title: Epigenetic dysregulation of the IGF system in placenta of newborns exposed to maternal impaired glucose tolerance.
abstract: OBJECTIVE
  To determine whether placental IGF1R, IGFBP3, INSR and IGF1 DNA methylation and mRNA levels were dysregulated when exposed to maternal impaired glucose tolerance (IGT) and investigate whether the epigenetic profile is associated with feto-placental developmental markers.
  
  
  METHODS
  The IGT diagnosis was made according to the WHO criteria (IGT: n = 34; normal glucose tolerance [NGT]: n = 106). DNA methylation and mRNA levels were quantified using bisulfite pyrosequencing and qRT-PCR, respectively.
  
  
  RESULTS
  IGF1R and IGFBP3 DNA methylation levels were lower in placentas exposed to IGT compared with NGT (-4.3%; p = 0.021 and -2.5%; p = 0.006 respectively) and correlated with 2-h post-oral glucose tolerance test (OGTT) glycemia (r = -0.23; p = 0.010 and r = -0.20; p = 0.028, respectively). IGF1R mRNA levels were associated with newborns' growth markers (e.g., birth weight; r = 0.20; p = 0.032).
  
  
  CONCLUSIONS
  These results support the growth-promoting role of the IGF system in placental/fetal development and suggest that the IGF1R and IGFBP3 DNA methylation profiles are dysregulated in IGT, potentially affecting the fetal metabolic programming.
authors.affiliation: Department of Biochemistry, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Véronique
authors.initials: V
authors.lastname: Desgagné
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Hivert
authors.forename: Julie
authors.initials: J
authors.lastname: St-Pierre
authors.forename: Simon-Pierre
authors.initials: SP
authors.lastname: Guay
authors.forename: Jean-Patrice
authors.initials: JP
authors.lastname: Baillargeon
authors.forename: Patrice
authors.initials: P
authors.lastname: Perron
authors.forename: Daniel
authors.initials: D
authors.lastname: Gaudet
authors.forename: Diane
authors.initials: D
authors.lastname: Brisson
authors.forename: Luigi
authors.initials: L
authors.lastname: Bouchard
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics; D001786:Blood Glucose; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D018149:Glucose Intolerance; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology*; D007231:Infant, Newborn; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D008297:Male; D010920:Placenta / Q000503:physiopathology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D017526:Receptor, IGF Type 1 / Q000235:genetics*; D011972:Receptor, Insulin / Q000235:genetics
chemical_list: D015703:Antigens, CD; D001786:Blood Glucose; C583557:IGF1 protein, human; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; C435941:INSR protein, human; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin