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

Diabetes. 2016 Mar;65(3):598-609. doi: 10.2337/db15-0966. Epub 2015 Dec 30.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Case-Control Studies
  • Cytokines / metabolism*
  • Diabetes, Gestational / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Exosomes / metabolism*
  • Female
  • Gestational Age
  • Glucose Tolerance Test
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Human Umbilical Vein Endothelial Cells / metabolism*
  • Humans
  • Infant, Newborn
  • Inflammation
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-2 / metabolism
  • Interleukin-4 / metabolism
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Male
  • Placenta / metabolism*
  • Pregnancy
  • Pregnancy Trimester, Second
  • Pregnancy Trimester, Third
  • Pulsatile Flow
  • ROC Curve
  • Tumor Necrosis Factor-alpha / metabolism
  • Ultrasonography, Doppler
  • Uterine Artery / diagnostic imaging
  • Young Adult


  • CXCL8 protein, human
  • Cytokines
  • IL10 protein, human
  • IL2 protein, human
  • IL4 protein, human
  • IL6 protein, human
  • Interleukin-2
  • Interleukin-6
  • Interleukin-8
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor