Extracellular vesicles and their role in gestational diabetes mellitus

Abstract

Gestational diabetes mellitus (GDM) is a complex disorder that is defined by glucose intolerance with onset during pregnancy. The incidence of GDM is increasing worldwide. Pregnancies complicated with GDM have higher rates of maternal and fetal morbidity with short- and long-term consequences, including increased rates of cardiovascular disease and type II diabetes for both the mother and offspring. The pathophysiology of GDM still remains unclear and there has been interest in the role of small extracellular vesicles (sEVs) in the maternal metabolic adaptations that occur in pregnancy and GDM. Small EVs are nanosized particles that contain bioactive content, including miRNAs and proteins, which are released by cells to provide cell-to-cell communication. Pregnancy induces an increase in total and placental-secreted sEVs across gestation, with a further increase in sEV number and changes in the protein and miRNA composition of these sEVs in GDM. Research has suggested that these sEVs have an impact on maternal adaptations during pregnancy, including targeting the pancreas, skeletal muscle and adipose tissue. Consequently, this review will focus on the differences in total and placental sEVs in GDM compared to normal pregnancy, the role of sEVs in the pathophysiology of GDM and their clinical application as potential GDM biomarkers.

Keywords: Exosomes; Extracellular vesicles; Gestational diabetes mellitus; Microvesicles; Placenta; Pregnancy; Proteins; miRNAs.

Fig. 1.

Schematic diagram of the release and actions of small extracellular vesicles (sEVs) in gestational diabetes mellitus (GDM) during pregnancy. In GDM there is an increase in the concentration of total and placental sEVs in the maternal circulation across gestation. The release of sEVs during pregnancy leads to communication between the maternal and fetal systems via the placenta. In GDM, sEVs have been shown to play a role in the pathogenesis of GDM by targeting adipose tissue, skeletal muscle and the pancreas in the maternal system.