DNMT3a mediates FSTL3 methylation to regulate trophoblast proliferation, migration and invasion.

The substantial incidence and mortality rates of preeclampsia (PE) have drawn significant international attention. DNA methyltransferase 3a (DNMT3a) plays a pivotal role in DNA methylation processes, influencing the expression of specific genes. Research has demonstrated that DNMT3a expression levels are markedly diminished in the placental tissues of patients with PE. However, the precise functions and regulatory mechanisms of DNMT3a in PE are still not well-defined. The expression levels of DNMT3a and FSTL3 in placental tissues of preeclampsia (PE) patients were analyzed by quantitative PCR (qPCR) and Western blot. The effects of DNMT3a or FSTL3 overexpression on the proliferation, migration, and invasion of trophoblast cells were evaluated through CCK-8, scratch, and Transwell assays. Methylation-specific PCR (MSP) and dual-luciferase reporter gene assays were used to elucidate the role of DNMT3a in the methylation regulation of the FSTL3 promoter region. Western blot analysis showed that DNMT3a expression was downregulated and FSTL3 expression was upregulated in placental tissues of PE patients. DNMT3a overexpression promoted trophoblast proliferation, migration, and invasion, while FSTL3 overexpression inhibited these functions. Methylation-specific PCR and dual-luciferase assays revealed that DNMT3a suppressed FSTL3 expression via methylation. Subsequent experiments demonstrated that FSTL3 overexpression reversed the enhanced trophoblast proliferation, migration, and invasion induced by DNMT3a overexpression. DNMT3a promotes the proliferation, migration, and invasion of trophoblast cells, whereas overexpression of FSTL3 inhibits these cellular functions.