C Janzen1, M Y Y Lei, J Cho, P Sullivan, B-C Shin, S U Devaskar. 1. Department of Obstetrics and Gynecology, Division of Perinatology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. Electronic address: cjanzen@mednet.ucla.edu.
Abstract
INTRODUCTION: Transport of glucose from maternal blood across the placental trophoblastic tissue barrier is critical to sustain fetal growth. The mechanism by which GLUTs are regulated in trophoblasts in response to ischemic hypoxia encountered with intrauterine growth restriction (IUGR) has not been suitably investigated. OBJECTIVE: To investigate placental expression of GLUT1, GLUT3 and GLUT4 and possible mechanisms of GLUT regulation in idiopathic IUGR. METHODS: We analyzed clinical, biochemical and histological data from placentas collected from women affected by idiopathic full-term IUGR (n = 10) and gestational age-matched healthy controls (n = 10). RESULTS: We found increased GLUT3 protein expression in the trophoblast (cytotrophoblast greater than syncytiotrophoblast) on the maternal aspect of the placenta in IUGR compared to normal placenta, but no differences in GLUT1 or GLUT4 were found. No differential methylation of the GLUT3 promoter between normal and IUGR placentas was observed. Increased GLUT3 expression was associated with an increased nuclear concentration of HIF-1α, suggesting hypoxia may play a role in the up-regulation of GLUT3. DISCUSSION: Further studies are needed to elucidate whether increased GLUT3 expression in IUGR is a marker for defective villous maturation or an adaptive response of the trophoblast in response to chronic hypoxia. CONCLUSIONS: Patients with IUGR have increased trophoblast expression of GLUT3, as found under the low-oxygen conditions of the first trimester. Published by Elsevier Ltd.
INTRODUCTION: Transport of glucose from maternal blood across the placental trophoblastic tissue barrier is critical to sustain fetal growth. The mechanism by which GLUTs are regulated in trophoblasts in response to ischemic hypoxia encountered with intrauterine growth restriction (IUGR) has not been suitably investigated. OBJECTIVE: To investigate placental expression of GLUT1, GLUT3 and GLUT4 and possible mechanisms of GLUT regulation in idiopathic IUGR. METHODS: We analyzed clinical, biochemical and histological data from placentas collected from women affected by idiopathic full-term IUGR (n = 10) and gestational age-matched healthy controls (n = 10). RESULTS: We found increased GLUT3 protein expression in the trophoblast (cytotrophoblast greater than syncytiotrophoblast) on the maternal aspect of the placenta in IUGR compared to normal placenta, but no differences in GLUT1 or GLUT4 were found. No differential methylation of the GLUT3 promoter between normal and IUGR placentas was observed. Increased GLUT3 expression was associated with an increased nuclear concentration of HIF-1α, suggesting hypoxia may play a role in the up-regulation of GLUT3. DISCUSSION: Further studies are needed to elucidate whether increased GLUT3 expression in IUGR is a marker for defective villous maturation or an adaptive response of the trophoblast in response to chronic hypoxia. CONCLUSIONS:Patients with IUGR have increased trophoblast expression of GLUT3, as found under the low-oxygen conditions of the first trimester. Published by Elsevier Ltd.
Entities:
Keywords:
GLUT; Glucose; Intrauterine growth restriction; Placenta; Transport
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