mTOR与卵泡发育

原始卵泡由单层扁平前颗粒细胞包围卵母细胞形成,是女性的基本生殖单位,其数目在胎儿期就已决定。随着年龄的增长,原始卵泡数量不断减少,其数目一定程度上代表了女性生育年限的长短。而哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)与细胞生长发育密切相关。在静止期卵母细胞与前颗粒细胞中,mTOR表达异常可导致细胞内蛋白合成增加,卵母细胞发育及颗粒细胞分裂、分化,使原始卵泡被激活,引发原始卵泡库过早耗竭,从而导致女性卵巢储备能力降低、生育年限缩短。近年来,mTOR及其介导的信号通路作为女性生育力保护的潜在靶点已成为生殖医学领域的研究热点。其对卵泡发育的调节作用,将为延缓女性卵巢衰老提供新思路。现从哺乳动物原始卵泡激活及其与mTOR信号网络的相关性等方面进行综述,并探讨其与女性不孕的关系。

mTOR with the Follicular Development

Primordial follicle, as a basic unit of female reproduction, consist of oocyte and its surrounding a layer of flat granulosa cells. The primordial follicle pool has already been established in fetus. The number of primordial follicles is continuously decreasing with age, this pool therefore represents the female reproductive lifespan. It has been proved that mammalian target of rapamycin (mTOR) play a critical role in cellular growth and development. The excessive expression of mTOR activates the protein synthesis in dormant oocytes and pregranulosa cells, and subsequently induces the over-activation of primordial follicles, leading to the exhaustion of the promordial follicle pool, the decline of ovarian reserve and the decurtation of female reproductive lifespan. Recent years, mTOR, as well as the mediated signaling pathway, have become a hotspot in the field of reproductive medicine as the potential targets. The regulation of mTOR on follicle development could provide new strategies for delaying ovarian aging. In this article，the activation of mammalian primordial follicle and its relationship to mTOR signaling networks were reviewed, and the possible relationship between mTOR and female infertility was discussed.