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

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 1st and 3rd trimester control and early onset preeclampsia (EOPE) pregnant women (n = 15) using pyrosequencing and qRT-PCR respectively.

RESULTS: In 1st trimester, PEG3 was significantly hypermethylated, whereas no significant methylation changes were noted in PEG10 and MEST in EOPE. In 3rd 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 1st trimester EOPE. However, in 3rd trimester significant increased expression in PEG10, PEG3 and DLK1 noted. MEST expression was reduced in 3rd trimester EOPE. No correlation was observed between average DNA methylation and gene expression in PEG10 and PEG3 in 1st trimester. However, in 3rd 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.