Glucose transport and system A activity in syncytiotrophoblast microvillous and basal plasma membranes in intrauterine growth restriction.
The mechanisms underlying the reduced fetal plasma concentrations of amino acids and glucose associated with intrauterine growth restriction (IUGR) remain to be fully established. The activity of the amino acid transporter system A has been shown to be reduced in the syncytiotrophoblast microvillous membrane (MVM) in IUGR, however the impact of these changes on transplacental transport is difficult to assess without information on system A activity in the basal plasma membrane (BM). In this study we measured system A activity and mediated D-glucose uptake using radiolabelled substrates and rapid filtration techniques, and glucose transporter isoform 1 (GLUT 1) protein expression using Western blots in MVM and BM isolated from human placentas. In term IUGR (n=11) MVM system A activity was unaltered compared to controls (n=9). In contrast, system A activity in MVM was reduced by 50 per cent (P< 0.05) in preterm IUGR (n=8, gestational age 28-36 weeks) as compared to controls (n=8, gestational age 28-35 weeks). BM system A activity was unaltered in both IUGR groups. Similarly, MVM and BM GLUT 1 expression and mediated D-glucose uptake was not affected by IUGR. In all preterm IUGR pregnancies signs of severe fetal compromise were present whereas term IUGR fetuses were less affected. These data support the view that MVM system A activity is related to the severity of compromise in IUGR. The markedly reduced system A activity in MVM in preterm IUGR together with the unaltered activity in BM is consistent with a decreased transplacental transport of neutral amino acids in this pregnancy complication. The hypoglycemia present in utero in some IUGR fetuses is not caused by a decreased glucose transport capacity across the syncytiotrophoblast plasma membranes.
Jansson
T
T
Perinatal Center, Department of Physiology & Pharmacology, Göteborg University, Sweden. thomas.jansson@fysiologi.gu.se
Ylvén
K
K
Wennergren
M
M
Powell
T L
TL
D000328:Adult; D026924:Amino Acid Transport System A / Q000378:metabolism*; D015153:Blotting, Western; D002458:Cell Fractionation; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism*; D005947:Glucose / Q000493:pharmacokinetics; D051272:Glucose Transporter Type 1; D006801:Humans; D008871:Microvilli / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D011247:Pregnancy; D014327:Trophoblasts / Q000378:metabolism*
D026924:Amino Acid Transport System A; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; C495677:SLC2A1 protein, human; D005947:Glucose