Oocyte-dependent activation of MTOR in cumulus cells controls the development and survival of cumulus-oocyte complexes.

Journal:J Cell Sci

Place of Publication:UK

Key Words:Apoptosis; Cumulus cells; DDIT4L; Female infertility; MTOR; Oocyte

Abstract:Communication between oocytes and their companion somatic cells promotes the healthy development of ovarian follicles, which is crucial for producing oocytes that can be fertilized and are competent to support embryogenesis. However, how oocyte-derived signaling regulates these essential processes remains largely undefined. Here, we demonstrate that oocyte-derived paracrine factors, particularly GDF9 and GDF9-BMP15 heterodimer, promote the development and survival of cumulus-cell-oocyte complexes (COCs), partly by suppressing the expression of Ddit4l, a negative regulator of MTOR, and enabling the activation of MTOR signaling in cumulus cells. Cumulus cells expressed less Ddit4l mRNA and protein than mural granulosa cells, which is in striking contrast to the expression of phosphorylated RPS6 (a major downstream effector of MTOR). Knockdown of Ddit4l activated MTOR signaling in cumulus cells, whereas inhibition of MTOR in COCs compromised oocyte developmental competence and cumulus cell survival, with the latter likely to be attributable to specific changes in a subset of transcripts in the transcriptome of COCs. Therefore, oocyte suppression of Ddit4l expression allows for MTOR activation in cumulus cells, and this oocyte-dependent activation of MTOR signaling in cumulus cells controls the development and survival of COCs.

All the Authors:Lanying Shi, Xuhong Gong, Mengjie Jiang, Yaoxue Yin, Xiaoyun Zhang, Hong Yin, Hui Li, Chihiro Emori, Koji Sugiura, John J Eppig

First Author:Jing Guo

Indexed by:Research Article

Correspondence Author:You-Qiang Su

Document Code:10.1242/jcs.182642

Volume:129

Issue:16

Page Number:3091-103

ISSN No.:1477-9137

Translation or Not:no

Date of Publication:2016-08-15

Date of Publication:2016-08-15