title: Hepatic IGF1 DNA methylation is influenced by gender but not by intrauterine growth restriction in the young lamb.
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 (MF (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.
authors: 1Rowett Institute of Nutrition and Health,University of Aberdeen,Aberdeen,UK.
authors: D J
authors: http://orcid.org/0000-0002-5421-5395
authors: DJ
authors: Carr
authors: 1Rowett Institute of Nutrition and Health,University of Aberdeen,Aberdeen,UK.
authors: J S
authors: JS
authors: Milne
authors: 1Rowett Institute of Nutrition and Health,University of Aberdeen,Aberdeen,UK.
authors: R P
authors: RP
authors: Aitken
authors: 1Rowett Institute of Nutrition and Health,University of Aberdeen,Aberdeen,UK.
authors: C L
authors: CL
authors: Adam
authors: 1Rowett Institute of Nutrition and Health,University of Aberdeen,Aberdeen,UK.
authors: J M
authors: JM
authors: Wallace
mesh_terms: D000818:Animals; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D010920:Placenta / Q000098:blood supply; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D012756:Sheep / Q000196:embryology / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I
keywords: IGF1; IUGR; epigenetics; methylation; sheep