Bioinformatics study and experimental validation of METTL3 regulation of immune-related genes affecting placental vascular development

The proper development of the placental vascular system is a crucial factor in ensuring fetal health. m6A modification is a key pathophysiological mechanism in placental vascular development. However, the specific mechanism by which m6A influences placental vascular development remains unclear. Here, we explored the role of 21 m6A regulators in placental development based on the Gene Expression Omnibus (GEO) database. Following a series of machine learning techniques, METTL3 was recognized as the pivotal m6A regulator. We subsequently employed consensus clustering analysis to delineate two distinct m6A isoforms, and investigated their correlation with immune cells. Further, through weighted gene co-expression network analysis (WGCNA) coupled with correlation analysis, we pinpointed METTL3-associated placental development genes. These genes were notably enriched in immune-related categories. Furthermore, we uncovered immune-related differentially expressed genes that were associated with differentially expressed m6A regulators. Additionally, we performed an immune infiltration analysis to gain a deeper understanding of how these genes interact with immune cells. Ultimately, to validate our findings, we carried out animal experiments. In conclusion, our study found that targeting METTL3 could affect placental vascular development, which may provide guidance for the clinical treatment of placental-like diseases.