Lüscher Benjamin P, Marini Camilla, Joerger-Messerli Marianne S, Huang Xiao, Hediger Matthias A, Albrecht Christiane, Baumann Marc U, Surbek Daniel V
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.
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.
Placenta. 2017 Jul;55:94-99. doi: 10.1016/j.placenta.2017.04.023. Epub 2017 Apr 27.
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.
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.
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.
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.
经胎盘的胎儿葡萄糖供应主要受葡萄糖转运蛋白1（GLUT1）调控。GLUT1表达和/或功能的改变可能影响子宫内环境，这可能会损害胎儿发育，并可能导致胎儿编程。迄今为止，尚不清楚胎盘GLUT1是否受子痫前期影响，子痫前期常与宫内生长受限（IUGR）相关。我们探讨了子痫前期导致胎盘GLUT1表达和功能降低这一假说。
收集正常妊娠及子痫前期妊娠后的胎盘。用洗涤后的绒毛组织碎片制备合体滋养层微绒毛（MVM）和基底质膜（BM）微囊泡。采用蛋白质免疫印迹分析和使用Fast SYBR Green的qPCR评估GLUT1蛋白和mRNA表达。使用胎盘来源的合体滋养层微囊泡进行放射性标记葡萄糖摄取试验，以分析GLUT1功能。
与对照组（n = 6）相比，子痫前期（n = 6）合体滋养层（顶端）MVM中GLUT1蛋白表达显著下调（0.40±0.04对1.00±0.06，任意单位，P < 0.001，Student t检验），而GLUT1 mRNA表达无显著差异。此外，合体滋养层微囊泡的功能试验显示，与对照组相比，子痫前期葡萄糖转运活性显著降低（61.78±6.48%，P < 0.05）。BM GLUT1蛋白表达未改变，BM微囊泡的葡萄糖摄取在子痫前期和对照组之间无差异。
我们的研究首次表明，子痫前期胎盘GLUT1在合体滋养层顶端质膜的表达和功能下调。需要进一步研究以评估这些变化是否也在体内发生，并导致子痫前期IUGR的发展。
