THE EFFECTS OF RECOMBINANT FOLLICLE-STIMULATING-HORMONE ON THE RESTORATION OF SPERMATOGENESIS IN THE GONADOTROPIN-RELEASING HORMONE-IMMUNIZED ADULT-RAT

The role of FSH in spermatogenesis is unclear as testosterone alone ha s been reported to be sufficient in the gonadotropin-deficient rat. Th is study examined the effects of recombinant FSH on the restoration of spermatogenesis after gonadotropin withdrawal by GnRH immunization. A dult Sprague-Dawley rats received GnRH immunogen (100 mu g, sc, every 4 weeks) to induce gonadotropin deficiency, with severe spermatogenic regression occurring by 12 weeks. Recombinant human FSH was then given (10 or 50 IU/kg, sc, daily) for 7, 14, and 21 days, with data from bo th dosages combined in the analyses. Testes were perfusion fixed, and germ cell numbers were quantified by the optical disector technique. A fter 7 days of FSH, testis weight significantly increased by 43% (P < 0.01), with no further increases at 14 and 21 days. GnRH immunization severely reduced germ cell numbers, which were then significantly (P < 0.05) restored in all cell types, except elongated spermatids, by 7 d ays of FSH; type A spermatogonia (45% --> 61% of control), type B sper matogonia/preleptotene spermatocytes (46% --> 65%), leptotene/zygotene spermatocytes (39% --> 55%), pachytene spermatocytes in stages I-VIII (11% --> 30% control) and IX-XIV (4.3% --> 22% control), and round sp ermatids in stages I-VIII (1.4% --> 4.4% control). Prolonged FSH treat ment did not further increase type A spermatogonial or pachytene sperm atocyte number, whereas round spermatids increased to a peak of 12.8% of the control value. At no stage did FSH increase elongated spermatid numbers above 1% of the control level. The incorporation of bromodeox yuridine into spermatogonial and early spermatocyte nuclei did not cha nge after GnRH immunization or FSH treatment. Sertoli cell number was not altered by any treatment; however, Sertoli cell nuclear volume was significantly decreased from the control value by GnRH immunization ( 142 +/- 9 vs. 455 +/- 22 mu m(3); P < 0.01) and increased after 7 and 14 days of FSH treatment to 212 +/- 10 and 259 +/- 24 mu m(3), respect ively. FSH treatment restored serum inhibin levels to normal, but did not increase serum or testicular androgen levels. We conclude that rec ombinant FSH partially restores spermatogenesis in the gonadotropin-de ficient rat by increasing the number of spermatogonia and promoting su bsequent maturational steps up to the round spermatid stage. Spermatid elongation was not restored by FSH, indicating the need for an additi onal factor(s), most likely testosterone.