Oxygen tension regulates the miRNA profile and bioactivity of exosomes released from extravillous trophoblast cells - liquid biopsies for monitoring complications of pregnancy

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dc.contributor.authorTruong, G.
dc.contributor.authorGuanzon, D.
dc.contributor.authorKinhal, V.
dc.contributor.authorElfeky, O.
dc.contributor.authorLai, A.
dc.contributor.authorLongo, S.
dc.contributor.authorNuzhat, Z.
dc.contributor.authorPalma, C.
dc.contributor.authorScholz-Romero, K.
dc.contributor.authorMenon, R.
dc.contributor.authorMol, B.
dc.contributor.authorRice, G.
dc.contributor.authorSalomon, C.
dc.contributor.editorBouma, G.J.
dc.date.issued2017
dc.description.abstractOur understanding of how cells communicate has undergone a paradigm shift since the recent recognition of the role of exosomes in intercellular signaling. In this study, we investigated whether oxygen tension alters the exosome release and miRNA profile from extravillous trophoblast (EVT) cells, modifying their bioactivity on endothelial cells (EC). Furthermore, we have established the exosomal miRNA profile at early gestation in women who develop pre-eclampsia (PE) and spontaneous preterm birth (SPTB). HTR-8/SVneo cells were used as an EVT model. The effect of oxygen tension (i.e. 8% and 1% oxygen) on exosome release was quantified using nanocrystals (Qdot®) coupled to CD63 by fluorescence NTA. A real-time, live-cell imaging system (Incucyte™) was used to establish the effect of exosomes on EC. Plasma samples were obtained at early gestation (<18 weeks) and classified according to pregnancy outcomes. An Illumina TrueSeq Small RNA kit was used to construct a small RNA library from exosomal RNA obtained from EVT and plasma samples. The number of exosomes was significantly higher in EVT cultured under 1% compared to 8% oxygen. In total, 741 miRNA were identified in exosomes from EVT. Bioinformatic analysis revealed that these miRNA were associated with cell migration and cytokine production. Interestingly, exosomes isolated from EVT cultured at 8% oxygen increased EC migration, whilst exosomes cultured at 1% oxygen decreased EC migration. These changes were inversely proportional to TNF-α released from EC. Finally, we have identified a set of unique miRNAs in exosomes from EVT cultured at 1% oxygen and exosomes isolated from the circulation of mothers at early gestation, who later developed PE and SPTB. We suggest that aberrant exosomal signalling by placental cells is a common aetiological factor in pregnancy complications characterised by incomplete SpA remodeling and is therefore a clinically relevant biomarker of pregnancy complications.
dc.description.statementofresponsibilityGrace Truong, Dominic Guanzon, Vyjayanthi Kinhal, Omar Elfeky, Andrew Lai, Sherri Longo, Zarin Nuzhat, Carlos Palma, Katherin Scholz-Romero, Ramkumar Menon, Ben W. Mol, Gregory E. Rice, Carlos Salomon
dc.identifier.citationPLoS ONE, 2017; 12(3):e0174514-1-e0174514-27
dc.identifier.doi10.1371/journal.pone.0174514
dc.identifier.issn1932-6203
dc.identifier.issn1932-6203
dc.identifier.orcidMol, B. [0000-0001-6887-0262] [0000-0001-8337-550X]
dc.identifier.urihttp://hdl.handle.net/2440/105341
dc.language.isoen
dc.publisherPublic Library of Science
dc.rightsCopyright: © 2017 Truong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.source.urihttps://doi.org/10.1371/journal.pone.0174514
dc.subjectUterus
dc.subjectArteries
dc.subjectChorionic Villi
dc.subjectCells, Cultured
dc.subjectTrophoblasts
dc.subjectHumans
dc.subjectPregnancy Complications
dc.subjectOxygen
dc.subjectMicroRNAs
dc.subjectMicroscopy, Electron, Transmission
dc.subjectBiopsy
dc.subjectBlotting, Western
dc.subjectCluster Analysis
dc.subjectGene Expression Profiling
dc.subjectCell Movement
dc.subjectPregnancy
dc.subjectAdult
dc.subjectFemale
dc.subjectExosomes
dc.subjectHuman Umbilical Vein Endothelial Cells
dc.titleOxygen tension regulates the miRNA profile and bioactivity of exosomes released from extravillous trophoblast cells - liquid biopsies for monitoring complications of pregnancy
dc.typeJournal article
pubs.publication-statusPublished

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