MATERNAL HYPOXIA AS A MODEL FOR INTRAUTERINE GROWTH-RETARDATION - EFFECTS ON INSULIN-LIKE GROWTH-FACTORS AND THEIR BINDING-PROTEINS

Evidence suggests that IGF and their binding proteins play a role in f etal growth, but more knowledge concerning their regulation is essenti al. We examined the expression of IGF and their binding proteins in ex perimental intrauterine growth-retarded (IUGR) rat fetuses of hypoxic dams (13-14% oxygen, d 14-21 of gestation). The mean body weight of th e fetuses (d 21 of gestation, n = 72) of the six hypoxic dams was 24% lower (p < 0.0001) than the mean weight of the fetuses of six control dams (n = 82). Wet liver weights demonstrated a 20% decrease (p < 0.00 01) and placentas a 10% decrease (p < 0.01) compared with control fetu ses. The mean serum concentrations of immunoreactive IGF-I in both gro ups were low but did not differ significantly. The mean serum concentr ations of immunoreactive IGF-II, however, were higher in IUGR fetuses. As assessed by Northern blot analysis, there was a 4-fold increase in insulin-like growth factor binding protein-1 (IGFBP-1) mRNA expressio n in the livers of the IUGR fetuses compared with controls. IGFBP-2 mR NA expression was 6-fold increased in IUGR fetal livers. No difference was found in IGFBP-4 mRNA. An increase in IGFBP-1, -2, and -4 concent rations could be seen by Western ligand blotting in the serum of growt h-retarded fetuses compared with control fetuses. This finding was ver ified by immunoprecipitation with specific antibodies, which demonstra ted increases in IGFBP-1 and IGFBP-2. Our results validate the use of maternal hypoxia as an experimental model of intrauterine growth retar dation and indicate that increased IGFBP-1 and -2 expression may be of importance in the etiology of fetal growth retardation caused by mate rnal hypoxia.