Hypoxia-induced changes in the bioactivity of cytotrophoblast-derived exosomes

Salomon, Carlos, Kobayashi, Miharu, Ashman, Keith, Sobrevia, Luis, Mitchell, Murray D. and Rice, Gregory E. (2013) Hypoxia-induced changes in the bioactivity of cytotrophoblast-derived exosomes. PLoS One, 8 11: e79636.1-e79636.14. doi:10.1371/journal.pone.0079636


Author Salomon, Carlos
Kobayashi, Miharu
Ashman, Keith
Sobrevia, Luis
Mitchell, Murray D.
Rice, Gregory E.
Title Hypoxia-induced changes in the bioactivity of cytotrophoblast-derived exosomes
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2013-01-01
Sub-type Article (original research)
DOI 10.1371/journal.pone.0079636
Open Access Status DOI
Volume 8
Issue 11
Start page e79636.1
End page e79636.14
Total pages 14
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Abstract Migration of extravillous trophoblasts (EVT) into decidua and myometrium is a critical process in the conversion of maternal spiral arterioles and establishing placenta perfusion. EVT migration is affected by cell-to-cell communication and oxygen tension. While the release of exosomes from placental cells has been identified as a significant pathway in materno-fetal communication, the role of placental-derived exosomes in placentation has yet to be established. The aim of this study was to establish the effect of oxygen tension on the release and bioactivity of cytotrophoblast (CT)-derived exosomes on EVT invasion and proliferation. CT were isolated from first trimester fetal tissue (n = 12) using a trypsin-deoxyribonuclease-dispase/Percol​lmethod. CT were cultured under 8%, 3% or 1% O2 for 48 h. Exosomes from CT-conditioned media were isolated by differential and buoyant density centrifugation. The effect of oxygen tension on exosome release (µg exosomal protein/106cells/48 h) and bioactivity were established. HTR-8/SVneo (EVT) were used as target cells to establish the effect (bioactivity) of exosomes on invasion and proliferation as assessed by real-time, live-cell imaging (Incucyte™). The release and bioactivity of CT-derived exosomes were inversely correlated with oxygen tension (p<0.001). Under low oxygen tensions (i.e. 1% O2), CT-derived exosomes promoted EVT invasion and proliferation. Proteomic analysis of exosomes identified oxygen-dependent changes in protein content. We propose that in response to changes in oxygen tension, CTs modify the bioactivity of exosomes, thereby, regulating EVT phenotype. Exosomal induction of EVT migration may represent a normal process of placentation and/or an adaptive response to placental hypoxia.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2014 Collection
 
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Citation counts: TR Web of Science Citation Count  Cited 37 times in Thomson Reuters Web of Science Article | Citations
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Created: Tue, 03 Dec 2013, 00:40:47 EST by Roheen Gill on behalf of UQ Centre for Clinical Research