Glucose transporter isoform 4 is expressed in the syncytiotrophoblast of first trimester human placenta

Background: Placental glucose transport mechanisms in early pregnancy are poorly understood. The aims of this study were to investigate the expression of glucose transporter (GLUT) isoforms 1, 3 and 4 in first trimester villous tissue, to assess the effects of insulin on glucose uptake and compare them with term. Methods: The expression of GLUT isoforms was investigated using immunohistochemistry, Western blot and reverse transcription (RT)-PCR in trophoblast tissue from terminations at 6-13 weeks gestation and term. The effects of insulin (300 ng/ml, 1 h) on glucose uptake were studied in villous fragments. Results: In the first trimester, GLUT1 and GLUT3 were present in the microvillous membrane and the cytotrophoblast, and GLUT4 in perinuclear membranes in the cytosol of the syncytiotrophoblast (ST). GLUT4 protein (48 kDa) and mRNA were identified in trophoblast homogenates. Whereas GLUT1 was expressed abundantly in term placenta, the expression of GLUT3 and 4 was markedly lower at term compared with first trimester. Insulin increased glucose uptake by 182% (n=6, P<0.05) in first trimester fragments, but not in term fragments. Conclusions: The insulin-regulatable GLUT4 is expressed in the cytosol of first trimester ST compatible with a role for GLUT4 in placental glucose transport in early pregnancy. The placental expression pattern of GLUT isoforms in early pregnancy is distinct from that later in pregnancy.