McLachlan R I, Wreford N G, de Kretser D M, Robertson D M
Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia.
Endocrinology. 1995 Sep;136(9):4035-43. doi: 10.1210/endo.136.9.7649112.
The role of FSH in spermatogenesis is unclear as testosterone alone has been reported to be sufficient in the gonadotropin-deficient rat. This study examined the effects of recombinant FSH on the restoration of spermatogenesis after gonadotropin withdrawal by GnRH immunization. Adult Sprague-Dawley rats received GnRH immunogen (100 micrograms, 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 both dosages combined in the analyses. Testes were perfusion fixed, and germ cell numbers were quantified by the optical disector technique. After 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 days of FSH; type A spermatogonia (45%-->61% of control), type B spermatogonia/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 spermatids in stages I-VIII (1.4%-->4.4% control). Prolonged FSH treatment did not further increase type A spermatogonial or pachytene spermatocyte 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 bromode-oxyuridine into spermatogonial and early spermatocyte nuclei did not change 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 microns 3; P < 0.01) and increased after 7 and 14 days of FSH treatment to 212 +/- 10 and 259 +/- 24 microns 3, respectively. FSH treatment restored serum inhibin levels to normal, but did not increase serum or testicular androgen levels. We conclude that recombinant FSH partially restores spermatogenesis in the gonadotropin-deficient rat by increasing the number of spermatogonia and promoting subsequent maturational steps up to the round spermatid stage. Spermatid elongation was not restored by FSH, indicating the need for an additional factor(s), most likely testosterone.
促卵泡激素（FSH）在精子发生过程中的作用尚不清楚，因为据报道，在促性腺激素缺乏的大鼠中，仅睾酮就足以维持精子发生。本研究通过GnRH免疫来诱导促性腺激素缺乏，进而研究重组FSH对促性腺激素撤除后精子发生恢复的影响。成年Sprague-Dawley大鼠每4周皮下注射100微克GnRH免疫原，以诱导促性腺激素缺乏，到12周时出现严重的生精功能衰退。随后给予重组人促卵泡激素（10或50 IU/kg，皮下注射，每日1次），持续7、14和21天，分析时将两种剂量的数据合并。对睾丸进行灌注固定，采用光学分割技术对生殖细胞数量进行定量分析。FSH治疗7天后，睾丸重量显著增加43%（P<0.01），14天和21天时未进一步增加。GnRH免疫严重减少了生殖细胞数量，而FSH治疗7天后，除延长型精子细胞外，所有细胞类型的生殖细胞数量均显著恢复（P<0.05）；A型精原细胞（从对照组的45%恢复至61%）、B型精原细胞/前细线期精母细胞（从46%恢复至65%）、细线期/偶线期精母细胞（从39%恢复至55%）、I-VIII期粗线期精母细胞（从对照组的11%恢复至30%）和IX-XIV期粗线期精母细胞（从4.3%恢复至22%），以及I-VIII期圆形精子细胞（从1.4%恢复至4.4%）。延长FSH治疗时间并未进一步增加A型精原细胞或粗线期精母细胞的数量，而圆形精子细胞增加至对照组值的12.8%的峰值。在任何阶段，FSH均未使延长型精子细胞数量增加至对照组水平的1%以上。GnRH免疫或FSH治疗后，溴脱氧尿苷掺入精原细胞和早期精母细胞核的情况未发生变化。任何处理均未改变支持细胞数量；然而，GnRH免疫使支持细胞核体积从对照组值显著降低（142±9 vs. 455±22立方微米；P<0.01），FSH治疗7天和14天后分别增加至212±10和259±24立方微米。FSH治疗使血清抑制素水平恢复正常，但未增加血清或睾丸雄激素水平。我们得出结论，重组FSH通过增加精原细胞数量并促进直至圆形精子细胞阶段的后续成熟步骤，部分恢复了促性腺激素缺乏大鼠的精子发生。FSH未能恢复精子细胞延长，这表明需要其他因素，最可能是睾酮。
