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Hepatic IGF1 DNA methylation is influenced by gender but not by intrauterine growth restriction in the young lamb

Published online by Cambridge University Press:  27 August 2015

D. J. Carr Open the ORCID record for D. J. Carr [Opens in a new window] ,
J. S. Milne ,
R. P. Aitken ,
C. L. Adam  and
J. M. Wallace
D. J. Carr*
Affiliation:
Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, UK UCL Institute for Women’s Health, University College London, London, UK
J. S. Milne
Affiliation:
Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, UK
R. P. Aitken
Affiliation:
Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, UK
C. L. Adam
Affiliation:
Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, UK
J. M. Wallace
Affiliation:
Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, UK
*
*Address for correspondence: Dr D. J. Carr, Prenatal Cell and Gene Therapy Group, UCL Institute for Women’s Health, University College London, 86-96 Chenies Mews, London WC1E 6HX, UK. (Email davidcarr@doctors.org.uk)
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Abstract

Intrauterine growth restriction (IUGR) and postnatal catch-up growth confer an increased risk of adult-onset disease. Overnourishment of adolescent ewes generates IUGR in ∼50% of lambs, which subsequently exhibit increased fractional growth rates. We investigated putative epigenetic changes underlying this early postnatal phenotype by quantifying gene-specific methylation at cytosine:guanine (CpG) dinucleotides. Hepatic DNA/RNA was extracted from IUGR [eight male (M)/nine female (F)] and normal birth weight (12 M/9 F) lambs. Polymerase chain reaction was performed using primers targeting CpG islands in 10 genes: insulin, growth hormone, insulin-like growth factor (IGF)1, IGF2, H19, insulin receptor, growth hormone receptor, IGF receptors 1 and 2, and the glucocorticoid receptor. Using pyrosequencing, methylation status was determined by quantifying cytosine:thymine ratios at 57 CpG sites. Messenger RNA (mRNA) expression of IGF system genes and plasma IGF1/insulin were determined. DNA methylation was independent of IUGR status but sexual dimorphism in IGF1 methylation was evident (M<F, P=0.008). IGF1 mRNA:18S and plasma IGF1 were M>F (both P<0.001). IGF1 mRNA expression correlated negatively with IGF1 methylation (r=−0.507, P=0.002) and positively with plasma IGF1 (r=0.884, P<0.001). Carcass and empty body weights were greater in males (P=0.002–0.014) and this gender difference in early body conformation was mirrored by sexual dimorphism in hepatic IGF1 DNA methylation, mRNA expression and plasma IGF1 concentrations.

Keywords

epigeneticsIGF1IUGRmethylationsheep
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 6 , Supplement 6 , December 2015 , pp. 558 - 572
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Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2015 

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