Paediatrics Publications
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.