DNA Methylation and Expression Patterns of Selected Genes in First-Trimester Placental Tissue from Pregnancies with Small-for-Gestational-Age Infants at Birth

Biol Reprod. 2016 Feb;94(2):37. doi: 10.1095/biolreprod.115.131698. Epub 2016 Jan 6.


Variations in DNA methylation levels in the placenta are thought to influence gene expression and are associated with complications of pregnancy, like fetal growth restriction (FGR). The most important cause for FGR is placental dysfunction. Here, we examined whether changes in DNA methylation, followed by gene expression changes, are mechanistically involved in the etiology of FGR. In this retrospective case-control study, we examined the association between small-for-gestational-age (SGA) children and both DNA methylation and gene expression levels of the genes WNT2, IGF2/H19, SERPINA3, HERVWE1, and PPARG in first-trimester placental tissue. We also examined the repetitive element LINE-1. These candidate genes have been reported in the literature to be associated with SGA. We used first-trimester placental tissue from chorionic villus biopsies. A total of 35 SGA children (with a birth weight below the 10th percentile) were matched to 70 controls based on their gestational age. DNA methylation levels were analyzed by pyrosequencing and mRNA levels were analyzed by real-time PCR. None of the average DNA methylation levels, measured for each gene, showed a significant difference between SGA placental tissue compared to control tissue. However, hypermethylation of WNT2 was detected on two CpG positions in SGA. This was not associated with changes in gene expression. Apart from two CpG positions of the WNT2 gene, in early placenta samples, no evident changes in DNA methylation or expression were found. This indicates that the already reported changes in term placenta are not present in the early placenta, and therefore must arise after the first trimester.

Keywords: FGR; IUGR; SGA; epigenetics; methylation; placenta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • DNA Methylation*
  • Female
  • Fetal Growth Retardation / genetics
  • Fetal Growth Retardation / metabolism*
  • Humans
  • Infant, Newborn
  • Infant, Small for Gestational Age
  • Insulin-Like Growth Factor II / genetics
  • Insulin-Like Growth Factor II / metabolism
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Placenta / metabolism*
  • Pregnancy
  • Pregnancy Trimester, First / genetics
  • Pregnancy Trimester, First / metabolism*
  • Retrospective Studies
  • Serpins / genetics
  • Serpins / metabolism
  • Wnt2 Protein / genetics
  • Wnt2 Protein / metabolism


  • IGF2 protein, human
  • PPAR gamma
  • SERPINA3 protein, human
  • Serpins
  • Wnt2 Protein
  • Insulin-Like Growth Factor II