Maternal pregravid obesity changes gene expression profiles toward greater inflammation and reduced insulin sensitivity in umbilical cord

Pediatr Res. 2014 Aug;76(2):202-10. doi: 10.1038/pr.2014.72. Epub 2014 May 12.

Abstract

Background: Maternal obesity is associated with unfavorable outcomes, which may be reflected in the as yet undiscovered gene expression profiles of the umbilical cord (UC).

Methods: UCs from 12 lean (pregravid BMI < 24.9) and 10 overweight/obese (pregravid BMI ≥ 25) women without gestational diabetes were collected for gene expression analysis using Human Primeview microarrays. Metabolic parameters were assayed in mother's plasma and cord blood.

Results: Although offspring birth weight and adiposity (at 2 wk) did not differ between groups, expression of 232 transcripts was affected in UC from overweight/obese compared with those of lean mothers. Gene-set enrichment analysis revealed an upregulation of genes related to metabolism, stimulus and defense response, and inhibitory to insulin signaling in the overweight/obese group. We confirmed that EGR1, periostin, and FOSB mRNA expression was induced in UCs from overweight/obese mothers, while endothelin receptor B, KLF10, PEG3, and EGLN3 expression was decreased. Messenger RNA expression of EGR1, FOSB, MEST, and SOCS1 were positively correlated (P < 0.05) with mother's first-trimester body fat mass (%).

Conclusion: Our data suggest a positive association between maternal obesity and changes in UC gene expression profiles favoring inflammation and insulin resistance, potentially predisposing infants to develop metabolic dysfunction later on in life.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adiposity / physiology
  • Adult
  • Analysis of Variance
  • Anthropometry
  • Blotting, Western
  • Cell Adhesion Molecules / metabolism
  • DNA Primers / genetics
  • Early Growth Response Protein 1 / metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation / physiology*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Inflammation / physiopathology*
  • Insulin / blood
  • Insulin Resistance / physiology*
  • Leptin / blood
  • Maternal Nutritional Physiological Phenomena / physiology*
  • Microarray Analysis
  • Obesity / physiopathology*
  • Proto-Oncogene Proteins c-fos / metabolism
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Umbilical Cord / metabolism
  • Umbilical Cord / physiopathology*

Substances

  • Cell Adhesion Molecules
  • DNA Primers
  • EGR1 protein, human
  • Early Growth Response Protein 1
  • FOSB protein, human
  • Insulin
  • Leptin
  • POSTN protein, human
  • Proto-Oncogene Proteins c-fos