Insulin-like growth factors and their binding proteins in the term and preterm human fetus and neonate with normal and extremes of intrauterine growth.

Abstract

Insulin-like growth factors (IGFs), IGF-binding proteins (IGFBPs), and insulin are believed to be important in the regulation of fetal and neonatal growth. We previously reported that the profiles of IGFBPs in fetal cord serum (FCS) were dependent on the growth/metabolic status of the fetus. The goals of the current study were to examine the IGF system in FCS from term fetuses with normal growth, those with intrauterine growth retardation (IUGR), and those who were large for gestational age (LGA) and in FCS from normal weight preterm (25-37 weeks) and term fetuses in the neonatal period from the day of birth (day 0) until 7 days of age (day 7). Western ligand blotting (WLB) of term FCS revealed IGFBPs with mol wt of 43 and 38 kilodaltons (kDa; IGFBP-3), 34 kDa (IGFBP-2), 28 kDa (IGFBP-1 and glycosylated IGFBP-4), and 24 kDa (IGFBP-4). In IUGR FCS, there was a 50% decrease in IGFBP-3 detected by WLB, which was shown not to be due to an IGFBP-3 protease in IUGR sera. In LGA FCS, IGFBP-3 levels were elevated 2-fold by densitometric analysis of ligand blots. In normal term FCS, the following levels (+/- SE) were present: IGF-I, 76 +/- 16; IGF-II, 401 +/- 38; IGFBP-3, 700 +/- 112; IGFBP-1, 77 +/- 10 ng/mL; and insulin, 3.8 +/- 1.6 microU/mL. In IUGR FCS, IGF-I, IGF-II, and IGFBP-3 were significantly reduced, and IGFBP-1 was 7-fold higher than in FCS from normal weight fetuses. In LGA FCS, IGF-I, insulin, and IGFBP-3 were significantly increased, whereas IGFBP-1 was significantly decreased. During the neonatal period, IGF-I levels on day 0 were 4-fold higher in FCS from term (38-40 weeks) compared to preterm (25-31 weeks) newborns. FCS IGF-II levels did not change significantly on day 0 between 25-40 weeks gestation. In the first 7 days of postnatal life, IGF-I levels were unchanged in preterm newborns, whereas in term neonates, IGF-I levels decreased precipitously on day 1, remained low during the first 3 days of life, and returned to birth levels by the end of the first week. In contrast, IGF-II and IGFBP-3 levels did not significantly change during the first week of life in preterm or term newborns.(ABSTRACT TRUNCATED AT 400 WORDS)

Genomic imprinting as an adaptative model of developmental plasticity

“…In human studies much effort has focussed on establishing whether circulating foetal IGF2 levels correlate with foetal growth. However, the evidence is conflicting, as a variety of studies which have found that IGF2 levels in the placenta and/or cord blood correlate positively with birth weight [55][56][57][58][59], while others find no such relationship [60][61][62][63][64]. The discrepancies may partly be due to a failure to take into account the impact of changes in the levels of the circulating non-imprinted binding proteins which alter IGF2 bioavailability, IGFBPs.…”

“…The discrepancies may partly be due to a failure to take into account the impact of changes in the levels of the circulating non-imprinted binding proteins which alter IGF2 bioavailability, IGFBPs. Serum level of several IGFBPs has been found to correlate with birth weight and may be modulated by in utero nutrition [57,58,61,65]. This relationship with proteins which modulate bioavailability makes Igf2 a particularly challenging model for assessing phenotypic plasticity and imprinted gene dosage and also suggests that the effective dosage of imprinted genes may be modulated post transcriptionally by non-imprinted pathways.…”

Genetic disorders in the GH–IGF-I axis in mouse and man

“…However, controversy exists with regard to the relation between fetal serum IGF-II levels and fetal growth. Some studies report reduced cord blood IGF-II levels in IUGR babies (38)(39)(40), while others report similar levels of IGF-II in IUGR and normal fetuses (41). Human mutations in the gene encoding IGF-II, located on 11p15, have not been identified so far.…”

Low IGF-I suppresses VEGF-survival signaling in retinal endothelial cells: Direct correlation with clinical retinopathy of prematurity

“…IGF-I is an important somatic growth factor that is correlated with birth weight (14,15) and gestational age (16,17). In particular, IGF-I is not maintained at in utero levels after premature birth (16) perhaps because of loss of IGF-I sources from placenta and from amniotic fluid that is ingested by the fetus.…”