Battaglia, F.C.

The tissue and plasma concentration of polyols and sugars in sheep intrauterine growth retardation (Article)

2010-08-01T00:00:00Z

In an ovine model of placental insufficiency-induced intrauterine growth retardation (PI-IUGR), characterized by hypoxia, hypoglycemia and a significant reduction in fetal weight, we assessed alterations in fetal and placental polyols. Arterial maternal-fetal concentration differences of glucose and mannose were greater in the PI-IUGR fetus; glucose: C (n = 7), 2.68 ± 0.14 mmol/L versus PI-IUGR (n = 9), 3.18 ± 0.16 mmol/L (P < 0.02) and mannose: C, 42.9 ± 8.1 μmol/L versus PI-IUGR, 68.5 ± 19.1 μmol/L (P < 0.001). For PI-IUGR fetuses, fetal arterial plasma myo-inositol concentrations were significantly increased (P < 0.001). The concentrations of sorbitol, glucose and fructose were significantly reduced (P < 0.03, 0.01, 0.02, respectively). The cotyledons of IUGR placentas had a significantly increased concentration of myoinositol (P < 0.003) and decreased concentrations of sorbitol, fructose and glycerol (P < 0.01, 0.02, 0.01, respectively). Fetal hepatic concentrations of sorbitol (P < 0.001) and fructose (P < 0.03) were also significantly reduced. These profound changes in both placental and fetal concentrations of polyols and sugars in sheep PI-IUGR pregnancies support the conclusion that within the PI-IUGR placenta there is an increased flux through the glucose 6-P:inositol 1-P cyclase system and decreased flux through the polyol dehydrogenase system, leading to increased placental myo-inositol production and decreased sorbitol production. The decreased placental supply of sorbitol to the fetal liver may lead to decreased fetal hepatic fructose production. These observations highlight that, in association with hypoxic and hypoglycemic PI-IUGR fetuses, there are major placental and fetal alterations in polyol production. The manner in which these alterations in fetoplacental carbohydrate metabolism contribute to the pathophysiology of PI-IUGR is currently unknown. Copyright

Development and Mechanisms of Fetal Hypoxia in Severe Fetal Growth Restriction (Article)

2007-07-01T00:00:00Z

Severe fetal growth restriction (FGR) is often associated with hypoxia. We studied FGR hypoxia in an experimental model which is produced by exposing pregnant ewes to a hyperthermic environment. The study utilized simultaneous measurements of several relevant factors, e.g., uterine and umbilical blood flows and O2uptakes. Sixteen ewes were divided equally into control (C) and hyperthermic (HT) groups. Hyperthermia (40 °C for 12 h/35 °C for 12 h; ∼35% relative humidity, RH) was maintained for 80 days commencing at approximately 38 days gestational age (dGA term 147 ± 3 days). All ewes were then placed in a control environment (∼21 °C, 24 h; ∼30% RH) and studied at approximately 134 dGA. Mean HT placental and fetal weights were 39% and 45% of C, respectively (p < 0.0001), umbilical O2uptake/kg fetus was 76% of C (p < 0.01) and umbilical venous PO2was reduced (20.2 vs. 29.7 Torr, p < 0.001). Contrary to the hypothesis that FGR hypoxia is due to maternal placental hypoperfusion, uterine flow was not reduced in relation to O2uptake. The uterine-umbilical venous PO2difference was enlarged (38 vs. 23 Torr, p < 0.0001). This difference is the expression of a balance between developmental changes in placental structure and oxidative metabolism, which have opposite effects in terms of fetal oxygenation. We postulate that FGR hypoxia results from disproportionate underdevelopment of those changes which allow for a progressive increase in umbilical O2uptake.

Effect of dexamethasone on fetal hepatic glutamine-glutamate exchange (Article)

2000-01-01T00:00:00Z

Intravenous infusion of dexamethasone (Dex) in the fetal lamb causes a two- to threefold increase in plasma glutamine and other glucogenic amino acids and a decrease of plasma glutamate to approximately one-third of normal. To explore the underlying mechanisms, hepatic amino acid uptake and conversion of L-[1-(13)C]glutamine to L-[1-(13)C]glutamate and (13)CO(2) were measured in six sheep fetuses before and in the last 2 h of a 26-h Dex infusion. Dex decreased hepatic glutamine and alanine uptakes (P < 0.01) and hepatic glutamate output (P < 0.001). Hepatic outputs of the glutamate (R(Glu,Gln)) and CO(2) formed from plasma glutamine decreased to 21 (P < 0.001) and 53% (P = 0.009) of control, respectively. R(Glu,Gln), expressed as a fraction of both outputs, decreased (P < 0.001) from 0.36 +/- 0.02 to 0.18 +/- 0.04. Hepatic glucose output remained virtually zero throughout the experiment. We conclude that Dex decreases fetal hepatic glutamate output by increasing the routing of glutamate carbon into the citric acid cycle and by decreasing the hepatic uptake of glucogenic amino acids.

Relationship of fetal alanine uptake and placental alanine metabolism to maternal plasma alanine concentration (Article)

1998-01-01T00:00:00Z

Uterine and umbilical uptakes of alanine (Ala) were measured in 10 ewes before (control) and during intravenous infusion of Ala, which increased maternal arterial Ala concentration from 115 +/- 14 to 629 +/- 78 microM (P < 0.001). In 8 of these ewes, placental Ala fluxes were traced by constant intravenous infusion of L-[3,3,3-2H3]Ala in the mother and L-[1-13C]Ala in the fetus. Rates are reported as micromoles per minute per kilogram fetus. Ala infusion increased uterine uptake (2.5 +/- 0.6 to 15.6 +/- 3.1, P < 0.001), umbilical uptake (3.1 +/- 0.5 to 6.9 +/- 0.8, P < 0.001), and net uteroplacental utilization (-0.7 +/- 0.8 to 8.6 +/- 2.7, P < 0.01) of Ala. Control Ala flux to fetus from mother (Rf,m) was much less than the Ala flux to fetus from placenta (Rf,p) (0.17 +/- 0.04 vs. 5. 0 +/- 0.6). Two additional studies utilizing L-[U-13C]Ala as the maternal tracer confirmed the small relative contribution of Rf,m to Rf,p. During maternal Ala infusion, Rf,m increased significantly (P < 0.02) but remained a small fraction of Rf,p (0.71 +/- 0.2 vs. 7.3 +/- 1.3). We conclude that maternal Ala entering the placenta is metabolized and exchanged for placental Ala, so that most of the Ala delivered to the fetus is produced within the placenta. An increase in maternal Ala concentration increases placental Ala utilization and the fetal uptake of both maternal and placental Ala.