Altered gas exchange, limited glucose and branched chain amino acids, and hypoinsulinism retard fetal growth in the rat

Abstract

We measured several growth stimulating variables in growth retarded (small-for-gestational-age [SGA]) rat fetuses on days 18, 19, 20, and 21 of their 21.5-day gestation. Bilateral maternal uterine artery ligation on day 18 was used to retard fetal growth, and fetuses of sham and nonoperated (normal) mothers served as controls. SGA fetuses had the lowest body and placental weights, while sham fetuses had intermediate weights from days 19 to 21. Similarly, SGA fetuses had the most profound alterations in arteriovenous PO 2, PCO 2, and pH, while sham fetuses had significant but less severe alterations. Fetal plasma concentrations and fetal/maternal ratios of glucose were significantly diminished in SGA fetuses on days 18 and 19; sham fetuses had intermediate values on day 19. Plasma concentrations and fetal/maternal ratios of leucine, isoleucine, and valine, but not the other amino acids, were significantly diminished in SGA fetuses on days 18, 19, and 20. Plasma insulin concentrations were significantly diminished in SGA fetuses on days 19 and 20, and hepatic concentrations of glycogen were significantly diminished on all days. Despite significantly elevated plasma glucagon concentrations in SGA fetuses, hepatic cytosolic phosphoenolpyruvate carboxykinase (PEPCK) activity was not elevated. These data indicate that bilateral uterine artery ligation retards fetal growth in the rat by altering gas exchange and limiting fuel availability. The limited insulin in SGA fetuses might further have retarded growth. Despite the acknowledged role of glucagon as a potent stimulator of gluconeogenic enzyme induction during the perinatal period, significantly elevated glucagon concentrations in the SGA fetus failed to stimulate PEPCK.