title: Uteroplacental carbon substrate metabolism and O2 consumption after long-term hypoglycemia in pregnant sheep.
abstract: Chronic maternal hypoglycemia leads to fetal growth restriction, but the effects on placental metabolism and its contribution to reduced fetal growth have not been determined. To study these factors, experiments were conducted in seven normal control (C) and six chronically insulin-infused hypoglycemic (H) pregnant sheep over the second half of gestation to measure effects of maternal and fetal hypoglycemia [maternal: 2.0 +/- 0.2 (H) vs. 3.6 +/- 0.1 mM (C); fetal: 0.7 +/- 0.1 (H) vs. 1.1 +/- 0.1 mM (C)] on placental metabolism of glucose, other carbon substrates, and O2. Placental and fetal weight were proportionately reduced in the H group [placental wt: 258 +/- 18 (H) vs. 376 +/- 18 g (C), -31%; fetal wt: 2,540 +/- 190 (H) vs. 3,558 +/- 230 g (C), -29%]. Glucose uptake by the uterus was reduced in the H group [0.10 +/- 0.01 (H) vs. 0.19 +/- 0.02 mmol/min (C)]; it was partitioned more to uteroplacental consumption (UPGC) and less to transfer to the fetus (PGT) [UPGC-to-PGT ratio: 20.0 +/- 2.1 (H) and 13.5 +/- 1.2 (C), P < 0.05 for both]. Metabolism of glucose by nonoxidative and oxidative pathways (as estimated by uteroplacental lactate production-to-UPGC ratio and normal rates of placental O2 consumption) was not significantly changed in the H group. Acetoacetate and beta-hydroxybutyrate net uptake and fructose production rates were significantly reduced in the H group, and there was no change in free fatty acid or amino acid uptake rates. With acute return of maternal and fetal glucose concentrations to normal, UPGC and PGT exceeded normal rates by approximately 25%. Thus chronic reduced glucose supply to the uteroplacenta produces a smaller placenta that uses glucose normally and in preference to transfer to the fetus, demonstrating placental metabolic autonomy at the expense of the fetus.
authors.affiliation: Department of Pediatrics, University of Colorado School of Medicine, Denver 80262, USA.
authors.forename: T D
authors.initials: TD
authors.lastname: Carver
authors.forename: W W
authors.initials: WW
authors.lastname: Hay
mesh_terms: D000818:Animals; D002244:Carbon / Q000378:metabolism*; D002908:Chronic Disease; D005314:Embryonic and Fetal Development; D005260:Female; D005333:Fetus / Q000502:physiology; D007003:Hypoglycemia / Q000503:physiopathology*; D010101:Oxygen Consumption; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications; D012756:Sheep; D013379:Substrate Specificity; D014599:Uterus / Q000378:metabolism*
chemical_list: D002244:Carbon