Glucose metabolism in the human preterm and term placenta of IUGR fetuses.
Many fetuses suffering from intrauterine growth restriction (IUGR) are hypoglycaemic. However, the underlying mechanisms are not well established. An increased placental glucose consumption in IUGR could impair glucose transfer across the placenta. In this study we used two different approaches to investigate glucose metabolism in preterm and term placentae of IUGR fetuses. We determined activity and protein expression of the three rate-limiting glycolytic enzymes phosphofructo kinase (PFK), pyruvate kinase (PK) and hexokinase (HXK) in a cytoplasmic fraction of homogenates of placentae obtained from IUGR and appropriate for gestational age (AGA) pregnancies. Protein expression was assessed using Western blot and enzyme activities were determined in a spectrophotometer by measuring the rate of NADH oxidation (PFK and PK) or NADP reduction (HXK) in enzyme reactions coupled to the respective enzyme. To determine the distribution of the glycolytic enzymes immunocytochemistry was performed. We also measured glucose consumption and lactate production in fresh placental villous tissue using a perifusion system. The expression of PFK, PK and HXK as well as the activity of PK and HXK was unaltered in IUGR placentae. The activity of PFK on the other hand was 32 per cent lower in IUGR placentae (n=24, P<0.05). Immunocytochemistry confirmed the distribution of the enzymes to the cytoplasm of the syncytiotrophoblast. Placental glucose consumption in IUGR [0.06+/-0.01 micromol/(min*g), n=5] was not different from AGA [0.06+/-0.005 micromol/(min*g), n=12], whereas lactate production was decreased by 28 per cent in IUGR. These results do not support the hypothesis of increased placental glucose consumption but suggest an altered glycolytic pathway in the IUGR placenta.
Magnusson
A L
AL
Department of Physiology and Pharmacology, Perinatal Center, Göteborg University, Medicinaregatan 11, Box 432, s-405 30 Göteborg, Sweden. Anneliese.Magnusson@fysiologi.gu.se
Powell
T
T
Wennergren
M
M
Jansson
T
T
D000328:Adult; D001692:Biological Transport; D002824:Chorionic Villi / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation / Q000201:enzymology* / Q000473:pathology; D005865:Gestational Age; D005947:Glucose / Q000378:metabolism*; D006593:Hexokinase / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D010477:Perfusion; D025221:Phosphofructokinases / Q000378:metabolism; D010920:Placenta / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011770:Pyruvate Kinase / Q000378:metabolism
D019344:Lactic Acid; D025221:Phosphofructokinases; D006593:Hexokinase; D011770:Pyruvate Kinase; D005947:Glucose