A gestational profile of placental exosomes in maternal plasma and their effects on endothelial cell migration

PLoS One. 2014 Jun 6;9(6):e98667. doi: 10.1371/journal.pone.0098667. eCollection 2014.

Abstract

Studies completed to date provide persuasive evidence that placental cell-derived exosomes play a significant role in intercellular communication pathways that potentially contribute to placentation and development of materno-fetal vascular circulation. The aim of this study was to establish the gestational-age release profile and bioactivity of placental cell-derived exosome in maternal plasma. Plasma samples (n = 20 per pregnant group) were obtained from non-pregnant and pregnant women in the first (FT, 6-12 weeks), second (ST, 22-24 weeks) and third (TT, 32-38 weeks) trimester. The number of exosomes and placental exosome contribution were determined by quantifying immunoreactive exosomal CD63 and placenta-specific marker (PLAP), respectively. The effect of exosomes isolated from FT, ST and TT on endothelial cell migration were established using a real-time, live-cell imaging system (Incucyte). Exosome plasma concentration was more than 50-fold greater in pregnant women than in non-pregnant women (p<0.001). During normal healthy pregnancy, the number of exosomes present in maternal plasma increased significantly with gestational age by more that two-fold (p<0.001). Exosomes isolated from FT, ST and TT increased endothelial cell migration by 1.9±0.1, 1.6±0.2 and 1.3±0.1-fold, respectively compared to the control. Pregnancy is associated with a dramatic increase in the number of exosomes present in plasma and maternal plasma exosomes are bioactive. While the role of placental cell-derived exosome in regulating maternal and/or fetal vascular responses remains to be elucidated, changes in exosome profile may be of clinical utility in the diagnosis of placental dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / metabolism
  • Cell Movement*
  • Endothelial Cells / cytology*
  • Exosomes / metabolism*
  • Female
  • Gestational Age
  • Humans
  • Male
  • Mothers*
  • Placenta / cytology*
  • Plasma / cytology*
  • Pregnancy

Substances

  • Biomarkers

Grant support

This investigation was supported by CONICYT (ACT-73 PIA, Pasantía Doctoral en el Extranjero BECAS Chile), FONDECYT (1110977). CS hold CONICYT-PhD fellowships and Faculty of Medicine/PUC-PhD fellowships. CS holds a Postdoctoral Fellowship at The University of Queensland Centre for Clinical Research, Brisbane, Australia. GER was in receipt of an NHMRC Principal Research Fellowship. The work described herein was partially funded by a CIEF grant (University of Queensland), a Smart Futures Fund grant (Department of Employment, Economic Development and Innovation, Queensland Government) and a Translating Health Discovery into Clinical Applications SuperScience Award (Department of Industry, Innovation, Science, Research and Tertiary Education, Australian Government). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.