Methylation and expression of imprinted genes in circulating extracellular vesicles from women experiencing early onset preeclampsia

Abstract

Introduction

Preeclampsia (PE) is a pregnancy complication marked by high blood pressure, posing risk to maternal and fetal health. "Genomic imprinting", an epigenetic phenomenon regulated by DNA methylation at Differently Methylated Regions (DMR's), influences placental development. Research on circulating extracellular vesicles (EVs) in PE suggests them as potential source for early biomarkers, but methylation status of EV-DNA in Preeclampsia is not reported yet.

Methods

This study examines the methylation and expression profile of imprinted genes - PEG10, PEG3, MEST, and DLK1 in circulating EVs of 1^st and 3^rd trimester control and early onset preeclampsia (EOPE) pregnant women (n = 15) using pyrosequencing and qRT-PCR respectively.

Results

In 1^st trimester, PEG3 was significantly hypermethylated, whereas no significant methylation changes were noted in PEG10 and MEST in EOPE. In 3^rd trimester, significant hypomethylation in PEG10, PEG3 and IGDMR was observed whereas significant hypermethyaltion noted in MEST. mRNA expression of PEG10, PEG3 and DLK1 was not affected in circulating EVs of 1^st trimester EOPE. However, in 3^rd trimester significant increased expression in PEG10, PEG3 and DLK1 noted. MEST expression was reduced in 3^rd trimester EOPE. No correlation was observed between average DNA methylation and gene expression in PEG10 and PEG3 in 1^st trimester. However, in 3^rd trimester, significant negative correlation was noted in PEG10 (r = −0.426, p = 0.04), PEG3 (r = −0.496, p = 0.01), MEST (r = −0.398, p = 0.03) and DLK1 (r = −0.403, p = 0.03).

Discussion

The results of our study strengthen the potential of circulating EVs from maternal serum as non-invasive indicators of placental pathophysiology, including preeclampsia.