AQP3 Influences Unexplained Recurrent Abortion by Regulating Trophoblast Cell Migration and Invasion via the METTL14/IGF2BP1/AQP3/PI3K/AKT Pathway

Abstract

Reduced trophoblast migration and invasion contribute to unexplained recurrent spontaneous abortion (URSA). Aquaporin 3 (AQP3) plays a crucial role in facilitating trophoblast migration and invasion during early pregnancy through fetal-maternal crosstalk. This study aimed to comprehensively investigate the mechanism involving AQP3 and its modulatory effects on human extravillous trophoblast (HTR-8/SVneo cells) migration and invasion. AQP3 and IGF2BP1 expression was analysed using immunohistochemistry and quantitative real-time polymerase chain reaction. The AQP3-associated molecular mechanisms were explored using western blot, meRIP, RNA stability assays and RNA-protein pull-down experiments. Furthermore, the role of IGF2BP1 in HTR-8/SVneo cells was assessed using transwell assays. AQP3 and IGF2BP1 expression was lower in the chorionic villi samples of the URSA group than in those of the control group. AQP3 was involved in regulating the activation of the PI3K/AKT signalling pathway. Additionally, METTL14 interacted with AQP3 mRNA, thereby influencing its stability. Furthermore, AQP3 mRNA bound to the IGF2BP1 protein, and IGF2BP1 knockdown resulted in reduced AQP3 mRNA stability and impaired trophoblast migration and invasion. METTL14 and IGF2BP1 stabilise AQP3 mRNA expression by mediating m6A, thereby facilitating HTR-8/SVneo cell migration and invasion via the PI3K/AKT signalling pathway. Targeting AQP3 could potentially contribute to strategies aimed at mitigating URSA development.