The link between metabolic disorders during pregnancy and high risk of developing chronic noncommunicable diseases in later life has been well established. However, why the fetuses exposed to GDM have a higher risk of abnormal glucose homeostasis in later life, is still not fully understood. Exosomes have been well characterised in maternal circulation in normal and gestational diabetes pregnancies, however, the little is known about the profile of exosomes in fetal circulation. In this study, we isolated exosomes from cord-blood from women with normal tolerance glucose (NGT, n=35) and GDM (n=40) at the time of delivery. The miRNA content of exosomes was determined using a small RNA sequencing. The levels of circulating exosomes were significantly higher in GDM compared to NGT (p<0.05). Linear regression analysis identified a positive association between fetal length, maternal BMI and the levels of circulating exosomes in GDM, while no significant association was observed for NGT. Analysis of the miRNA within exosomes identified a range of miRNAs differentially expressed between NGT and GDM samples. Principal component analysis reveals a separation of the groups based on their miRNA profile. The miRNA contributing the most to this separation between normal and GDM conditions is miR-22-3p, thus this miRNA may be a key candidate for future GDM diagnostic strategies. Gene Ontology analysis shows that the miRNAs identified in exosomes regulate genes involved in insulin secretion in response to glucose stimulus, insulin receptor signalling, and glucose homeostasis. Thus, these data suggest that exosomes may alter gene expression and ultimately the cell phenotype by transferring specific miRNAs to target cells.
V. Ormazabal: None. S. Nair: None. D. Guanzon: None. F. Zuniga: None. D. McIntyre: Other Relationship; Self; Novo Nordisk A/S. M. Lappas: None. C. Salomon: None.
Diabetes Australia; Fondo Nacional de Desarrollo Científico y Tecnológico (1170809, 1190522)