Poster Presentation Australasian Extracellular Vesicles Conference 2018

Glucose Metabolism in Placental Cells is influenced by the Circulating Exosomal miRNA Profile in Gestational Diabetes Mellitus   (#97)

Soumyalekshmi Nair 1 , Nanthini Jayabalan 1 , Dominic Guanzon 1 , Andrew Lai 1 , Katherine Scholz-Romero 1 , Harold David McIntyre 2 , Martha Lappas 3 4 , Carlos Salomon 1
  1. University of Queensland- Centre for Clinical Research (UQCCR), Runcorn, QLD, Australia
  2. Mater Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
  3. Department of Obstetrics and Gynaecology, , University of Melbourne, Melbourne, Victoria, Australia
  4. Mercy Perinatal Research Centre, Mercy Hospital for Women, Melbourne, Victoria, Australia

There is increasing evidence that miRNA, which are enriched in small nanovesicles called exosomes, are important regulators of gene expression. In this study, we tested the hypothesis that circulating exosomes from women with gestational diabetes mellitus (GDM) carry a specific set of miRNAs which regulate genes associated with placental glucose metabolism. Exosomes were isolated from plasma of normal (n=12) and GDM (n=12) pregnancies by differential and buoyant density centrifugation. Exosomal RNA was extracted and a small RNA library was constructed using the Illumina TrueSeq Small RNA kit. Gene target identification and gene ontology analysis for miRNAs was performed using the Ingenuity pathway analysis (IPA). The effect of exosomes on glucose metabolism in placental cells was assessed using a human glucose metabolism array. In plasma, a total of 44 miRNAs were upregulated in exosomes from women with GDM compared to normal pregnant women (p<0.005). IPA showed that exosomal miRNAs isolated from women with GDM regulates the expression of placental genes associated with the glycolytic pathway including 6-phosphofructokinase and phosphopyruvate hydratase. Interestingly, exosomes from women with GDM increases the expression of placental genes associated with glycolysis and decrease the expression of genes associated with pentose phosphate pathway. After integration of the miRNA and mRNA data, we identified 74 differentially expressed exosomal miRNAs associated with the modulation of 10 potential target mRNAs in placental cells, which are associated with glucose metabolism. This data suggests that circulating exosomes under diabetic conditions might modulate the placental metabolic state to enhance glycogen metabolism in GDM.