Promoter hypomethylation and increased maspin expression in preeclamptic placentas in a Chinese population

Abstract

Objective: Preeclampsia is thought to begin with shallow trophoblast invasion and inadequate spiral artery remodeling. Maspin, a tumor-suppressor gene, plays a regulatory role in trophoblast invasion and motility. The tissue-specific methylation of the maspin promoter can regulate maspin gene expression in various cancers. We sought to detect maspin gene expression and assess the degrees of methylation of maspin promoter regions in preeclamptic placentas in the Han Chinese population and to investigate the potential role of maspin in the pathophysiology of preeclampsia.

Methods: We conducted RT-PCR, immunohistochemistry and western blotting to characterize maspin gene expression and protein levels in the placentas from normal and preeclamptic pregnancies. Finally, using methylation-specific PCR and bisulfite sequencing PCR, we detected the degrees of methylation of the promoter regions of maspin in each of the two studied groups.

Results: Maspin expression was increased at the mRNA and protein levels in the preeclamptic placentas compared to the control group. Maspin immunohistochemical staining revealed positive staining in the syncytio-cytotrophoblast layers and more diffuse staining in the preeclamptic group. The mean methylation level of the analyzed promoter region was significantly hypomethylated in the preeclamptic placentas compared to the control placentas, pointing to a negative relationship between maspin promoter methylation and gene expression.

Discussion: Hypomethylation of the maspin promoter results in increased expression of maspin in preeclamptic placentas, which suggests a negative relationship between maspin methylation and maspin expression in this Han Chinese population. Thus, maspin is likely involved in the etiology of preeclampsia.

Keywords: Maspin; Placenta; Preeclampsia; Promoter methylation.