EGR1 modulates EPHB4-induced trophoblast dysfunction in recurrent spontaneous abortion†.

Abstract

Recurrent spontaneous abortion, defined as at least three unexplained abortions occurring before the 20-24 week of pregnancy, has a great impact on women's quality of life. Ephrin receptor B4 has been associated with trophoblast function in preeclampsia. The present study aimed to verify the hypothesis that ephrin receptor B4 regulates the biological functions of trophoblasts in recurrent spontaneous abortion and to explore the upstream mechanism. Ephrin receptor B4 was overexpressed in mice with recurrent spontaneous abortion. Moreover, ephrin receptor B4 inhibited trophoblast proliferation, migration, and invasion while promoting apoptosis. Downregulation of early growth response protein 1 expression in mice with recurrent spontaneous abortion led to ephrin receptor B4 overexpression. Poor expression of WT1-associated protein in mice with recurrent spontaneous abortion reduced the modification of early growth response protein 1 mRNA methylation, resulting in decreased early growth response protein 1 mRNA stability and expression. Overexpression of WT1-associated protein reduced the incidence of recurrent spontaneous abortion in mice by controlling the phenotype of trophoblasts, which was reversed by early growth response protein 1 knockdown. All in all, our findings demonstrate that dysregulation of WT1-associated protein contributes to the instability of early growth response protein 1, thereby activating ephrin receptor B4-induced trophoblast dysfunction in recurrent spontaneous abortion. Our study provides novel insights into understanding the molecular pathogenesis of recurrent spontaneous abortion.

• Authors: Rong Hua, Yi Mo, Xiu Lin, Bin Zhang, Min He, Chun Huang, Yujie Huang, Jie Li, Jiangfan Wan, Huamei Qin, Qinshan Xie, Donggui Zeng, Yan Sun
• Journal: Biology of reproduction (Biol Reprod) Vol. 110 Issue 3 Pg. 476-489 (Mar 13 2024) ISSN: 1529-7268 [Electronic] United States
• PMID: 38091979 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2023. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Early Growth Response Protein 1
• EGR1 protein, human
• Ephrins
• Ephb4 protein, mouse
• Egr1 protein, mouse

Topics

• Animals
• Female
• Humans
• Mice
• Pregnancy
• Abortion, Habitual (metabolism)
• Abortion, Spontaneous (genetics)
• Cell Movement
• Cell Proliferation
• Early Growth Response Protein 1
• Ephrins (metabolism)
• Quality of Life
• Trophoblasts (metabolism)