title: DNA methylation of the p66Shc promoter is decreased in placental tissue from women delivering intrauterine growth restricted neonates.
abstract: OBJECTIVE
  The adaptor protein p66Shc generates mitochondrial reactive oxygen species and translates oxidative signals into apoptosis. We aimed to analyze potential alterations in total methylation and in p66Shc activation in placental tissues from women delivering intrauterine growth restricted neonates (IUGR) versus appropriate for gestational age (AGA) and small for gestational age (SGA) neonates.
  
  
  METHODS
  DNA methylation of the p66Shc promoter and of long interspersed nuclear elements (LINE-1), as a marker for total methylation, was quantified by automatic pyrosequencing in 15 IUGR, 25 AGA and 15 SGA placentas. Placental gene expression of p66Shc was determined by TaqMan real-time polymerase chain reaction.
  
  
  RESULTS
  No significant difference was found for LINE-1 methylation between IUGR, AGA and SGA newborns. DNA methylation of the p66Shc promoter was significantly decreased in the IUGR compared with the AGA group (p < 0.0001) and the SGA group (p < 0.0001). However, analysis of placental p66Shc gene expression did not show a significant difference between the three groups.
  
  
  CONCLUSIONS
  It remains speculative if the decreased p66Shc promoter methylation might play a role in the pathophysiology of endothelial dysfunction and cardiovascular disease after IUGR.
authors.affiliation: Pediatrics, University of Erlangen-Nuremberg, Erlangen, Germany. anja.tzschoppe@uk-erlangen.de
authors.forename: Anja
authors.initials: A
authors.lastname: Tzschoppe
authors.forename: Helmuth
authors.initials: H
authors.lastname: Doerr
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rascher
authors.forename: Tamme
authors.initials: T
authors.lastname: Goecke
authors.forename: Matthias
authors.initials: M
authors.lastname: Beckmann
authors.forename: Ralf
authors.initials: R
authors.lastname: Schild
authors.forename: Ellen
authors.initials: E
authors.lastname: Struwe
authors.forename: Jürgen
authors.initials: J
authors.lastname: Geisel
authors.forename: Heike
authors.initials: H
authors.lastname: Jung
authors.forename: Jörg
authors.initials: J
authors.lastname: Dötsch
mesh_terms: D019175:DNA Methylation; D036861:Delivery, Obstetric; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics*; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D008297:Male; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D055765:Shc Signaling Adaptor Proteins / Q000235:genetics* / Q000378:metabolism; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1
chemical_list: C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1