OP 54 Early- and late-onset preeclampsia and the tissue-specific epigenome of the placenta and newborn

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Introduction Preeclampsia (PE) carries increased risks of cardiovascular- and metabolic diseases in mothers and offspring during the life course. While the severe early-onset PE (EOPE) phenotype originates from impaired placentation in early pregnancy, late-onset PE (LOPE) is in particular associated with pre-existing maternal cardiovascular- and metabolic risk factors. We hypothesize that PE is associated with altered epigenetic programming of placental and fetal tissues and that these epigenetic changes link both PE phenotypes with features of cardiovascular- and metabolic diseases in offspring. Objectives In this study we examined tissue-specific genome-wide DNA methylation of umbilical cord blood leucocytes (UC-WBC), placental tissue and human umbilical cord endothelial cells (HUVEC) in relation to EOPE and LOPE. Patients and methods A nested case-control study was conducted in The Rotterdam Periconceptional Cohort (Predict study) comprising 13 EOPE, 16 LOPE, and three control groups of 36 uncomplicated pregnancies, 27 normotensive fetal growth restricted and 20 normotensive preterm birth (PTB) complicated pregnancies. Placental tissue, UC-WBC and HUVEC were collected and DNA methylation of cytosine-guanine dinucleotides was measured by the Illumina HumanMethylation450K BeadChip. An epigenome-wide analysis was performed by using multiple linear regression models. Results Epigenome-wide analysis revealed significant differences only between tissues from EOPE and PTB controls, with 5001 mostly hypermethylated differentially methylated positions (DMPs) in UC-WBC and 869 mostly hypomethylated DMPs in placental tissue, situated in or close to genes associated with cardiovascular system developmental pathways. (Fig. 1. Density plot of β -values per tissue and per group). (Fig. 2. Heatmap based on clustering of methylation ( β -value) of all differentially methylated CpGs). Conclusion This study shows differential methylation in UC-WBC and placental tissue in EOPE as compared to PTB, identifying DMPs that are associated with cardiovascular system pathways. Future studies should examine these loci and pathways in more detail to elucidate the associations between prenatal PE exposure and the cardiovascular disease risk in offspring. Download : Download high-res image (160KB) Download : Download full-size image Download : Download high-res image (215KB) Download : Download full-size image