Widespread DNA hypomethylation at gene enhancer and low CpG density regions in placentas associated with early-onset preeclampsia

Abstract

s / Placenta 34 (2013) A1–A99 A86 P2.88. WIDESPREAD DNA HYPOMETHYLATION AT GENE ENHANCER AND LOW CPG DENSITY REGIONS IN PLACENTAS ASSOCIATEDWITH EARLY-ONSET PREECLAMPSIA John Blair , Ryan Yuen , Brendan Lim , Deborah McFadden , Peter von Dadelszen , Wendy Robinson 1 University of British Columbia, Vancouver, BC, Canada; University of Toronto, Toronto, ON, Canada Preeclampsia is a serious complication of pregnancy that can affect both maternal and fetal outcomes. Early-onset preeclampsia (EOPET) is a severe form of preeclampsia that is associated with altered physiological characteristics and gene expression in the placenta. DNA methylation is a relatively stable epigenetic modification to DNA that can reflect gene expression, and can provide insight into the mechanisms underlying such expression changes. Objectives: We sought to profile DNA methylation changes in EOPET to better characterize the pathology underlying this condition and the relationship to clinical features. Methods: DNA methylation was profiled in placentas from 20 EOPET and 20-gestational age matched control pregnancies using the Infinium HumanMethylation450 Beadchip. This analysis was followed up using the HT-12v4 Expression BeadChip microarray, bisulfite pyrosequencing and bioinformatic analysis. Results: We identified 38,840 CpG sites with significant (FDR 12.5% methylation difference compared to the gestational age-matched normotensive controls. Significant sites were enriched at the enhancers and low CpG density regions of the associated genes and the majority (74.5%) of these sites were hypomethylated in EOPET. No stratification of the EOPET DNA methylation profile was apparent based on presence/absence of intrauterine growth restriction (IUGR) or severe proteinuria. CpG sites from four genes relevant to preeclampsia (INHBA, BHLHE40, SLC2A1, and ADAM12) were followed up using bisulfite pyrosequencing in a larger cohort, and they showed different extent of changes in related pregnancy disorders (late-onset preeclampsia (LOPET) and normotensive IUGR (nIUGR)). Genome-wide expression in a subset of samples showed that some of the gene expression changes were negatively correlated with DNA methylation changes, particularly for genes that are responsible for angiogenesis (such as EPAS1 and FLT1). Conclusion: Based on DNA methylation profiling, we conclude that there are widespread DNA methylation alterations in EOPET that may be associated with changes in placental function. This property may provide a useful tool for early screening of such placentas. http://dx.doi.org/10.1016/j.placenta.2013.06.254 P2.89. MORPHOLOGY OF THE MOUSE MESOMETRIAL DECIDUA DURING EARLY PREGNANCY Alex Kors Vidsiunas , Sergio Ferreira de Oliveira 2 Nove de Julho University, Sao Paulo-SP, Brazil; University of Sao Paulo, Sao