DNA methylation of the p66Shc promoter is decreased in placental tissue from women delivering intrauterine growth restricted neonates. (26th March 2013)

• Record Type: Journal Article
• Authors: Tzschoppe, Anja; Doerr, Helmuth; Rascher, Wolfgang; Goecke, Tamme; Beckmann, Matthias; Schild, Ralf; Struwe, Ellen; Geisel, Jürgen; Jung, Heike; Dötsch, Jörg
• Is Part Of: Prenatal diagnosis. Volume 33:Number 5(2013:May)
• Page Start: 484
• Page End: 491
• Publication Date: 2013-03-26
• Subjects: Prenatal diagnosis -- Periodicals; Fetus -- Diseases -- Diagnosis -- Periodicals; Electronic journals; 618.32075
• DOI: 10.1002/pd.4096
• Languages: English
• ISSNs: 0197-3851

Abstract

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. Method: 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. Conclusion: It remains speculative if the decreased p66Shc promoter methylation might play a role in the pathophysiology of endothelial dysfunction and cardiovascular disease after IUGR. © 2013 John Wiley & Sons, Ltd. Abstract : What's already known about this topic? Previous studies assessed epigenetic dysregulation as potential mechanism in the developmental programming of disease after intrauterine growth restriction (IUGR). What does this study add? We analyzed promoter methylation and gene expression of the mitochondrial adaptor protein p66Shc and found decreased p66Shc promoter methylation in placental tissue of IUGR versus appropriate for gestational age and small for gestational age neonates. Whether this plays a role in the pathophysiology of disease after IUGR remains speculative.