Epigenetic Placental Programming of Preeclampsia

Abstract

Preeclampsia (PE) affects 8–10% of women in the US and long‐term consequences include development of maternal hypertension and hypertension in offspring. As methylation patterns are established during fetal life, we focused on epigenetic alterations as a plausible explanation of the heritable development of hypertension resulting from maternal PE. In this proof‐of‐principle study we determined genome‐wide CpG DNA methylation patterns in placental tissue from women with normotensive pregnancy and PE (n=3/group) by using 2.1M microarrays (NimbleGen). These arrays tile 7000 bp upstream and 3000 bp downstream a promoter in 100 bp segments and cover 28000 CpG islands. Criteria for gene selection included methylation +/−1000 bp of the respective gene's transcription start site. We identified 163 genes methylated only in PE and uploaded them to DAVID (http://david.abcc.ncifcrf.gov) where we used a classification stringency of high to determine functional annotation clusters. Cluster 1had an enrichment score of 5.59; this cluster contains the GO Terms of anatomical structure formation, angiogenesis, blood vessel development, vasculature development, and blood vessel morphogenesis. There are 12 genes total in this cluster 10 of which are common to all 5 GO Terms. This work suggests that an epigenetic mechanism may be involved in PE.Robert Wood Johnson Nurse Faculty Scholar, Sigma Theta Tau International, ARS