedly lowered. Concomitant administration of hFSH attenuated the GnRH antagonist-induced reduction of testicular size, while delayed treatment with hFSH failed to restimulate testicular volume. Numbers of A-dark spermatogonia, the reserve stem cells, were not altered by any of the treatments. hFSH either fully maintained or increased the counts for A-pale spermatogonia (renewing stem cells). The development of pachytene spermatocytes and round and elongated spermatids was markedly reduced or inhibited by the GnRH antagonist within 6-18 weeks. In contrast, hFSH maintained these cell types at about 50% of baseline for 8 weeks. After 8 weeks of GnRH antagonist administration, hFSH stimulated A-pale spermatogonia and spermatocytes 2-to 3-fold with only minor effects on spermatid numbers. By means of flow cytometry, testicular cells were quantified according to DNA content. Within 8-16 weeks of GnRH antagonist treatment the percentage of 4C (mainly primary spermatocytes), lC (round spermatids), and ICC cells (elongated spermatids) had fallen from 65-75% to 5-25%. hFSH completely maintained the relative number of these cells, but failed to significantly restimulate the formation of ICC cells. From the present work in the GnRH antagonist-suppressed nonhuman primate model the following conclusions are drawn: 1) FSH exerts a stimulatory effect on testicular size and spermatogenesis; 2) the effects of FSH might be mediated via activation of the renewing testicular stem cells; 3) the ability of FSH alone to restart spermatogenesis is limited; and 4) simultaneous analysis of testicular biopsy material by light microscopy and flow cytometry provides a valuable approach for qualitative and quantitative assessment of spermatogenesis in the nonhuman primate. (Endocrinology129: 1831–1839,1991)