Reduced ELABELA expression attenuates trophoblast invasion through the PI3K/AKT/mTOR pathway in early onset preeclampsia

Abstract

Introduction: Early onset preeclampsia is linked to abnormal trophoblast invasion, leading to insufficient recasting of uterine spiral arteries and shallow placental implantation. This study investigated ELABELA (ELA) expression and its involvement in the pathogenesis of early onset preeclampsia.

Methods: We used immunohistochemistry, quantitative PCR and Western blot to calculate ELA levels in the placentas. Transwell assays were utilize to assess the invasion and migration of trophoblastic Cells. Western blot was used to identify the concentrations of vital kinases in PI3K/AKT/mTOR pathways and invasion-related proteins in trophoblast cells.

Results: ELA was expressed in villous cytotrophoblasts and syncytiotrophoblasts in placental tissue. Compared with the normal pregnancies, ELA mRNA and protein expression was significantly reduced in early onset preeclampsia placentas. In the HTR-8/SVneo cells, when ELA was knocked down, the invasion and migration capability of cells decreased significantly, with MMP2 and MMP9 expression downregulated and the expression of important kinases in the PI3K/AKT/mTOR pathways being significantly decreased compared to the control group. Overexpression of ELA was on the contrary. Besides, while PI3K was blocked, the invasion and migration capability of HTR-8/SVneo cells and the expression of key kinases in PI3K/AKT/mTOR pathways were decreased significantly.

Discussion: ELA stimulates the invasion and migration of trophoblastic cells through activation of downstream PI3K/AKT/mTOR pathway and is complicit in early onset preeclampsia pathogenesis. Our research offers a potential novel treatment for PE.

Keywords: AKT; ELA; Invasion; PI3K; Preeclampsia.