Abstract
Mechanistic target of rapamycin complex 1 (mTORC1) plays crucial roles in male fertility. In mammals, deregulation of mTORC1 led to disordered spermatogonia proliferation and spermatogenesis, which eventually caused infertility in males. However, its roles in male fertility of non-mammalian species remain unclarified. In the present study, it was found that treatment of rapamycin, an mTORC1 inhibitor, resulted in infertility with decreased milt production and sperm motility in zebrafish. However, it is surprising to find that spermatogenesis was normal in these fish. All types of germ cells were found and the proliferation of spermatogonia and spermatocyte were normal. These results suggested that maturation of sperm may be impaired in males treated with rapamycin. Increased apoptosis was found surrounding the lumen containing spermatozoa, implicating a loss of Sertoli cells in testes treated with rapamycin. Moreover, LH/hCG mediated up-regulation of steroidogenic genes was abolished. The expression of npr and ar induced by LH/hCG was also blocked, which further suppressed the signaling of progestin and androgen. Collectively, mTORC1 maintains male fertility via different mechanisms in fish and mammals. mTORC1 is dispensable for spermatogenesis in zebrafish, but possibly supports the maintenance of Sertoli cells and mediates the signaling of hormones, which are crucial for sperm maturation.