论文成果
Oocyte stage-specific effects of MTOR determine granulosa cell fate and oocyte quality in mice.
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发表刊物:
Proc Natl Acad Sci USA
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刊物所在地:
USA
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关键字:
Sertoli-like cells; female infertility; granulosa cell; meiosis; oocyte-expressed MTOR
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摘要:
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 Mtor in either primordial or growing oocytes caused infertility but differentially affected oocyte quality, granulosa cell fate, and follicular development. cKO of Mtor 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 Mtor 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 Mtor 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.
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全部作者:
Teng Zhang, Yueshuai Guo, Tao Sun, Hui Li, Xiaoyun Zhang, Hong Yin, Guangyi Cao, Yaoxue Yin, Hao Wang, Lanying Shi, Xuejiang Guo, Jiahao Sha, John J Eppig
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第一作者:
Jing Guo
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论文类型:
Research Article
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通讯作者:
You-Qiang Su
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论文编号:
10.1073/pnas.1800352115
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卷号:
115
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期号:
23
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页面范围:
E5326-E5333
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ISSN号:
1091-6490
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是否译文:
否
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发表时间:
2018-05-21
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下一条:Oocyte-dependent activation of MTOR in cumulus cells controls the development and survival of cumulus-oocyte complexes.