Increased epigenetic alterations at the promoters of transcriptional regulators following inadequate maternal gestational weight gain

Sci Rep. 2015 Sep 29;5:14224. doi: 10.1038/srep14224.

Abstract

Epigenetic modifications are thought to serve as a memory of exposure to in utero environments. However, few human studies have investigated the associations between maternal nutritional conditions during pregnancy and epigenetic alterations in offspring. In this study, we report genome-wide methylation profiles for 33 postpartum placentas from pregnancies of normal and foetal growth restriction with various extents of maternal gestational weight gain. Epigenetic alterations accumulate in the placenta under adverse in utero environments, as shown by application of Smirnov-Grubbs' outlier test. Moreover, hypermethylation occurs frequently at the promoter regions of transcriptional regulator genes, including polycomb targets and zinc-finger genes, as shown by annotations of the genomic and functional features of loci with altered DNA methylation. Aberrant epigenetic modifications at such developmental regulator loci, if occurring in foetuses as well, will elevate the risk of developing various diseases, including metabolic and mental disorders, later in life.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Birth Weight
  • Case-Control Studies
  • CpG Islands
  • DNA Methylation
  • Epigenesis, Genetic*
  • Female
  • Fetal Growth Retardation / genetics*
  • Fetal Growth Retardation / pathology
  • Fetus
  • Forkhead Box Protein L2
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Gene Ontology
  • Genetic Loci
  • Genome-Wide Association Study
  • Gestational Age
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Molecular Sequence Annotation
  • Placenta / metabolism*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / genetics*
  • Prenatal Exposure Delayed Effects / pathology
  • Promoter Regions, Genetic*
  • Weight Gain / genetics*

Substances

  • FOXC1 protein, human
  • FOXL2 protein, human
  • Forkhead Box Protein L2
  • Forkhead Transcription Factors
  • HOXB7 protein, human
  • Homeodomain Proteins