Introduction: Gestational diabetes mellitus (GDM) is a serious health issue affecting 9-15% of all pregnancies worldwide. Recently, it has been suggested that circulating exosomes present in maternal blood play a role in normal pregnancies, as well as in complications which arise during pregnancy. Exosomes carry specific molecules including miRNAs, which can be delivered to other cells and modify their biological function. Interestingly, elevated levels of circulating exosomes in GDM have been previously described. However, changes in their miRNA content in GDM across gestation has not been established.
Methods: Plasma derived exosomes were isolated using differential centrifugation, from normal glucose tolerant (NGT) and GDM pregnant women at three time points during pregnancy. Next generation sequencing (NextSeq 500) was used to profile small RNAs from these plasma exosomes. Linear mixed modelling was performed on normalized miRNAs across gestation for NGT and GDM pregnancies, using the lme4 R package. Statistically significant differences in miRNA expression across gestation and between normal and GDM pregnancies was determined using likelihood ratio tests.
Results: A total of 279 (NGT), 308 (GDM) and 175 (NGT vs GDM) statistically significant miRNAs were identified to change expression across gestation. Gene ontology analysis revealed that miRNAs with altered expression across gestation in GDM pregnancies are involved in the regulation of glucose metabolism and insulin signalling.
Conclusions: This study provides evidence that the miRNA content changes across gestation in GDM compared to NGT, suggesting that the delivery of bioactive miRNAs via exosomes could potentially be involved in maternal metabolic adaptation to pregnancy.