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

Emilie M. Herzog, Alex J. Eggink, Sten P. Willemsen, Roderick C. Slieker, Kim P.J. Wijnands, Janine F. Felix, Jun Chen, Andrew Stubbs, Peter J. van der Spek, Joyce B. van Meurs, Régine P.M. Steegers-Theunissen

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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 might elucidate the increased cardiovascular- and metabolic disease susceptibility in PE offspring. Methods A nested case-control study was conducted in The Rotterdam Periconceptional Cohort 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, newborn umbilical cord white blood cells (UC-WBC) and umbilical vein endothelial cells 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 tissue-specific analysis between EOPE and PTB controls revealed 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-metabolic developmental pathways. Discussion 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.

Original languageEnglish (US)
Pages (from-to)122-132
Number of pages11
JournalPlacenta
Volume58
DOIs
StatePublished - Oct 1 2017
Externally publishedYes

Fingerprint

Pre-Eclampsia
Placenta
Premature Birth
Fetal Blood
Leukocytes
Cardiovascular Diseases
Metabolic Diseases
Epigenomics
Pregnancy
Linear Models
Placentation
Umbilical Veins
Disease Susceptibility
DNA Methylation
Fetal Development
Cardiovascular System
Metabolic Networks and Pathways
Contraception
Methylation
Case-Control Studies

Keywords

  • Cardiovascular disease
  • DNA methylation
  • Fetal programming
  • HUVEC
  • Illumina HumanMethylation450K BeadChip
  • Umbilical cord white blood cells

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology
  • Developmental Biology

Cite this

Herzog, E. M., Eggink, A. J., Willemsen, S. P., Slieker, R. C., Wijnands, K. P. J., Felix, J. F., ... Steegers-Theunissen, R. P. M. (2017). Early- and late-onset preeclampsia and the tissue-specific epigenome of the placenta and newborn. Placenta, 58, 122-132. https://doi.org/10.1016/j.placenta.2017.08.070

Early- and late-onset preeclampsia and the tissue-specific epigenome of the placenta and newborn. / Herzog, Emilie M.; Eggink, Alex J.; Willemsen, Sten P.; Slieker, Roderick C.; Wijnands, Kim P.J.; Felix, Janine F.; Chen, Jun; Stubbs, Andrew; van der Spek, Peter J.; van Meurs, Joyce B.; Steegers-Theunissen, Régine P.M.

In: Placenta, Vol. 58, 01.10.2017, p. 122-132.

Research output: Contribution to journalArticle

Herzog, EM, Eggink, AJ, Willemsen, SP, Slieker, RC, Wijnands, KPJ, Felix, JF, Chen, J, Stubbs, A, van der Spek, PJ, van Meurs, JB & Steegers-Theunissen, RPM 2017, 'Early- and late-onset preeclampsia and the tissue-specific epigenome of the placenta and newborn', Placenta, vol. 58, pp. 122-132. https://doi.org/10.1016/j.placenta.2017.08.070
Herzog EM, Eggink AJ, Willemsen SP, Slieker RC, Wijnands KPJ, Felix JF et al. Early- and late-onset preeclampsia and the tissue-specific epigenome of the placenta and newborn. Placenta. 2017 Oct 1;58:122-132. https://doi.org/10.1016/j.placenta.2017.08.070
Herzog, Emilie M. ; Eggink, Alex J. ; Willemsen, Sten P. ; Slieker, Roderick C. ; Wijnands, Kim P.J. ; Felix, Janine F. ; Chen, Jun ; Stubbs, Andrew ; van der Spek, Peter J. ; van Meurs, Joyce B. ; Steegers-Theunissen, Régine P.M. / Early- and late-onset preeclampsia and the tissue-specific epigenome of the placenta and newborn. In: Placenta. 2017 ; Vol. 58. pp. 122-132.
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AU - Felix, Janine F.

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