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

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

Journal:Proc Natl Acad Sci USA

Place of Publication:USA

Key Words:Sertoli-like cells; female infertility; granulosa cell; meiosis; oocyte-expressed MTOR

Summary: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.

First Author:Jing Guo

Correspondence Author:You-Qiang Su

All the Authors: John J Eppig, Jiahao Sha, Xuejiang Guo, Lanying Shi, Hao Wang, Yaoxue Yin, Guangyi Cao, Hong Yin, Xiaoyun Zhang, Hui Li, Tao Sun, Yueshuai Guo,Teng Zhang

Document Code:10.1073/pnas.1800352115

Volume:115

Issue:23

Page Number:E5326-E5333

ISSN:1091-6490

Translation or Not:No

Date of Publication:2018-05

Release Time:2025-04-30