title: Identifying placental epigenetic alterations in an intrauterine growth restriction (IUGR) rat model induced by gestational protein deficiency.
abstract: Poor maternal nutrition during gestation can lead to intrauterine growth retardation (IUGR), a main cause of low birth weight associated with high neonatal morbidity and mortality. Such early uterine environmental exposures can impact the neonatal epigenome to render later-in-life disease susceptibility. We established in Wistar Han rats a mild IUGR model induced by gestational protein deficiency (i.e. 9% crude protein in low protein diet vs. 21% in control, from GD 0 to 21) to identify alterations in gene expression and methylation patterns in certain genes implicated in human IUGR or in placental development. We found differential gene expression of Wnt2 and Dlk1 between IUGR and control. Notably, Wnt2 exhibited significant decrease while Dlk1 increase in IUGR placentas, correlating to decrease in fetal and placental weight. Methylation patterns encompassing 30 CpGs in the Wnt2 promoter region revealed variability in both IUGR and control placentas, but a site-specific hypomethylation was evident in IUGR placentas. Our present findings further support a key role of maternal gestational nutrition in defining the neonatal epigenome.
authors.affiliation: Toxicology and Environmental Hygiene, Fraunhofer Institute for Toxicology and Experimental Medicine, Nikolai-Fuchs Strasse 1, 30625 Hannover, Germany. Electronic address: reamon-buettner@item.fraunhofer.de.
authors.forename: Stella Marie
authors.initials: SM
authors.lastname: Reamon-Buettner
authors.affiliation: Toxicology and Environmental Hygiene, Fraunhofer Institute for Toxicology and Experimental Medicine, Nikolai-Fuchs Strasse 1, 30625 Hannover, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Buschmann
authors.affiliation: Toxicology and Environmental Hygiene, Fraunhofer Institute for Toxicology and Experimental Medicine, Nikolai-Fuchs Strasse 1, 30625 Hannover, Germany.
authors.forename: Geertje
authors.initials: G
authors.lastname: Lewin
mesh_terms: D000818:Animals; D019175:DNA Methylation; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology* / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011488:Protein Deficiency / Q000150:complications* / Q000235:genetics; D017208:Rats, Wistar; D051154:Wnt2 Protein / Q000235:genetics
chemical_list: C512923:Dlk1 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051154:Wnt2 Protein
keywords: 5-Hydroxymethylcytosine (5-hmC); 5-Methylcytosine (5-mC); DNA methylation; Dlk1; Epigenetics; IUGR; Placenta; Wnt2