Pre-eclampsia (PE) is a serious pregnancy disorder linked to genetic factors, particularly the ACVR2A gene, which encodes a receptor involved in the activin signaling pathway and plays a critical role in reproductive processes. Transcriptomic data analysis and experimental verification confirmed a downregulation of ACVR2A expression in placental tissues from PE patients. In this study, CRISPR/Cas9 technology was employed to investigate the effect of ACVR2A gene deletion on trophoblast cells using the HTR8/SVneo and JAR cell lines.. Deletion of ACVR2A inhibits trophoblastic migration, proliferation, and invasion, underscoring its pivotal role in cellular function. RNA-seq data analysis unveiled an intricate regulatory network influenced by ACVR2A gene knockout, especially in the TCF7/c-JUN pathway. By employing RT-PCR and immunohistochemical analysis, a potential association between ACVR2A and the TCF7/c-JUN pathway was hypothesized and confirmed. The complexity of PE onset and the significance of genetic factors were emphasized, particularly the role of the ACVR2A gene identified in GWAS. This study established a robust foundation for delving deeper into the intricate mechanisms of PE, paving the way for focused early intervention, personalized treatment, and enhanced obstetric healthcare.

The authors have declared no competing interest.

This study was supported by the Guangdong Basic and Applied Basic Research Fund (Guangdong-Shenzhen Joint Fund) (2021B1515120070, 2023A1515010872), the National Key R&D Program of China (2021YFC2701500, 2019YFA0110804), Guangzhou fundamental research project jointly funded by School (Institution)(high-level university) ( 202102010131)

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The Ethics Committee of The Third Affiliated Hospital of Guangzhou Medical University (Guangzhou, China) approved the experiments using human cells.

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