论文成果
SphK-produced S1P in somatic cells is indispensable for LH-EGFR signaling-induced mouse oocyte maturation.
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发表刊物：
Cell Death & Disease
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刊物所在地：
UK
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摘要：
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.
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全部作者：
Yanying Cui,FuXin Huang,Xiaodan Zhang,Yanli Sun,Tiantian Hao,Zhijuan Wang,Wei Xia
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第一作者：
Feifei Yuan,Xiaoqiong Hao
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论文类型：
Research Article
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通讯作者：
Youqiang Su,Meijia Zhang
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论文编号：
10.1038/s41419-022-05415-2
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卷号：
13
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期号：
11
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页面范围：
963
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ISSN号：
2041-4889
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是否译文：
否
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发表时间：
2022-11-17
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