title: Metabolic programming of MEST DNA methylation by intrauterine exposure to gestational diabetes mellitus.
abstract: Epigenetic processes are primary candidates when searching for mechanisms that can stably modulate gene expression and metabolic pathways according to early life conditions. To test the effects of gestational diabetes mellitus (GDM) on the epigenome of the next generation, cord blood and placenta tissue were obtained from 88 newborns of mothers with dietetically treated GDM, 98 with insulin-dependent GDM, and 65 without GDM. Bisulfite pyrosequencing was used to compare the methylation levels of seven imprinted genes involved in prenatal and postnatal growth, four genes involved in energy metabolism, one anti-inflammatory gene, one tumor suppressor gene, one pluripotency gene, and two repetitive DNA families. The maternally imprinted MEST gene, the nonimprinted glucocorticoid receptor NR3C1 gene, and interspersed ALU repeats showed significantly decreased methylation levels (4-7 percentage points for MEST, 1-2 for NR3C1, and one for ALUs) in both GDM groups, compared with controls, in both analyzed tissues. Significantly decreased blood MEST methylation (3 percentage points) also was observed in adults with morbid obesity compared with normal-weight controls. Our results support the idea that intrauterine exposure to GDM has long-lasting effects on the epigenome of the offspring. Specifically, epigenetic malprogramming of MEST may contribute to obesity predisposition throughout life.
authors.affiliation: Institute of Human Genetics, Julius Maximilians University, Würzburg, Germany.
authors.forename: Nady
authors.initials: N
authors.lastname: El Hajj
authors.forename: Galyna
authors.initials: G
authors.lastname: Pliushch
authors.forename: Eberhard
authors.initials: E
authors.lastname: Schneider
authors.forename: Marcus
authors.initials: M
authors.lastname: Dittrich
authors.forename: Tobias
authors.initials: T
authors.lastname: Müller
authors.forename: Michael
authors.initials: M
authors.lastname: Korenkov
authors.forename: Melanie
authors.initials: M
authors.lastname: Aretz
authors.forename: Ulrich
authors.initials: U
authors.lastname: Zechner
authors.forename: Harald
authors.initials: H
authors.lastname: Lehnen
authors.forename: Thomas
authors.initials: T
authors.lastname: Haaf
mesh_terms: D000328:Adult; D019175:DNA Methylation / Q000502:physiology*; D016640:Diabetes, Gestational / Q000178:diet therapy / Q000188:drug therapy / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000502:physiology*; D005260:Female; D005312:Fetal Blood; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007231:Infant, Newborn; D007328:Insulin / Q000627:therapeutic use; D005810:Multigene Family; D009765:Obesity / Q000235:genetics*; D010920:Placenta; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011506:Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D007328:Insulin; D011506:Proteins; C103637:mesoderm specific transcript protein