Lightning Talk & Poster Australasian Extracellular Vesicles Conference 2018

Oxygen tension and low dose aspirin modulates exosomes release and their protein content from placental cells (#52)

Suchismita Dutta 1 , Carlos Palma 1 , Andrew Lai 1 , Dominic Guanzon 1 , Katherin Scholz-Romero 1 , Jonathan Hyett 2 , Sherri Longo 3 , Sathish Kumar 4 , Gregory Rice 1 3 , Carlos Salomon 1 3
  1. The University of Queensland Centre for Clinical Research, Herston, Brisbane City, QLD, Australia
  2. Royal Prince Alfred Hospital Sydney, University of Sydney, Royal Prince Alfred Hospital Sydney, University of Sydney, Sydney, New South Wales, Australia, Sydney, New South Wales, Australia
  3. Maternal-Foetal Medicine, Department of Obstetrics and Gynaecology, Ochsner Clinic Foundation, Maternal-Foetal Medicine, Department of Obstetrics and Gynaecology, Ochsner Clinic Foundation, New Orleans, USA, New Orleans, USA
  4. Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, USA, Wisconsin-Madison, USA

Background

The circulating placental exosomes’ concentration is higher in women with preeclampsia (PE) compared to normal pregnancies. LDA reduces the incidence of PE; however, the effect of LDA on exosomes release from trophoblast cells (TC) has not been established. The aim of this study was to determine the effect of LDA on exosome release and protein content from TCs.

Methods

A syncytiotrophoblast model (ST) was used in the absence or in the presence of Acetylsalicylic  acid (ASA) (0, 0.01, 0.1, 1 and 10 mM) under 1% or 8% O2. Exosomes were isolated by size exclusion chromatography and quantified by nanoparticle tracking analysis.  SWATH mass spectrometry (MS) was used to construct a small ion library from cells and exosomal proteins followed by ingenuity pathway analysis (IPA) to determine signalling pathways and biofunctions.

Results

Hypoxia (i.e. 1% O2) induced the exosome release from ST compared with the values observed from ST cultured under normoxic (i.e. 8% O2) condition. ASA induced exosome release in a concentration dependent-manner at 8% oxygen. However, ASA decreased the exosome release from ST cultured under hypoxic conditions. A total of 640 proteins were identified where α-2 macroglobulin was expressed in STs and their exosomes in different conditions. 

Conclusions

In this study, it was demonstrated that ASA affects the exosome release including its protein content from ST cells; an effect modulated by oxygen tension. Therefore, we hypothesise that ASA prevents the onset of PE through the regulation of placental extracellular exosome release and changes in their protein content.