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

Progress in the understanding of the etiology and predictability of fetal growth restriction

“…In contrast, the unmethylated maternal ICR1 activates H19 expression. The placenta from women diagnosed with FGR showed significantly enhanced expression of H19 and decreased methylation in its promoter, which is consistent with a notion that H19 produces an untranslated RNA that suppresses growth (Koukoura et al 2011b, Piyasena et al 2015. Although DNA methylation at ICR1 is proven to affect IGF2 expression, the methylation level at ICR1 is not significantly reduced in FGR placentas (Guo et al 2008, Bourque et al 2010.…”

“…Significantly decreased IGF2 mRNA levels were observed in the human placentas from pregnancies complicated by FGR. This was attributed to altered DNA methylation and relaxation of imprinting (Koukoura et al 2011a). In a FGR mouse model manipulated by caloric restriction, the expression of glucose transporter, Glut3, a predominant isoform of trans-placental glucose transporter, was decreased in the placentas compared to the controls.…”

Placental 5-methylcytosine and 5-hydroxymethylcytosine patterns associate with size at birth

“…13 Approximately 50% of growthrestricted individuals with SRS cases show loss of methylation at ICR1, which could lead to decreased IGF2 expression and consequent growth restriction. 8,14 IGF2 expression is additionally modulated by DNA methylation at a number of other DMRs, 15 and altered placental and umbilical cord 5mC at DMRs controlling IGF2 expression has been reported in association with fetal growth restriction in some, [16][17][18][19] but not all 15,20 studies.…”

Glucose as a fetal nutrient: dynamic regulation of several glucose transporter genes by DNA methylation in the human placenta across gestation

“…DNA methylation is the most widely studied epigenetic phenomenon, previously demonstrated to play an important role in placental function and to be dynamic in the human placenta, both across gestation and in response to cumulative environmental and stochastic factors [18]. Additionally, disruption of placental methylation profile has been implicated in several pathologies, including fetal growth restriction and gestational diabetes mellitus [19][20][21][22][23][24][25]. In light of these data and the potential for epigenetic mechanisms to play an important role in regulating nutrient transport in the placenta, we have investigated the relationship between GLUT family member expression and promoter methylation in the human placenta across gestation using publicly available genome-scale DNA methylation and gene expression array data.…”