Hypomethylation along with increased H19 expression in placentas from pregnancies complicated with fetal growth restriction

Abstract

The expression of imprinted genes is regulated by epigenetic modifications, such as DNA methylation. Many imprinted genes are expressed in the placenta and affect nutrient transfer capacity of the placental exchange barrier. The H19 gene is abundantly expressed by the human placenta and is implicated in the pathogenesis of congenital growth disorders such as Beckwith-Wiedemann (BWS) and Silver-Russell (SRS) syndromes. The aim of this study was to investigate the role of DNA methylation on H19 transcription and imprinting, in the pathophysiology of fetal growth restriction (FGR). Thirty one and 17 placentas from FGR-complicated and normal pregnancies were collected, respectively. We studied gene transcription, genotyping and methylation analysis of the AluI H19 on exon 5 polymorphism. Placental expression levels of H19 were significantly increased in the FGR group. The H19 mRNA levels were similar between normal placental samples that demonstrated loss and maintenance of imprinting. Placentas from growth-restricted pregnancies had lower methylation levels compared to normals, in the H19 promoter region. We have demonstrated an increased H19 transcription in the FGR group of placentas. The hypomethylation of the H19 promoters is compatible with the aberrant expression. The association of these two findings is reported for the first time in placental tissues, however, its significance remains unknown. Whether the results of this study represent an adaptation of the placenta to hypoperfusion, or they are part of FGR pathophysiology has to be further investigated.