Chronic maternal hypoxia retards fetal growth and increases glucose utilization of select fetal tissues in the rat.

The development of intrauterine growth retardation (IUGR) is frequently associated with fetal hypoxia, hypoglycemia, and abnormal fetal glucose metabolism. To determine the effects of hypoxia (without concomitant hypoglycemia) on fetal glucose metabolism, we continuously exposed pregnant rats to 10% (10.1 kPa) ambient oxygen from day 15 through day 20 of gestation (term, 21.5 days) and used radiolabeled 2-deoxyglucose (2DG) to measure in vivo relative glucose utilization (rGU) of several fetal tissues on day 20 of gestation. Pair-fed rats in room-air oxygen were used as controls. Maternal hypoxia resulted in significant IUGR, fetal hypoxia and acidosis, and fetal lactate accumulation on day 20 of gestation. Following 5 days of hypoxia, rGU values for fetal lung, heart, and kidney were increased by 61%, 54%, and 47%, respectively (P < .05). rGU values for fetal brain, liver, muscle, and placenta were not significantly affected. Fetal plasma glucose concentrations were similar in hypoxic and control fetuses. We speculate that the increased rGU of hypoxic fetal tissues is due in part to anaerobic metabolism and increased glycolysis.

Intrauterine growth retardation: fetal glucose transport is diminished in lung but spared in brain.

"Uteroplacental insufficiency" often causes asymmetric fetal growth retardation. Glucose transporters control cell glucose utilization and thus may be critical in the control of fetal growth. We hypothesized that uteroplacental insufficiency might alter glucose transporter activity, protein, and gene expression and thereby affect discordant organ growth in small-for-gestational-age (SGA) fetuses. We performed bilateral uterine artery ligation in pregnant rats on d 19 of gestation (term-21.5 d) to cause uteroplacental insufficiency and obtained fetal brain and lung tissue on d 20. The brain mass of SGA fetuses did not differ from that of sham and normal fetuses, but lung mass was significantly diminished. Glucose transport, measured with [3H]2-deoxyglucose, was similar in glial cells and brain tissue of SGA, sham, and normal fetuses. In contrast, type II pneumocytes, lung fibroblasts, and lung tissue of SGA fetuses had significantly decreased glucose transport. The intrinsic activity of the glucose transporter (Km) was not altered in the brain or lung of SGA fetuses. Total glucose transporter protein measured by cytochalasin-B binding and glucose transporter 1 mRNA was diminished in SGA lung tissue and type II pneumocytes, but not in SGA brain tissue or glial cells. We could not detect glucose transporter 3 mRNA in significant quantity in any tissue. With uteroplacental insufficiency, glucose transport is differentially altered in lung and brain. Glucose transporter protein and gene expression are diminished in the lung and normal in the brain of SGA fetuses. These changes may contribute to fetal growth retardation and the phenomenon of "brain sparing."