Gestational Diabetes Mellitus Is Associated With Changes in the Concentration and Bioactivity of Placenta-Derived Exosomes in Maternal Circulation Across Gestation

TLDR

Placenta‑derived exosomes are believed to influence pregnancy, yet their exosomal profile in gestational diabetes mellitus remains undefined. The study compared the gestational‑age profile of placenta‑derived exosomes in maternal plasma between GDM and normal pregnancies and evaluated their impact on cytokine release from human umbilical vein endothelial cells. A prospective cohort was sampled at 11–14, 22–24, and 32–36 weeks’ gestation, and a retrospective stratified design quantified exosomes in plasma from 13 normal and 7 GDM pregnancies. Exosome concentration increased throughout pregnancy in both groups, with a significantly greater rise in GDM (≈2.2‑, 1.5‑, and 1.8‑fold higher at each time point), and GDM exosomes stimulated pro‑inflammatory cytokine release from endothelial cells, indicating potential diagnostic utility.

Abstract

Although there is significant interest in elucidating the role of placenta-derived exosomes (PdEs) during pregnancy, the exosomal profile in pregnancies complicated by gestational diabetes mellitus (GDM) remains to be established. The aim of this study was to compare the gestational-age profile of PdEs in maternal plasma of GDM with normal pregnancies and to determine the effect of exosomes on cytokine release from human umbilical vein endothelial cells. A prospective cohort of patients was sampled at three time points during pregnancy for each patient (i.e., 11–14, 22–24, and 32–36 weeks' gestation). A retrospective stratified study design was used to quantify exosomes present in maternal plasma of normal (n = 13) and GDM (n = 7) pregnancies. Gestational age and pregnancy status were identified as significant factors contributing to variation in plasma exosome concentration (ANOVA, P < 0.05). Post hoc analyses established that PdE concentration increased during gestation in both normal and GDM pregnancies; however, the increase was significantly greater in GDM (∼2.2-fold, ∼1.5-fold, and ∼1.8-fold greater at each gestational age compared with normal pregnancies). Exosomes isolated from GDM pregnancies significantly increased the release of proinflammatory cytokines from endothelial cells. Although the role of exosomes during GDM remains to be fully elucidated, exosome profiles may be of diagnostic utility for screening asymptomatic populations.