The ovarian follicle pool size is limited; it decreases with age and following germ cell-damaging chemo- or radiation therapies. Due to a trend of delaying child-bearing age in the modern society, it is important to investigate the possibility to maintain the follicle reserve for middle-aged women and cancer-bearing patients subject to therapies. Earlier studies demonstrated the important role of the mammalian targets of the rapamycin (MTOR) signaling pathway in the activation of primordial follicles and suggested that treatment with the MTOR inhibitor rapamycin could maintain the follicle pool in rodents. Here, we confirmed the ability of rapamycin treatment for 3 weeks to suppress primordial follicle development and to maintain follicle pool size in mice. We further demonstrated that the developmental potential of oocytes was not affected by rapamycin treatment and the effect of rapamycin to decrease initial follicle recruitment is reversible. Using human ovarian cortical fragments grafted into immune-deficient mice, we demonstrated the ability of rapamycin to suppress follicle growth from the primordial stage. Our studies provide the basis for further studies on the possibility of using MTOR inhibitors to maintain follicle reserve in middle-aged women and cancer patients before/during germ cell-damaging therapies.

中文翻译：

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雷帕霉素治疗维持了小鼠卵母细胞的发育潜力以及移植到免疫缺陷小鼠的人皮层碎片中的卵泡储备。

卵巢卵泡池的大小是有限的。随着年龄的增长以及对生殖细胞的破坏性化学疗法或放射疗法的治疗，它会降低。由于现代社会中推迟生育年龄的趋势，重要的是研究维持中年妇女和接受治疗的癌症患者的卵泡储备的可能性。较早的研究表明，雷帕霉素（MTOR）信号转导途径的哺乳动物靶标在原始卵泡的激活中起着重要作用，并建议用MTOR抑制剂雷帕霉素进行治疗可以维持啮齿动物的卵泡库。在这里，我们证实了雷帕霉素治疗3周具有抑制原始卵泡发育并维持小鼠卵泡池大小的能力。我们进一步证明，雷帕霉素治疗不会影响卵母细胞的发育潜能，雷帕霉素降低初始卵泡募集的作用是可逆的。使用人类卵巢皮质片段移植到免疫缺陷小鼠中，我们证明了雷帕霉素从原始阶段抑制卵泡生长的能力。我们的研究为进一步研究有关在生殖细胞破坏疗法之前/期间使用MTOR抑制剂维持中年妇女和癌症患者卵泡储备的可能性的基础。