SphK-produced S1P in somatic cells is indispensable for LH-EGFR signaling-induced mouse oocyte maturation.

Journal:Cell Death & Disease

Place of Publication:UK

Abstract:Germ cell division and differentiation require intimate contact and interaction with the surrounding somatic cells. Luteinizing hormone (LH) triggers epidermal growth factor (EGF)-like growth factors to promote oocyte maturation and developmental competence by activating EGF receptor (EGFR) in somatic cells. Here, we showed that LH-EGFR signaling-activated sphingosine kinases (SphK) in somatic cells. The activation of EGFR by EGF increased S1P and calcium levels in cumulus-oocyte complexes (COCs), and decreased the binding affinity of natriuretic peptide receptor 2 (NPR2) for natriuretic peptide type C (NPPC) to release the cGMP-mediated meiotic arrest. These functions of EGF were blocked by the SphK inhibitor SKI-II, which could be reversed by the addition of S1P. S1P also activated the Akt/mTOR cascade reaction in oocytes and promoted targeting protein for Xklp2 (TPX2) accumulation and oocyte developmental competence. Specifically depleting Sphk1/2 in somatic cells reduced S1P levels and impaired oocyte meiotic maturation and developmental competence, resulting in complete female infertility. Collectively, SphK-produced S1P in somatic cells serves as a functional transmitter of LH-EGFR signaling from somatic cells to oocytes: acting on somatic cells to induce oocyte meiotic maturation, and acting on oocytes to improve oocyte developmental competence.

All the Authors:Yanying Cui,FuXin Huang,Xiaodan Zhang,Yanli Sun,Tiantian Hao,Zhijuan Wang,Wei Xia

First Author:Feifei Yuan,Xiaoqiong Hao

Indexed by:Research Article

Correspondence Author:Youqiang Su,Meijia Zhang

Document Code:10.1038/s41419-022-05415-2

Volume:13

Issue:11

Page Number:963

ISSN No.:2041-4889

Translation or Not:no

Date of Publication:2022-11-17

Date of Publication:2022-11-17