Oral extracellular vesicles in early pregnancy can identify patients at risk of developing gestational diabetes mellitus

PLoS One. 2019 Jun 26;14(6):e0218616. doi: 10.1371/journal.pone.0218616. eCollection 2019.

Abstract

Aim: To isolate and characterize oral extracellular vesicles from gingival crevicular fluid at 11-14 weeks and evaluate their capacity to identify patients at risk of developing gestational diabetes mellitus.

Methods: A case-control study was conducted, including patients who developed gestational diabetes mellitus (n = 11) and healthy pregnant controls (n = 23). Obstetric and periodontal histories were recorded at 11-14 weeks of gestation, and samples of gingival crevicular fluid obtained. Extracellular vesicles were isolated from gingival crevicular fluid by ExoQuick. Nanoparticle tracking analysis, ELISA and transmission electron microscopy were used to characterize extracellular vesicles.

Results: Total extracellular vesicles isolated from gingival crevicular fluid were significantly higher in patients who developed gestational diabetes mellitus later in pregnancy compared to normoglycemic pregnant women (6.3x109 vs 1.7 x1010, p value = 0.0026), and the concentration of the extracellular vesicles delivered an area under the ROC curve of 0.81. The distribution size of extracellular vesicles obtained using ExoQuick was around 148 ± 57 nm. There were no significant differences in the periodontal status between cases and controls. The exosome transmembrane protein CD63 was also detected in the extracellular vesicles of gingival crevicular fluid.

Conclusion: We were able to isolate extracellular vesicles from gingival crevicular fluid using a method that is suitable to be applied in a clinical setting. Our results provide an insight into the potential capacity of first trimester oral extracellular vesicles as early biomarkers for the prediction of gestational diabetes mellitus in pre-symptomatic women.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Diabetes, Gestational / diagnosis
  • Diabetes, Gestational / etiology*
  • Diabetes, Gestational / metabolism
  • Extracellular Vesicles / metabolism
  • Extracellular Vesicles / ultrastructure*
  • Female
  • Gingival Crevicular Fluid / cytology*
  • Gingival Crevicular Fluid / metabolism
  • Humans
  • Liquid Biopsy / methods
  • Particle Size
  • Periodontitis / complications
  • Periodontitis / metabolism
  • Periodontitis / pathology
  • Pregnancy
  • Pregnancy Trimester, First
  • Retrospective Studies
  • Risk Factors
  • Tetraspanin 30 / metabolism

Substances

  • CD63 protein, human
  • Tetraspanin 30

Grants and funding

AC and SEI were supported by FONDEF IDeA [ID16I10452] (https://www.conicyt.cl/fondef/) RR was supported, in part, by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (NICHD/NIH) (https://www.nichd.nih.gov/); and, in part, with Federal funds from NICHD, NIH under Contract No. HSN275201300006C (https://www.nichd.nih.gov/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.