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Dichotomy in the Impact of Elevated Maternal Glucose Levels on Neonatal Epigenome

Ives Yubin Lim1,2,3, Xinyi Lin1,4,5, Ai Ling Teh1

  • 1Singapore Institute for Clinical Sciences (SICS), A*STAR, 117609, Singapore.

The Journal of Clinical Endocrinology and Metabolism
|October 11, 2021
PubMed

Insights

Maternal glucose levels during pregnancy impact offspring epigenome differently. Elevated 2-hour glucose (2hPG) is linked to global hypomethylation in newborns, suggesting distinct gestational diabetes pathologies.

Area of Science:

  • Reproductive biology
  • Epigenetics
  • Metabolic health

Background:

  • Antenatal hyperglycemia increases risks for mothers and children.
  • Offspring epigenome variations can reflect in utero glycemic exposure.
  • Epigenetic changes may lead to distinct long-term health consequences for children.

Purpose of the Study:

  • To investigate differences in associations between maternal glucose status and offspring cord tissue DNA methylation.
  • To examine how basal glucose and glucose handling during pregnancy relate to clinical factors and fetal epigenome.

Main Methods:

  • Study included 830 mother-offspring dyads from the 'Growing Up in Singapore Towards Healthy Outcomes' cohort.
  • Offspring epigenome profiled using Illumina HumanMethylation450 arrays on umbilical cord tissue.
  • Associations of maternal fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPG) with maternal phenotypes and offspring epigenome were analyzed.

Main Results:

  • Maternal age, BMI, and blood pressure correlated with both FPG and 2hPG.
  • Ethnicity, height, weight gain, alcohol, and tobacco use showed differential associations with FPG vs. 2hPG.
  • Elevated 2hPG in mothers was associated with global hypomethylation in offspring epigenome; CpG sites and gene ontologies differed between FPG and 2hPG.

Conclusions:

  • Two common glycemic indices for gestational diabetes diagnosis may indicate different pathophysiological processes.
  • These distinct glycemic measures appear to have differential impacts on the offspring's DNA methylome.
  • Findings highlight the importance of specific glycemic profiles in pregnancy for fetal epigenetic programming.
Abstract

Keywords:
2h oral glucose tolerance testDNA methylationepigenome wide association studyfasting plasma glucosegestational diabetes

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