SphK-produced S1P in somatic cells is indispensable for LH-EGFR signaling-induced mouse oocyte maturation.
SphK-produced S1P in somatic cells is indispensable for LH-EGFR signaling-induced mouse oocyte maturation.
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体细胞中 SphK 产生的 S1P 对于 LH-EGFR 信号诱导的小鼠卵母细胞成熟是必不可少的
DOI：
10.1038/s41419-022-05415-2
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发表时间：
2022-11-17
影响因子：
9
通讯作者：
Zhang, Meijia
中科院分区：
文献类型：
--
作者：
Yuan, Feifei;Hao, Xiaoqiong;Cui, Yanying;Huang, Fuxin;Zhang, Xiao;Sun, Yanli;Hao, Tiantian;Wang, Zhijuan;Xia, Wei;Su, Youqiang;Zhang, Meijia
生殖细胞的分裂和分化需要与周围的体细胞密切接触和相互作用。促黄体生成素（LH）触发类表皮生长因子（EGF）样生长因子，通过激活体细胞中的表皮生长因子受体（EGFR）来促进卵母细胞成熟和发育能力。在此，我们发现LH - EGFR信号在体细胞中激活鞘氨醇激酶（SphK）。EGF对EGFR的激活增加了卵丘 - 卵母细胞复合体（COCs）中S1P和钙的水平，并降低了利钠肽受体2（NPR2）与C型利钠肽（NPPC）的结合亲和力，从而解除了cGMP介导的减数分裂阻滞。EGF的这些功能被SphK抑制剂SKI - II阻断，而添加S1P可逆转这种阻断作用。S1P还激活了卵母细胞中的Akt/mTOR级联反应，并促进了Xklp2靶向蛋白（TPX2）的积累和卵母细胞发育能力。特异性地耗竭体细胞中的Sphk1/2会降低S1P水平，损害卵母细胞减数分裂成熟和发育能力，导致完全的雌性不育。总之，体细胞中SphK产生的S1P作为LH - EGFR信号从体细胞到卵母细胞的功能性传递物：作用于体细胞以诱导卵母细胞减数分裂成熟，并作用于卵母细胞以提高卵母细胞发育能力。
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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影响因子：
3.7
作者：
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