Effects of chronic hypoxia in vivo on the expression of human placental glucose transporters.
Birth weight is reduced and the risk of preeclampsia is increased in human high altitude pregnancies. There has been little work to determine whether hypoxia acts directly to reduce fetal growth (e.g. reduced blood flow and oxygen delivery), or via changes in functional capacities such as nutrient transport. We therefore investigated the expression of a primary nutrient transporter, the GLUT1 glucose transporter and two in vitro markers of hypoxia (erythropoietin receptor, EPO-R, and transferrin receptor, TfR) in the syncytial microvillous (MVM) and basal membrane fractions (BMF) of 13 high (3100 m) and 12 low (1600 m) altitude placentas from normal term pregnancies. Birth weight was lower at 3100 m than at 1600 m despite similar gestational age, but none of the infants were clinically designated as fetal growth restriction. EPO-R, TfR and GLUT1 were examined by immunoblotting and maternal circulating erythropoietin and transferrin by ELISA. EPO-R was greater on the MVM (+75%) and BMF (+25%) at 3100 m. TfR was 32% lower on the MVM at 3100 m. GLUT1 was 40% lower in the BMF at 3100 m. Circulating EPO was greater at high altitude, while transferrin was similar, and neither correlated with their membrane receptors. BMF GLUT1 was positively correlated with birth weight at high, but not low altitude. In this in vivo model of chronic placental hypoxia, syncytial EPO-R increased as expected, while nutrient transporters decreased, opposite to what has been observed in vitro. Therefore, hypoxia acts to reduce fetal growth not simply by reducing oxygen delivery, but also by decreasing the density of nutrient transporters.
Zamudio
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S
Department of Obstetrics, Gynecology and Women's Health, New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103-2714, USA. stacy.zamudio@umdnj.edu
Baumann
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MU
Illsley
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NP
D000328:Adult; D000531:Altitude; D000532:Altitude Sickness / Q000378:metabolism; D001724:Birth Weight; D002908:Chronic Disease; D005260:Female; D005786:Gene Expression Regulation; D051272:Glucose Transporter Type 1 / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D017467:Receptors, Erythropoietin / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism
D051272:Glucose Transporter Type 1; D017467:Receptors, Erythropoietin; D011990:Receptors, Transferrin