Circulating Exosomal miRNA Signature in Pregnancies with Gestational Diabetes Mellitus across Gestation

Abstract

Exosomes are small nanovesicles that carry bioactive molecules (e.g., miRNAs) which can be delivered to other cells and modify their phenotype. Recently, we have established that the number of circulating exosomes is higher in women with gestational diabetes mellitus (GDM); however, the exosomal miRNA profile in GDM across gestation has not been established yet. The aim of this study was to establish the circulating exosomal miRNA profile in women with normal glucose tolerance (NGT) and GDM women (BMI-matched) in a prospective cohort of patients at three time points during pregnancy. Exosomal RNA was sequenced using an Illumina NextSeq 500 platform. Linear mixed modelling was performed on the normalized miRNAs across gestation for normal and GDM pregnancies, using the lme4 package in R. Statistically significant differences in miRNA expression between NGT and GDM women was determined using likelihood ratio tests. In the first trimester of pregnancy, 92% (84 out of 92) of exosomal miRNAs were significantly elevated in plasma of women with GDM when compared to NGT women. Interestingly, in the second trimester of pregnancy the expression of these miRNA decreased in the GDM women with no significance difference observed in the exosomal miRNA profile between GDM and NGT women. Gene ontology analysis revealed that miRNAs which changed expression across gestation for GDM pregnancies are involved in the regulation of insulin. In summary, we have identified a range of exosomal miRNAs which change expression across gestation for GDM and normal pregnancies. Gene ontology analysis revealed that these miRNAs are involved in the regulation of insulin, playing significant role in the pathophysiology of GDM. Disclosure D. Guanzon: None. A. Lai: None. K. Scholz-Romero: None. F. Zuñiga: None. E. Diaz: None. H. McIntyre: Speaker's Bureau; Self; Novo Nordisk Inc.. Research Support; Self; Danish Diabetes Academy. M. Lappas: None. C. Salomon: None.