Effects of acute hypoxemia on insulin-like growth factors and their binding proteins in fetal sheep

Abstract

It has been proposed that insulin-like growth factor I (IGF-I) regulates fetal growth and differentiation. Plasma IGF-I concentrations correlate positively with fetal nutrient availability and newborn birth weights. To explore the hypothesis that hypoxemia decreases fetal growth by decreasing fetal IGF-I availability, we instrumented 14 fetal sheep with vascular catheters. At least 4 days after surgery, 10 fetuses were made acutely hypoxemic by infusing nitrogen into the maternal trachea for 3 h. Fetal blood oxyhemoglobin saturation decreased from 53 +/- 6 (SD) to 31 +/- 9%. Concomitantly, plasma IGF-I concentrations decreased from 91 +/- 11 to 67 +/- 10 ng/ml and IGF-I binding protein-1 concentration increased significantly, as assessed by ligand and Western blot analysis. Fetal IGF-I concentrations remained below control values throughout a subsequent recovery period (68 +/- 12 ng/ml at 6 h). In four control fetuses and in the ewes, plasma IGF-I concentrations were not significantly different from control values (97 +/- 18 and 181 +/- 18 ng/ml, respectively). These data support the hypothesis that decreases in fetal oxygen availability may decrease fetal growth by decreasing IGF-I production and availability.