2. Academic Validation
  3. EGR1 modulates EPHB4-induced trophoblast dysfunction in recurrent spontaneous abortion

EGR1 modulates EPHB4-induced trophoblast dysfunction in recurrent spontaneous abortion

  • Biol Reprod. 2023 Dec 13:ioad169. doi: 10.1093/biolre/ioad169.
Rong Hua 1,  Yi Mo 2,  Xiu Lin 3,  Bin Zhang 3,  Min He 4,  Chun Huang 5,  Yujie Huang 3,  Jie Li 5,  Jiangfan Wan 5,  Huamei Qin 5,  Qinshan Xie 6,  Donggui Zeng 6,  Yan Sun 7
Affiliations

Affiliations

  • 1 Department of Science and Education, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning 530005, Guangxi Zhuang Autonomous Region, P.R. China.
  • 2 Department of Science and Education, The Reproductive Hospital of Guangxi Zhuang Autonomous Region, Nanning 530029, Guangxi Zhuang Autonomous Region, P.R. China.
  • 3 Department of Gynecology, The Reproductive Hospital of Guangxi Zhuang Autonomous Region, Nanning 530029, Guangxi Zhuang Autonomous Region, P.R. China.
  • 4 Department of Clinical Laboratory, The Reproductive Hospital of Guangxi Zhuang Autonomous Region, Nanning 530029, Guangxi Zhuang Autonomous Region, P.R. China.
  • 5 Department of Reproductive Medicine, The Reproductive Hospital of Guangxi Zhuang Autonomous Region, Nanning 530029, Guangxi Zhuang Autonomous Region, P.R. China.
  • 6 Graduate School, Guangxi Medical University, Nanning 530000, Guangxi Zhuang Autonomous Region, P.R. China.
  • 7 Administrative office, The Reproductive Hospital of Guangxi Zhuang Autonomous Region, Nanning 530029, Guangxi Zhuang Autonomous Region, P.R. China.
PMID: 38091979 DOI: 10.1093/biolre/ioad169
Abstract

Recurrent spontaneous abortion (RSA), defined as at least three unexplained abortions occurring before the 20th week of pregnancy, has a great impact on women's quality of life. Ephrin Receptor B4 (EphB4) has been associated with trophoblast function in preeclampsia. The present study aimed to verify the hypothesis that EphB4 regulates the biological functions of trophoblasts in RSA and to explore the upstream mechanism. EphB4 was overexpressed in RSA mice. Moreover, EphB4 inhibited trophoblast proliferation, migration, and invasion while promoting Apoptosis. Downregulation of early growth response protein 1 (EGR1) expression in RSA mice led to EphB4 overexpression. Poor expression of WT1-associated protein (WTAP) in RSA mice reduced the modification of EGR1 mRNA methylation, resulting in decreased EGR1 mRNA stability and expression. Overexpression of WTAP reduced the incidence of RSA in mice by controlling the phenotype of trophoblasts, which was reversed by EGR1 knockdown. All in all, our findings demonstrate that dysregulation of WTAP contributes to the instability of EGR1, thereby activating EPHB4-induced trophoblast dysfunction in RSA. Our study provides novel insights into understanding the molecular pathogenesis of RSA.

Keywords

EGR1; EPHB4; Recurrent spontaneous abortion; Trophoblasts; WTAP.

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