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

• Published in: Cell death & disease 2022-11, Vol.13 (11), p.963-963, Article 963
• Main Authors: Yuan, Feifei, Hao, Xiaoqiong, Cui, Yanying, Huang, FuXin, Zhang, Xiaodan, Sun, Yanli, Hao, Tiantian, Wang, Zhijuan, Xia, Wei, Su, Youqiang, Zhang, Meijia
• Format: Article
• Language: English
• Subjects: 13/1; 13/51; 13/95; 14/19; 38/91; 45/22; 45/90; 631/443/494/2732; 631/443/494/2732/1577; 64/110; 64/60; 82/58; AKT protein; Animals; Antibodies; Atrial natriuretic peptide; Biochemistry; Biomedical and Life Sciences; Cell activation; Cell Biology; Cell Culture; Cell differentiation; Cell division; Epidermal growth factor; Epidermal Growth Factor - metabolism; Epidermal Growth Factor - pharmacology; Epidermal growth factor receptors; ErbB Receptors - genetics; ErbB Receptors - metabolism; Female; Immunology; Infertility; Life Sciences; Luteinizing hormone; Luteinizing Hormone - metabolism; Maturation; Meiosis; Mice; Natriuretic Peptides - metabolism; Oocytes; Oocytes - metabolism; Oogenesis; Peptides; Phosphotransferases (Alcohol Group Acceptor); Somatic cells; TOR protein
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-022-05415-2

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.