Oocyte stage-specific effects of MTOR determine granulosa cell fate and oocyte quality in mice.

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Proceedings of the National Academy of Sciences of the United States of America, ISSN: 1091-6490, Vol: 115, Issue: 23, Page: E5326-E5333

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Guo, Jing; Zhang, Teng; Guo, Yueshuai; Sun, Tao; Li, Hui; Zhang, Xiaoyun; Yin, Hong; Cao, Guangyi; Yin, Yaoxue; Wang, Hao; Shi, Lanying; Guo, Xuejiang; Sha, Jiahao; Eppig, John J; Su, You-Qiang Show More Hide
Proceedings of the National Academy of Sciences; National Academy of Sciences
Multidisciplinary; Life Sciences; Medicine and Health Sciences
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June 19, 2018 | Bio360 by 陈席元

中国科学家近日研究发现,一种名为 mtor 的基因对女性能否排出正常健康的卵子起决定作用。 据南京医科大学苏友强教授团队的张滕博士介绍,mtor 基因能够“生产”一种关键因子 MTOR,负责维持营养和应激感应的信号通路。 研究人员尝试在雌鼠卵泡发育的各个阶段敲除 mtor ...

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article description
MTOR (mechanistic target of rapamycin) is a widely recognized integrator of signals and pathways key for cellular metabolism, proliferation, and differentiation. Here we show that conditional knockout (cKO) of in either primordial or growing oocytes caused infertility but differentially affected oocyte quality, granulosa cell fate, and follicular development. cKO of in nongrowing primordial oocytes caused defective follicular development leading to progressive degeneration of oocytes and loss of granulosa cell identity coincident with the acquisition of immature Sertoli cell-like characteristics. Although was deleted at the primordial oocyte stage, DNA damage accumulated in oocytes during their later growth, and there was a marked alteration of the transcriptome in the few oocytes that achieved the fully grown stage. Although oocyte quality and fertility were also compromised when was deleted after oocytes had begun to grow, these occurred without overtly affecting folliculogenesis or the oocyte transcriptome. Nevertheless, there was a significant change in a cohort of proteins in mature oocytes. In particular, down-regulation of PRC1 (protein regulator of cytokinesis 1) impaired completion of the first meiotic division. Therefore, MTOR-dependent pathways in primordial or growing oocytes differentially affected downstream processes including follicular development, sex-specific identity of early granulosa cells, maintenance of oocyte genome integrity, oocyte gene expression, meiosis, and preimplantation developmental competence.