Enhanced trimethylation of histone H3 mediates impaired expression of hepatic glucose 6-phosphatase expression in offspring from rat dams exposed to hypoxia during pregnancy

Authors

Jessica E. Osumek, Western University
Andrew Revesz, Western University
Jude S. Morton, University of Alberta
Sandra T. Davidge, University of Alberta
Daniel B. Hardy, Western UniversityFollow

Document Type

Article

Publication Date

1-1-2014

Journal

Reproductive Sciences

Volume

21

Issue

1

First Page

112

Last Page

121

URL with Digital Object Identifier

10.1177/1933719113492212

Abstract

Given that hepatic glucose 6-phosphatase (G6Pase, involved in gluconeogenesis) has been demonstrated to be altered long term in animal models of intrauterine growth restriction (IUGR), we hypothesized that hypoxia in utero may regulate G6Pase expression via epigenetic mechanisms. To address this further, a rat model of maternal hypoxia leading to IUGR and impaired liver growth was utilized. In the 12-month-old male offspring of pregnant rat dams exposed to 11.5% atmospheric oxygen from gestational day (gd) 15 to gd 21, nonfasting glucose was lower in association with decreased hepatic G6Pase messenger RNA and protein levels. This was concomitant with enhanced methylation of histone H3 [K9] surrounding the promoter of G6Pase. Moreover, when McA-RH7777 hepatoma cells were exposed to various concentrations of oxygen for 48 hours, we observed an oxygen-dependent decrease in G6Pase expression associated with enhanced histone H3 [K9] methylation. Collectively, these results indicate that hypoxia directly and indirectly impairs G6Pase expression through enhanced methylation of histone H3 [K9]. © The Author(s) 2013.