Intrauterine Hyperglycemia Is Associated with an Impaired Postnatal Response to Oxidative Damage

Jessica N. Tozour, Fabien Delahaye, Masako Suzuki, Aaron Praiss, Yongmei Zhao, Lingguang Cai, Hye J. Heo, John M. Greally, Francine Hughes

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Hyperglycemia and other adverse exposures early in life that reprogram stem cells may lead to long-lasting phenotypic influences over the lifetime of an individual. Hyperglycemia and oxidative stress cause DNA damage when they exceed the protective capabilities of the cell, in turn affecting cellular function. DNA damage in response to hyperglycemia and oxidative stress was studied in human umbilical cord mesenchymal stem cells (hUC-MSCs) from large-for-gestational-age (LGA) infants of mothers with gestational diabetes mellitus (LGA-GDM) and control subjects. We tested the response of these cells to hyperglycemia and oxidative stress, measuring reactive oxygen species (ROS) levels and antioxidant enzyme activities. We find that hUC-MSCs from LGA-GDM infants have increased DNA damage when exposed to oxidative stress. With the addition of hyperglycemic conditions, these cells have an increase in ROS and a decrease in antioxidant glutathione peroxidase (GPx) activity, indicating a mechanism for the increased ROS and DNA damage. This study demonstrates that a memory of in utero hyperglycemia, mediated through downregulation of GPx activity, leads to an increased susceptibility to oxidative stress. The alteration of GPx function in self-renewing stem cells, can mediate the effect of intrauterine hyperglycemia to be propagated into adulthood and contribute to disease susceptibility.

Original languageEnglish (US)
Pages (from-to)683-691
Number of pages9
JournalStem Cells and Development
Volume27
Issue number10
DOIs
StatePublished - May 15 2018

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Keywords

  • DNA damage
  • gestational diabetes
  • glutathione peroxidase
  • mesenchymal stem cells
  • oxidative stress

ASJC Scopus subject areas

  • Hematology
  • Developmental Biology
  • Cell Biology

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