SphK-produced S1P in somatic cells is indispensable for LH-EGFR signaling-induced mouse oocyte maturation
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)...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2022-11-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-022-05415-2 |
| _version_ | 1797983934296883200 |
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| author | Feifei Yuan Xiaoqiong Hao Yanying Cui FuXin Huang Xiaodan Zhang Yanli Sun Tiantian Hao Zhijuan Wang Wei Xia Youqiang Su Meijia Zhang |
| author_facet | Feifei Yuan Xiaoqiong Hao Yanying Cui FuXin Huang Xiaodan Zhang Yanli Sun Tiantian Hao Zhijuan Wang Wei Xia Youqiang Su Meijia Zhang |
| author_sort | Feifei Yuan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T06:54:58Z |
| format | Article |
| id | doaj.art-cbde64a8ab3845ff8dac98848f196749 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-11T06:54:58Z |
| publishDate | 2022-11-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-cbde64a8ab3845ff8dac98848f1967492022-12-22T04:39:04ZengNature Publishing GroupCell Death and Disease2041-48892022-11-01131111110.1038/s41419-022-05415-2SphK-produced S1P in somatic cells is indispensable for LH-EGFR signaling-induced mouse oocyte maturationFeifei Yuan0Xiaoqiong Hao1Yanying Cui2FuXin Huang3Xiaodan Zhang4Yanli Sun5Tiantian Hao6Zhijuan Wang7Wei Xia8Youqiang Su9Meijia Zhang10Division of Cell, Developmental and Integrative Biology, School of Medicine, South China University of TechnologyDivision of Cell, Developmental and Integrative Biology, School of Medicine, South China University of TechnologyDivision of Cell, Developmental and Integrative Biology, School of Medicine, South China University of TechnologyDivision of Cell, Developmental and Integrative Biology, School of Medicine, South China University of TechnologyDivision of Cell, Developmental and Integrative Biology, School of Medicine, South China University of TechnologyDivision of Cell, Developmental and Integrative Biology, School of Medicine, South China University of TechnologyDivision of Cell, Developmental and Integrative Biology, School of Medicine, South China University of TechnologyDivision of Cell, Developmental and Integrative Biology, School of Medicine, South China University of TechnologyDepartment of Reproductive Medicine Centre, Guangzhou First People’s Hospital, South China University of TechnologyShandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong UniversityDivision of Cell, Developmental and Integrative Biology, School of Medicine, South China University of TechnologyAbstract 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.https://doi.org/10.1038/s41419-022-05415-2 |
| spellingShingle | Feifei Yuan Xiaoqiong Hao Yanying Cui FuXin Huang Xiaodan Zhang Yanli Sun Tiantian Hao Zhijuan Wang Wei Xia Youqiang Su Meijia Zhang SphK-produced S1P in somatic cells is indispensable for LH-EGFR signaling-induced mouse oocyte maturation Cell Death and Disease |
| title | SphK-produced S1P in somatic cells is indispensable for LH-EGFR signaling-induced mouse oocyte maturation |
| title_full | SphK-produced S1P in somatic cells is indispensable for LH-EGFR signaling-induced mouse oocyte maturation |
| title_fullStr | SphK-produced S1P in somatic cells is indispensable for LH-EGFR signaling-induced mouse oocyte maturation |
| title_full_unstemmed | SphK-produced S1P in somatic cells is indispensable for LH-EGFR signaling-induced mouse oocyte maturation |
| title_short | SphK-produced S1P in somatic cells is indispensable for LH-EGFR signaling-induced mouse oocyte maturation |
| title_sort | sphk produced s1p in somatic cells is indispensable for lh egfr signaling induced mouse oocyte maturation |
| url | https://doi.org/10.1038/s41419-022-05415-2 |
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