The tissue and plasma concentration of polyols and sugars in sheep intrauterine growth retardation.

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 micromol/L versus PI-IUGR, 68.5 +/- 19.1 micromol/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 myo-inositol (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.