Placental glucose transporter (GLUT)-1 is down-regulated in preeclampsia

Benjamin P Lüscher; Camilla Marini; Marianne S Joerger-Messerli; Xiao Huang; Matthias A Hediger; Christiane Albrecht; Marc U Baumann; Daniel V Surbek

doi:10.1016/j.placenta.2017.04.023

Placental glucose transporter (GLUT)-1 is down-regulated in preeclampsia

Placenta. 2017 Jul:55:94-99. doi: 10.1016/j.placenta.2017.04.023. Epub 2017 Apr 27.

Authors

Benjamin P Lüscher¹, Camilla Marini², Marianne S Joerger-Messerli³, Xiao Huang⁴, Matthias A Hediger⁵, Christiane Albrecht⁶, Marc U Baumann⁷, Daniel V Surbek⁸

Affiliations

¹ Department of Obstetrics and Gynecology, Inselspital, Bern University Hospital, University of Bern, Switzerland; Department of Clinical Research, University of Bern, Switzerland; Swiss National Center of Competence in Research, NCCR TransCure, University of Bern, Bern, Switzerland. Electronic address: Benjamin.luescher@dkf.unibe.ch.
² Department of Obstetrics and Gynecology, Inselspital, Bern University Hospital, University of Bern, Switzerland; Department of Clinical Research, University of Bern, Switzerland; Swiss National Center of Competence in Research, NCCR TransCure, University of Bern, Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences (GCB), University of Bern, Bern, Switzerland. Electronic address: camilla.marini@dkf.unibe.ch.
³ Department of Obstetrics and Gynecology, Inselspital, Bern University Hospital, University of Bern, Switzerland; Department of Clinical Research, University of Bern, Switzerland. Electronic address: marianne.joerger@dkf.unibe.ch.
⁴ Swiss National Center of Competence in Research, NCCR TransCure, University of Bern, Bern, Switzerland; Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland Bühlstrasse 28, CH-3012 Bern, Switzerland. Electronic address: xiao.huang@ibmm.unibe.ch.
⁵ Swiss National Center of Competence in Research, NCCR TransCure, University of Bern, Bern, Switzerland; Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland Bühlstrasse 28, CH-3012 Bern, Switzerland. Electronic address: matthias.hediger@ibmm.unibe.ch.
⁶ Swiss National Center of Competence in Research, NCCR TransCure, University of Bern, Bern, Switzerland; Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland Bühlstrasse 28, CH-3012 Bern, Switzerland. Electronic address: christiane.albrecht@ibmm.unibe.ch.
⁷ Department of Obstetrics and Gynecology, Inselspital, Bern University Hospital, University of Bern, Switzerland; Department of Clinical Research, University of Bern, Switzerland; Swiss National Center of Competence in Research, NCCR TransCure, University of Bern, Bern, Switzerland. Electronic address: marc.baumann@insel.ch.
⁸ Department of Obstetrics and Gynecology, Inselspital, Bern University Hospital, University of Bern, Switzerland; Department of Clinical Research, University of Bern, Switzerland; Swiss National Center of Competence in Research, NCCR TransCure, University of Bern, Bern, Switzerland. Electronic address: daniel.surbek@insel.ch.

PMID: 28623979
DOI: 10.1016/j.placenta.2017.04.023

Abstract

Introduction: Transplacental fetal glucose supply is predominantly regulated by glucose transporter-1 (GLUT1). Altered expression and/or function of GLUT1 may affect the intrauterine environment, which could compromise fetal development and may contribute to fetal programming. To date it is unknown whether placental GLUT1 is affected by preeclampsia, which is often associated with intrauterine growth restriction (IUGR). We addressed the hypothesis that preeclampsia leads to decreased expression and function of placental GLUT1.

Methods: Placentae were obtained following normal pregnancy and from pregnancies affected by preeclampsia. Washed villous tissue fragments were used to prepare syncytial microvillous (MVM) and basal plasma membranes (BM) microvesicles. GLUT1 protein and mRNA expression was assessed by western blot analysis and qPCR using Fast SYBR Green. A radio-labeled glucose up-take assay using placenta-derived syncytial microvesicles was used to analyze GLUT1 function.

Results: GLUT1 protein expression was significantly down-regulated in (apical) MVM of the syncytiotrophoblast in preeclampsia (n = 6) compared to controls (n = 6) (0.40 ± 0.04 versus 1.00 ± 0.06, arbitrary units, P < 0.001, Student's t-test), while GLUT1 mRNA expression did not show a significant difference. In addition, the functional assay in syncytial microvesicles showed a significantly decreased glucose transport activity in preeclampsia (61.78 ± 6.48%, P < 0.05) compared to controls. BM GLUT1 protein expression was unchanged and glucose up-take into BM microvesicles showed no differences between the preeclampsia and control groups.

Discussion: Our study shows for the first time that in preeclampsia placental GLUT1 expression and function are down-regulated at the apical plasma membrane of the syncytiotrophoblast. Further studies are needed to assess whether these changes occur also in vivo and contribute to the development of IUGR in preeclampsia.

Keywords: GLUT1; Glucose transport; Placenta; Preeclampsia; Syncytiotrophoblast.

MeSH terms

Adult
Case-Control Studies
Cell Membrane / metabolism
Down-Regulation
Female
Glucose Transporter Type 1 / metabolism*
Humans
Placenta / metabolism*
Pre-Eclampsia / metabolism*
Pregnancy

Substances

Glucose Transporter Type 1