Altered Epigenetic Profiles in the Placenta of Preeclamptic and Intrauterine Growth Restriction Patients

Abstract

Intrauterine growth restriction (IUGR) and preeclampsia (PE) are placental pathologies known to complicate pregnancy and cause neonatal disorders. To date, there is a limited number of studies on the genetic similarity of these conditions. DNA methylation is a heritable epigenetic process that can regulate placental development. Our objective was to identify methylation patterns in placental DNA from normal, PE and IUGR-affected pregnancies. DNA was extracted, and bisulfite was converted, prior to being hybridized for the methylation array. Methylation data were SWAN normalized and differently methylated regions were identified using applications within the USEQ program. UCSC’s Genome browser and Stanford’s GREAT analysis were used to identify gene promoters. The commonality among affected genes was confirmed by Western blot. We observed nine significantly hypomethylated regions, two being significantly hypomethylated for both PE and IGUR. Western blot confirmed differential protein expression of commonly regulated genes. We conclude that despite the uniqueness of methylation profiles for PE and IUGR, the similarity of some methylation alterations in pathologies could explain the clinical similarities observed with these obstetric complications. These results also provide insight into the genetic similarity between PE and IUGR and suggest possible gene candidates plausibly involved in the onset of both conditions.

FGR-associated placental insufficiency and capillary angiogenesis involves disruptions in human placental miRNAs and mRNAs

“…The relative amount of each transcript was calculated using the ΔΔCT method and normalized to the endogenous reference gene beta-actin. The reference gene was chosen based on literature review [ [36] , [37] , [38] , [39] ].…”

Placental DNA methylation analysis of selective fetal growth restriction in monochorionic twins reveals aberrant methylated CYP11A1 gene for fetal growth restriction

“…[12][13][14] A recent study has revealed the presence of common genes exhibiting differential methylation in both intrauterine growth restriction and preeclampsia, which suggested the genetic similarity between the two conditions. 15 The patterns of DNA methylation in human placenta have been demonstrated to be reliable and significantly associated with fetal growth, which could function as a potential marker for the intrauterine environment and fetal development. [16][17][18] Therefore, placental changes in FGR need a thorough study by the DNA methylation analysis using an efficient detection platform to acquire more information for placental methylome analyses.…”