Epigenetic modification of the pentose phosphate pathway and the IGF-axis in women with gestational diabetes mellitus

Epigenomics. 2019 Sep;11(12):1371-1385. doi: 10.2217/epi-2018-0206. Epub 2019 Oct 4.

Abstract

Aim: Gestational diabetes mellitus (GDM) has been linked with adverse long-term health outcomes for the fetus and mother. These effects may be mediated by epigenetic modifications. Materials & methods: Genome-wide RNA sequencing was performed in placental tissue and maternal blood in six GDM and six non-GDM pregnancies. Promoter region DNA methylation was examined for selected genes and correlated with gene expression to examine an epigenetic modulator mechanism. Results: Reductions of mRNA expression and increases in promoter methylation were observed for G6PD in GDM women, and for genes encoding IGF-binding proteins in GDM-exposed placenta. Conclusion: GDM involves epigenetic attenuation of G6PD, which may lead to hyperglycemia and oxidative stress, and the IGF-axis, which may modulate fetal macrosomia.

Keywords: DNA methylation; IGF binding protein; RNA sequencing; epigenetics; gestational diabetes mellitus; glucose-6-phosphate dehydrogenase; pentose phosphate pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Methylation*
  • Diabetes, Gestational / genetics*
  • Down-Regulation
  • Epigenesis, Genetic
  • Female
  • Gene Expression Profiling
  • Gestational Age
  • Glucosephosphate Dehydrogenase / genetics*
  • Humans
  • Infant, Newborn
  • Insulin-Like Growth Factor Binding Proteins / genetics*
  • Pentose Phosphate Pathway
  • Pregnancy
  • Sequence Analysis, RNA

Substances

  • Insulin-Like Growth Factor Binding Proteins
  • G6PD protein, human
  • Glucosephosphate Dehydrogenase