title: Sex- and diet-specific changes of imprinted gene expression and DNA methylation in mouse placenta under a high-fat diet.
abstract: BACKGROUND
  Changes in imprinted gene dosage in the placenta may compromise the prenatal control of nutritional resources. Indeed monoallelic behaviour and sensitivity to changes in regional epigenetic state render imprinted genes both vulnerable and adaptable.
  
  
  RESULTS
  We investigated whether a high-fat diet (HFD) during pregnancy modified the expression of imprinted genes and local and global DNA methylation patterns in the placenta. Pregnant mice were fed a HFD or a control diet (CD) during the first 15 days of gestation. We compared gene expression patterns in total placenta homogenates, for male and female offspring, by the RT-qPCR analysis of 20 imprinted genes. Sexual dimorphism and sensitivity to diet were observed for nine genes from four clusters on chromosomes 6, 7, 12 and 17. As assessed by in situ hybridization, these changes were not due to variation in the proportions of the placental layers. Bisulphite-sequencing analysis of 30 CpGs within the differentially methylated region (DMR) of the chromosome 17 cluster revealed sex- and diet-specific differential methylation of individual CpGs in two conspicuous subregions. Bioinformatic analysis suggested that these differentially methylated CpGs might lie within recognition elements or binding sites for transcription factors or factors involved in chromatin remodelling. Placental global DNA methylation, as assessed by the LUMA technique, was also sexually dimorphic on the CD, with lower methylation levels in male than in female placentae. The HFD led to global DNA hypomethylation only in female placenta. Bisulphite pyrosequencing showed that neither B1 nor LINE repetitive elements could account for these differences in DNA methylation.
  
  
  CONCLUSIONS
  A HFD during gestation triggers sex-specific epigenetic alterations within CpG and throughout the genome, together with the deregulation of clusters of imprinted genes important in the control of many cellular, metabolic and physiological functions potentially involved in adaptation and/or evolution. These findings highlight the importance of studying both sexes in epidemiological protocols and dietary interventions.
authors.affiliation: Inserm, AP-HP, Université Paris-Descartes, Faculté de Médecine, Hôpital Necker-Enfants Malades, U781, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Gallou-Kabani
authors.forename: Anne
authors.initials: A
authors.lastname: Gabory
authors.forename: Jörg
authors.initials: J
authors.lastname: Tost
authors.forename: Mohsen
authors.initials: M
authors.lastname: Karimi
authors.forename: Sylvain
authors.initials: S
authors.lastname: Mayeur
authors.forename: Jean
authors.initials: J
authors.lastname: Lesage
authors.forename: Elsa
authors.initials: E
authors.lastname: Boudadi
authors.forename: Marie-Sylvie
authors.initials: MS
authors.lastname: Gross
authors.forename: Julien
authors.initials: J
authors.lastname: Taurelle
authors.forename: Alexandre
authors.initials: A
authors.lastname: Vigé
authors.forename: Christophe
authors.initials: C
authors.lastname: Breton
authors.forename: Brigitte
authors.initials: B
authors.lastname: Reusens
authors.forename: Claude
authors.initials: C
authors.lastname: Remacle
authors.forename: Didier
authors.initials: D
authors.lastname: Vieau
authors.forename: Tomas J
authors.initials: TJ
authors.lastname: Ekström
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Jais
authors.forename: Claudine
authors.initials: C
authors.lastname: Junien
mesh_terms: D000483:Alleles; D000821:Animal Feed; D000818:Animals; D019175:DNA Methylation; D004041:Dietary Fats / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005260:Female; D018628:Gene Dosage; D005786:Gene Expression Regulation; D018392:Genomic Imprinting; D008297:Male; D051379:Mice; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal; D012737:Sex Factors
chemical_list: D004041:Dietary Fats