title: Expression of epigenetic machinery genes is sensitive to maternal obesity and weight loss in relation to fetal growth in mice.
abstract: BACKGROUND
  Maternal obesity impacts fetal growth and pregnancy outcomes. To counteract the deleterious effects of obesity on fertility and pregnancy issue, preconceptional weight loss is recommended to obese women. Whether this weight loss is beneficial/detrimental for offspring remains poorly explored. Epigenetic mechanisms could be affected by maternal weight changes, perturbing expression of key developmental genes in the placenta or fetus. Our aim was to investigate the effects of chronic maternal obesity on feto-placental growth along with the underlying epigenetic mechanisms. We also tested whether preconceptional weight loss could alleviate these effects.
  
  
  RESULTS
  Female mice were fed either a control diet (CTRL group), a high-fat diet (obese (OB) group), or a high-fat diet switched to a control diet 2 months before conception (weight loss (WL) group). At mating, OB females presented an obese phenotype while WL females normalized metabolic parameters. At embryonic day 18.5 (E18.5), fetuses from OB females presented fetal growth restriction (FGR; -13 %) and 28 % of the fetuses were small for gestational age (SGA). Fetuses from WL females normalized this phenotype. The expression of 60 epigenetic machinery genes and 32 metabolic genes was measured in the fetal liver, placental labyrinth, and junctional zone. We revealed 23 genes altered by maternal weight trajectories in at least one of three tissues. The fetal liver and placental labyrinth were more responsive to maternal obesity than junctional zone. One third (18/60) of the epigenetic machinery genes were differentially expressed between at least two maternal groups. Interestingly, genes involved in the histone acetylation pathway were particularly altered (13/18). In OB group, lysine acetyltransferases and Bromodomain-containing protein 2 were upregulated, while most histone deacetylases were downregulated. In WL group, the expression of only a subset of these genes was normalized.
  
  
  CONCLUSIONS
  This study highlights the high sensitivity of the epigenetic machinery gene expression, and particularly the histone acetylation pathway, to maternal obesity. These obesity-induced transcriptional changes could alter the placental and the hepatic epigenome, leading to FGR. Preconceptional weight loss appears beneficial to fetal growth, but some effects of previous obesity were retained in offspring phenotype.
authors.affiliation: UMR BDR, INRA, ENVA, Université Paris Saclay, 78350 Jouy en Josas, France ; Ecole Doctorale 394 "Physiologie, physiopathologie et thérapeutique", Université Pierre et Marie Curie, 75252 Paris, France.
authors.forename: Polina E
authors.initials: PE
authors.lastname: Panchenko
authors.affiliation: UMR BDR, INRA, ENVA, Université Paris Saclay, 78350 Jouy en Josas, France ; Ecole Doctorale 394 "Physiologie, physiopathologie et thérapeutique", Université Pierre et Marie Curie, 75252 Paris, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Voisin
authors.affiliation: UMR BDR, INRA, ENVA, Université Paris Saclay, 78350 Jouy en Josas, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Jouin
authors.affiliation: UMR BDR, INRA, ENVA, Université Paris Saclay, 78350 Jouy en Josas, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Jouneau
authors.affiliation: UMR BDR, INRA, ENVA, Université Paris Saclay, 78350 Jouy en Josas, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Prézelin
authors.affiliation: Univ. Lille, EA4489, Équipe Malnutrition Maternelle et Programmation des Maladies Métaboliques, F59000 Lille, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Lecoutre
authors.affiliation: Univ. Lille, EA4489, Équipe Malnutrition Maternelle et Programmation des Maladies Métaboliques, F59000 Lille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Breton
authors.affiliation: UMR BDR, INRA, ENVA, Université Paris Saclay, 78350 Jouy en Josas, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Jammes
authors.affiliation: UMR BDR, INRA, ENVA, Université Paris Saclay, 78350 Jouy en Josas, France ; Université Versailles Saint-Quentin en Yvelines (UVSQ), Guyancourt, France.
authors.forename: Claudine
authors.initials: C
authors.lastname: Junien
authors.affiliation: UMR BDR, INRA, ENVA, Université Paris Saclay, 78350 Jouy en Josas, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Gabory
mesh_terms: D000107:Acetylation; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D044127:Epigenesis, Genetic / Q000235:genetics* / Q000502:physiology; D005260:Female; D047109:Fetal Development / Q000235:genetics* / Q000502:physiology; D005317:Fetal Growth Retardation / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D015870:Gene Expression / Q000235:genetics / Q000502:physiology; D006657:Histones / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications* / Q000235:genetics / Q000503:physiopathology; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics* / Q000503:physiopathology; D015431:Weight Loss / Q000235:genetics* / Q000502:physiology
chemical_list: D006657:Histones
keywords: Epigenetic machinery; Fetal growth restriction; Histone deacetylases (HDACs); Liver; Lysine acetyltransferases (KATs); Maternal obesity; Placenta; Preconceptional weight loss