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

Authors

Jing Guo
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, The Jackson LaboratoryFollow
You-Qiang Su

Document Type

Article

Publication Date

6-5-2018

JAX Source

Proc Natl Acad Sci U S A 2018 Jun 5; 115(23):E5326-E5333.

Volume

115

Issue

23

First Page

5326

Last Page

5326

ISSN

1091-6490

PMID

29784807

DOI

https://doi.org/10.1073/pnas.1800352115

Abstract

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. Proc Natl Acad Sci U S A 2018 Jun 5; 115(23):E5326-E5333.

Comments

This open access article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)

Recommended Citation

Guo J, Zhang T, Guo Y, Sun T, Li H, Zhang X, Yin H, Cao G, Yin Y, Wang H, Shi L, Guo X, Sha J, Eppig JJ, Su Y. Oocyte stage-specific effects of MTOR determine granulosa cell fate and oocyte quality in mice. Proc Natl Acad Sci U S A 2018 Jun 5; 115(23):E5326-E5333.