miRNA Profiles in Extracellular Vesicles From Serum Early in Pregnancies Complicated by Gestational Diabetes Mellitus

Context: Underlying mechanisms leading to gestational diabetes mellitus (GDM) are still under investigation, and it is unclear whether the placenta plays a role in triggering glucose intolerance or if its functions are modified in response to the hyperglycemia. Circulating miRNAs are involved in placental development and function and are encapsulated in extracellular vesicles (EVs). Objective: To compare differential expression of miRNAs in circulating EVs in pregnancies complicated by GDM vs controls. Methods: This was a case-control study nested in a prospective pregnancy cohort including 23 women with GDM and 46 matched controls. The presence of serum EVs in early pregnancy was validated by transmission electron microscopy. Placental dimensions were assessed at 11 to 13 weeks of gestation. Differential expression of 17 miRNAs encapsulated in EVs (miR-122-5p, miR-132-3p, miR-1323, miR-182-3p, miR-210-3p, miR-29a-3p, miR-29b-3p, miR-342-3p, miR-517-5p, miR-517a-3p, miR-518b, miR-520h, miR-525-5p, miR-136-5p, miR-342-3p, miR-376c-5p, and miR-494-3p) was assessed using quantitative reverse transcription PCR. Results: EVs were present in the early phase of placentation (6 to 15 weeks of gestation) in both cases and controls. No differences were observed for placental dimensions and estimated placental volume between GDM and control groups. Ten miRNAs (miR-122-5p; miR-132-3p; miR-1323; miR-136-5p; miR-182-3p; miR-210-3p; miR-29a-3p; miR-29b-3p; miR-342-3p, and miR-520h) showed significantly higher levels in GDM cases than in controls (P <= 0.05). Bioinformatics analysis showed that these miRNAs are involved in trophoblast proliferation/differentiation as well as in insulin secretion/regulation and glucose transport in pregnant women. Conclusion: The miRNA content of blood EVs may be a promising avenue for studying the early effect of impaired glucose metabolism on placental development.