Epigenetic changes of hepatic glucocorticoid receptor in sheep male offspring undernourished in utero
Stella Chadio A E , Basiliki Kotsampasi B , Stylliani Taka C , Emmanouil Liandris A , Nikolaos Papadopoulos C D and Elias Plakokefalos A
+ Author Affiliations
- Author Affiliations
A Department of Anatomy and Physiology of Farm Animals, Faculty of Animal Science and Aquaculture, Agricultural University of Athens, 75 Iera Odos, PO Box 11855, Athens, Greece.
B Research Institute of Animal Science, Directorate General of Agricultural Research, Hellenic Agricultural Organisation ‘DEMETER’, Paralimni, PO Box 58100, Giannitsa, Greece.
C Allergy Department, Second Paediatric Clinic, University of Athens, 41 Fidippidou, PO Box 11527, Athens, Greece.
D Centre for Paediatrics and Child Health, Institute of Human Development, University of Manchester, Royal Manchester Children’s Hospital, Manchester, M13 9WL, UK.
E Corresponding author. Email: shad@aua.gr
Reproduction, Fertility and Development 29(10) 1995-2004 https://doi.org/10.1071/RD16276
Submitted: 13 July 2016 Accepted: 1 December 2016 Published: 12 January 2017
Abstract
The aim of this study was to characterise the effects of maternal undernutrition during gestation on hepatic gluconeogenic enzyme gene expression and to determine whether such effects are mediated through epigenetic changes in the glucocorticoid receptor (GR). Pregnant ewes were fed a 50% nutrient-restricted diet from Day 0 to 30 (R1) or from Day 31 to 100 of gestation (R2) or a 100% diet throughout gestation (Control). After parturition lambs were fed to appetite. At 10 months of age offspring were euthanised and livers were removed. Maternal undernutrition did not affect offspring bodyweight at birth or at 10 months of age. However, liver weight of males of the R2 group was lower (P < 0.05) in relation to other groups. A significant (P < 0.05) hypomethylation of the hepatic GR promoter was revealed in males of the R2 group and a tendency towards the same in the R1 group, along with increased (P < 0.001) GR gene expression in both restricted groups. A significant increase (P < 0.05) in hepatic phosphoenolpyruvate carboxykinase (PEPCK) gene expression was found in male lambs of both undernourished groups, accompanied by increased (P < 0.01) protein levels, while no differences were detected for glucose-6-phosphatase (G6Pase) mRNA abundance and protein levels. In female lambs, no differences between groups were observed for any parameter studied. These data represent potential mechanisms by which insults in early life may lead to persistent physiological changes in the offspring.
Additional keywords: gluconeogenic genes, lamb, maternal undernutrition, methylation.
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