Effect of FSH on testicular morphology and spermatogenesis in gonadotrophin-deficient hypogonadal mice lacking androgen receptors

Abstract

FSH and androgen act to stimulate and maintain spermatogenesis. FSH acts directly on the Sertoli cells to stimulate germ cell number and acts indirectly to increase androgen production by the Leydig cells. In order to differentiate between the direct effects of FSH on spermatogenesis and those mediated indirectly through androgen action, we have crossed hypogonadal (hpg) mice, which lack gonadotrophins, with mice lacking androgen receptors (AR) either ubiquitously (ARKO) or specifically on the Sertoli cells (SCARKO). Thesehpg.ARKO andhpg.SCARKO mice were treated with recombinant FSH for 7 days and testicular morphology and cell numbers were assessed. In untreatedhpgandhpg.SCARKO mice, germ cell development was limited and did not progress beyond the pachytene stage. Inhpg.ARKO mice, testes were smaller with fewer Sertoli cells and germ cells compared tohpgmice. Treatment with FSH had no effect on Sertoli cell number but significantly increased germ cell numbers in all groups. Inhpgmice, FSH increased the numbers of spermatogonia and spermatocytes, and induced round spermatid formation. Inhpg.SCARKO andhpg.ARKO mice, in contrast, only spermatogonial and spermatocyte numbers were increased with no formation of spermatids. Leydig cell numbers were increased by FSH inhpgandhpg.SCARKO mice but not inhpg.ARKO mice. Results show that in rodents 1) FSH acts to stimulate spermatogenesis through an increase in spermatogonial number and subsequent entry of these cells into meiosis, 2) FSH has no direct effect on the completion of meiosis and 3) FSH effects on Leydig cell number are mediated through interstitial ARs.