Document Detail

Epigenetic changes in fetal hypothalamic energy regulating pathways are associated with maternal undernutrition and twinning.
MedLine Citation:
PMID:  22223754     Owner:  NLM     Status:  MEDLINE    
Undernutrition during pregnancy is implicated in the programming of offspring for the development of obesity and diabetes. We hypothesized that maternal programming causes epigenetic changes in fetal hypothalamic pathways regulating metabolism. This study used sheep to examine the effect of moderate maternal undernutrition (60 d before to 30 d after mating) and twinning to investigate changes in the key metabolic regulators proopiomelanocortin (POMC) and the glucocorticoid receptor (GR) in fetal hypothalami. Methylation of the fetal hypothalamic POMC promoter was reduced in underfed singleton, fed twin, and underfed twin groups (60, 73, and 63% decrease, respectively). This was associated with reduced DNA methyltransferase activity and altered histone methylation and acetylation. Methylation of the hypothalamic GR promoter was decreased in both twin groups and in maternally underfed singleton fetuses (52, 65, and 55% decrease, respectively). This correlated with changes in histone methylation and acetylation and increased GR mRNA expression in the maternally underfed singleton group. Alterations in GR were hypothalamic specific, with no changes in hippocampi. Unaltered levels of OCT4 promoter methylation indicated gene-specific effects. In conclusion, twinning and periconceptional undernutrition are associated with epigenetic changes in fetal hypothalamic POMC and GR genes, potentially resulting in altered energy balance regulation in the offspring.
Ghazala Begum; Adam Stevens; Emma Bolton Smith; Kristin Connor; John R G Challis; Frank Bloomfield; Anne White
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-01-05
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  26     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-02     Completed Date:  2012-05-31     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1694-703     Citation Subset:  IM    
Department of Endocrinology and Diabetes, University of Manchester, Manchester, UK.
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MeSH Terms
DNA Methylation
Energy Metabolism*
Epigenesis, Genetic*
Fetus / anatomy & histology,  physiology*
Gene Expression Regulation, Developmental
Hypothalamus / physiology*
Malnutrition / genetics*
Maternal Nutritional Physiological Phenomena*
Pregnancy Complications / genetics,  metabolism
Pro-Opiomelanocortin / genetics,  metabolism
Promoter Regions, Genetic
Random Allocation
Receptors, Glucocorticoid / genetics,  metabolism
Twins / genetics*
Grant Support
//Canadian Institutes of Health Research
Reg. No./Substance:
0/Receptors, Glucocorticoid; 66796-54-1/Pro-Opiomelanocortin

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