ABSTRACT. We determined the extent to which ligating both maternal uterine arteries affects fetal hepatic energy and redox states in the fetal rat. Bilateral maternal uterine artery ligation on d 18 of the rat's 21.5-d gestation significantly inhibits fetal growth; sham surgery limits growth to a lesser extent. Within 12 h of surgery and persisting to d 19, small-for-gestational age (SGA) fetuses had significantly diminished ATPIADP and adenylate charge ratios, whereas sham fetuses had values intermediate between SGA and normal. Hepatic mitochondrial redox state demonstrated similar changes. Cytosolic redox state in SGA fetuses at 12 and 24 h after surgery was significantly elevated. SGA fetuses had significantly diminished plasma insulin and elevated glucagon concentrations. On d 19 and 20, hepatic ATPIADP and cytosolic NAD+/NADH correlated directly for sham and normal but not SGA fetuses. Alterations in glucose, insulin, and glucagon availability and hypoxia were responsible for the changes in energy and redox states. They may also have disassociated hepatic cytosolic from mitochondrial redox states and altered the equilibrium between adenine and nicotinamide nucleotides. These altered cellular functions retarded fetal growth. Newborn SGA, sham, and normal rat pups had similar hepatic ATPIADP, cytosolic, and mitochondrial redox states at 10 and 240 min after delivery suggesting that the hypoglycemia which developed in SGA pups was not attributable to alterations in these variables. (Pediatr Res 27: 56-63,1990) Abbreviations AC, acetoacetate SGA, small-for-gestational age Intrauterine growth retardation is often ascribed to "uteroplacental insufficiency," a poorly defined clinical term suggesting compromised maternal-fetal relations (1). To determine the factors responsible for intrauterine growth retardation, we performed bilateral uterine artery ligation in the maternal rat. This technique, which can be considered an extreme example of "uteroplacental insufficiency," alters a number of physiologic variables including gaseous exchange and metabolic fuel availability. Alterations in these variables are known to affect fetal growth; however, the mechanisms by which this occurs are not completely understood. Particularly unclear is the impact of these alterations on cellular metabolic processes. For these reasons we Our data indicate that bilateral maternal uterine artery ligation in the rat acutely decreases fetal hepatic ATP/ADP and mitochondrial NAD+/NADH relations but increases cytosolic NAD+/NADH. These changes and alterations in other physiologic variables contributed to development of fetal growth retardation. During the neonatal period, ATP/ADP, adenylate charge ratio, and redox states increase appropriately in SGA newborn rat pups. Alterations in these variables are not directly responsible for the hypoglycemia that develops in the SGA newborn rat.
MATERIALS AND METHODSSurgery. We have reported the details of our surgical techniques (2). In brief, on d 18 of their 2 1.5-d gestation, we assigned timed...