MeCP2 Dysfunction in Decidual Stromal Cells is Related to Dysregulation of Decidualization

Abstract Objective: To investigate the role of decidual methyl-CpG-binding protein 2 ( MeCP2 ) expression in the pathogenesis of preeclampsia by comparing preeclamptic patients with normotensive pregnant controls, and to elucidate the underlying mechanisms through which this epigenetic regulator exerts its effects. Methods: Differentially expressed genes in the decidua of patients with preeclampsia were analyzed using single-cell sequencing. Target molecule expression was validated using western blotting, qPCR, and immunohistochemistry. Furthermore, the expression levels of DNA methyltransferase-related genes and decidualization markers were examined, and DNA 5-hydroxymethylcytosine (5-hmC) methylation levels were detected by enzyme-linked immunosorbent assay. To investigate the roles of decidualization and MeCP2 in preeclampsia, an in vitro model using human endometrial stromal cells (hESCs) was established. Decidualization was then induced, and MeCP2 was knocked down and the effects assessed. RNA sequencing was also used to analyze the effect of MeCP2 in hESCs. Results: MeCP2 expression was decreased in the decidua of patients with preeclampsia, accompanied by features indicative of decidualization defects. Aberrant DNA methylation levels, along with altered expression of DNA methyltransferase-related genes, were observed in the pre-eclamptic decidua, alongside an upregulation of DNA 5-hmC methylation levels. These findings suggest that an association exists between aberrant DNA methylation and impaired decidualization in preeclampsia. Further investigation revealed that the knockdown of MeCP2 in human endometrial stromal cells (hESCs) resulted in reduced decidualization capacity. Conclusion: In the preclamptic decidua, decreased expression of MeCP2 and aberrant DNA methylation are associated with defects in decidualization. Using an in vitro ESC model, MeCP2 was found to be associated with the decidualization process, wherein its knockdown resulted in characteristics of decidualization impairment.