Gene expression patterns of insulin-like growth factor 1, insulin-like growth factor 2 and insulin-like growth factor binding protein 3 in human placenta from pregnancies with intrauterine growth restriction.
To investigate the expressions of the insulin receptor (IR), insulin receptor substrate-1 (IRS-1), insulin receptor substrate-2 (IRS-2), phosphatidyl inositol 3-kinase (PI3K) and insulin-like growth factor-1 (IGF-1) of the livers of the male adult rats born with intrauterine growth retardation (IUGR),and to find out the relationship between IUGR and insulin resistance in their adult life.
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).
In addition to imprinted genes, the microarray data highlighted non-imprinted genes acting in endocrine signaling (LEP, CRH, HPGD, INHBA), tissue growth (IGF1), immune modulation (INDO, PSG-family genes), oxidative metabolism (GLRX), vascular function (AGTR1, DSCR1) and metabolite transport (SLC-family solute carriers) as differentially expressed in IUGR vs. non-IUGR placentae.
These results demonstrate that the molecular machinery necessary for transcriptional control of proliferation remains intact in IUGR fetal myoblasts, indicating that in vivo factors such as reduced insulin and IGF1, hypoxia and/or elevated counter-regulatory hormones may be inhibiting muscle growth in IUGR fetuses.
Similar perturbations could be observed in human intrauterine growth retardation suggesting the IGF/IGFBP system is involved in fetal growth, biomineralization, and energetic status in humans.
In this hypothetical scenario, IUGR-induced deficit of IGF-1 causes "diabetic" aging trajectory associated with various metabolic disorders in adulthood, while fetal macrosomia-induced excessive levels of IGF-1 lead to "cancerous" aging trajectory.
The results showed FBG, FINS and HOAM-IR in CUG-FGR group were higher than those in high fat feeding control group (NC+HF), but the content of IGF-1 in blood was lower than that in NC + HF group.
Women in the IUGR group were smaller than in the control group (p < 0.05), and, using the covariance test (p < 0.05), this was found to be correlated with IGF-I levels but not with EGF or TGF-beta levels.
With the first descriptions of patients born small for gestational age carrying mutations within the insulin-like growth factor type 1 receptor (IGF-1R) gene, genetic defects at the lower end of the GH-IGF-1 axis were identified as a monogenetic cause of intrauterine growth retardation.
We investigated the effects of intra-amniotic IGF1 administration to ovine fetuses with uteroplacental embolisation-induced FGR on phenotypical and physiological characteristics in the 2 weeks after birth.
IGFs are low in human SGA newborns; however, only a small minority of these infants have mutations of IGF-related molecules, rather, idiopathic or maternal factors are thought to induce FGR in most of these cases.