title: Maternal diets trigger sex-specific divergent trajectories of gene expression and epigenetic systems in mouse placenta.
abstract: Males and females responses to gestational overnutrition set the stage for subsequent sex-specific differences in adult onset non communicable diseases. Placenta, as a widely recognized programming agent, contibutes to the underlying processes. According to our previous findings, a high-fat diet during gestation triggers sex-specific epigenetic alterations within CpG and throughout the genome, together with the deregulation of clusters of imprinted genes. We further investigated the impact of diet and sex on placental histology, transcriptomic and epigenetic signatures in mice. Both basal gene expression and response to maternal high-fat diet were sexually dimorphic in whole placentas. Numerous genes showed sexually dimorphic expression, but only 11 genes regardless of the diet. In line with the key role of genes belonging to the sex chromosomes, 3 of these genes were Y-specific and 3 were X-specific. Amongst all the genes that were differentially expressed under a high-fat diet, only 16 genes were consistently affected in both males and females. The differences were not only quantitative but remarkably qualitative. The biological functions and networks of genes dysregulated differed markedly between the sexes. Seven genes of the epigenetic machinery were dysregulated, due to effects of diet, sex or both, including the Y- and X-linked histone demethylase paralogues Kdm5c and Kdm5d, which could mark differently male and female epigenomes. The DNA methyltransferase cofactor Dnmt3l gene expression was affected, reminiscent of our previous observation of changes in global DNA methylation. Overall, this striking sexual dimorphism of programming trajectories impose a considerable revision of the current dietary interventions protocols.
authors.affiliation: INRA, UMR1198 Biologie du Développement et Reproduction, Jouy-en-Josas, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Gabory
authors.forename: Laure
authors.initials: L
authors.lastname: Ferry
authors.forename: Isabelle
authors.initials: I
authors.lastname: Fajardy
authors.forename: Luc
authors.initials: L
authors.lastname: Jouneau
authors.forename: Jean-David
authors.initials: JD
authors.lastname: Gothié
authors.forename: Alexandre
authors.initials: A
authors.lastname: Vigé
authors.forename: Cécile
authors.initials: C
authors.lastname: Fleur
authors.forename: Sylvain
authors.initials: S
authors.lastname: Mayeur
authors.forename: Catherine
authors.initials: C
authors.lastname: Gallou-Kabani
authors.forename: Marie-Sylvie
authors.initials: MS
authors.lastname: Gross
authors.forename: Linda
authors.initials: L
authors.lastname: Attig
authors.forename: Anne
authors.initials: A
authors.lastname: Vambergue
authors.forename: Jean
authors.initials: J
authors.lastname: Lesage
authors.forename: Brigitte
authors.initials: B
authors.lastname: Reusens
authors.forename: Didier
authors.initials: D
authors.lastname: Vieau
authors.forename: Claude
authors.initials: C
authors.lastname: Remacle
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Jais
authors.forename: Claudine
authors.initials: C
authors.lastname: Junien
mesh_terms: D000818:Animals; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D044127:Epigenesis, Genetic; D005260:Female; D015870:Gene Expression; D015971:Gene Expression Regulation, Enzymologic; D056466:Histone Demethylases; D008297:Male; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics / Q000378:metabolism; D010920:Placenta / Q000378:metabolism* / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics* / Q000378:metabolism; D039401:Prenatal Nutritional Physiological Phenomena; D012727:Sex Characteristics; D059467:Transcriptome
chemical_list: D056466:Histone Demethylases; C490173:Kdm5c protein, mouse; D010089:Oxidoreductases, N-Demethylating; C498796:Dnmt3l protein, mouse; D004248:DNA (Cytosine-5-)-Methyltransferases