O7. Epigenome of the circadian clock pathway of placental and newborn tissues in pre-eclampsia

Abstract

Introduction The placenta is important in providing a healthy environment for the fetus and plays a central role in the pathophysiology of pre-eclampsia (PE). The circadian rhythm is implicated in fetal and placental growth and development. We hypothesize that derangements in prenatal epigenetic programming of circadian clock-related genes in placental and newborn tissues are associated with disease severity of PE. Objectives To investigate DNA methylation programming of circadian clock-related genes in patients with early-onset or late-onset PE and controls. Methods From the Rotterdam periconception cohort, patients with early-onset ( n =13) and late-onset ( n =16) PE were selected and compared with fetal growth restriction (FGR, n =26) or preterm birth (PTB, n =20) as controls, complications often occurring in PE, as well as with controls without PE, FGR or PTB ( n =36). Genome-wide methylation analysis (Illumina 450KA methylation array) was performed at 936 CpGs of 38 circadian clock-related genes in umbilical cord white blood cells (UCWBC), endothelial cells (HUVEC) and placental tissue. For statistical analysis a pathway approach was used and ANCOVA was applied with adjustment for gestational age at sampling. Bonferroni adjustment was used for multiple comparisons. Results DNA methylation differed between early-onset PE and PTB at 5 circadian clock-related CpGs in placental tissue \( 10 - 4 P ⩽ . 01 \) and at 22 CpGs in UCWBC \( 10 - 6 P ⩽ . 05 \) . The same comparison with controls revealed differences at 2 CpGs (P \( 10 - 4 P ⩽ . 05 \) . Moreover, in early-onset PE compared with FGR differences at 4 CpGs in UCWBC \( 10 - 4 P ⩽ . 03 \) were observed. Late-onset PE showed no differences between groups and tissues. Conclusion Here we show variations in epigenetic programming of the circadian clock pathway in early-onset PE only. Differences in placental and UCWB programming of circadian clock genes of interest and severity of PE are suggested. Future research should address whether these tissue specific epigenetic profiles can be used as early predictors of short and long term health.