We identified one case each of FGR and PIH showing hypomethylation of H19-DMR and IGF2-DMRs only in the placenta, but not in cord blood, from the first case/control set.
We used a well-characterized mouse model of FGR in which placental Igf-2 production is lost due to deletion of the placental specific <i>Igf-2</i> P<sub>0</sub> promotor.
In the functional significance of gene, low-density lipoprotein receptor-related protein 10 (LRP10) was significantly increased (6-fold) and insulin-like growth factor (IGF-2) was dramatically increased (17-fold) in the FGR cases.The results show that the important brain-related genes are predominantly down-regulated in the intrauterine growth restriction fetuses during the second trimester of pregnancy.
Insulin-like growth factor-II (IGF2) deficiency in humans, as well as in mice, leads to intrauterine growth restriction and decreased neonatal glycogen stores.
Finally alterations in vulnerable epigenetic marks of imprinted genes such as H19/IGF2, during early stages of embryonic development result in intrauterine growth restriction.
In addition, significantly elevated odds of FGR birth were associated with increasing DNA methylation of HSD11B2 and WNT2, and decreasing DNA methylation of IGF2.
Notably, at 28 weeks' gestation there was increased IGF2 (3.9-fold), placental growth hormone (2.7-fold), and IGF BP2 (2.1-fold) expression in maternal blood in women destined to develop FGR at term (P < .05).
A reduction in substrate supply in fetal life, resulting in chronic hypoxaemia and intrauterine growth restriction, results in increased cardiac IGF-1R, IGF-2 and IGF-2R gene expression; and there is also evidence for a role of the IGF-2 receptor in the ensuing cardiac hypertrophy.
Our results suggest the involvement of the IGF2 imprinted gene in placental function and fetal growth and the possible association of epigenetic alterations with the pathophysiology of fetal growth restriction.
Using quantitative approaches, we explored the epigenetic modulation of IGF2/H19 during human development in 60 normal and 66 idiopathic IUGR (Intrauterine Growth Restriction) pregnancies, studying embryonic (cord blood) and extraembryonic (placenta and umbilical cord) tissues.
A reduction in placental IGF2 could be an adaptive response to restrict fetal growth in the presence of abnormal placentation or a response to poor fetal growth itself.
Severe intrauterine growth retardation and atypical diabetes associated with a translocation breakpoint disrupting regulation of the insulin-like growth factor 2 gene.
A break point 184 kb upstream of the paternally derived IGF2 gene, separating it from some telomeric enhancers, resulted in reduced expression in some mesoderm-derived adult tissues causing intrauterine growth retardation, short stature, lactation failure, and insulin resistance with altered fat distribution.