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Single extracellular vesicle analysis in human amniotic fluid shows evidence of phenotype alterations in preeclampsia

Natalia Gebara, Julia Scheel, Renata Skovronova, Cristina Grange, Luca Marozio, Shailendra Gupta, Veronica Giorgione, Federico Caicci, Chiara Benedetto, Asma Khalil, Benedetta Bussolati
doi: https://doi.org/10.1101/2022.02.14.480331
Natalia Gebara
1Department of Molecular Biotechnology and Health Sciences, University of Turin, Italy
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Julia Scheel
2Department of Systems Biology and Bioinformatics, University of Rostock, Germany
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Renata Skovronova
1Department of Molecular Biotechnology and Health Sciences, University of Turin, Italy
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Cristina Grange
3Department of Medical Sciences, University of Turin, Turin, Italy
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Luca Marozio
4Department of Surgical Sciences, Obstetrics and Gynecology, University of Turin, Italy
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Shailendra Gupta
2Department of Systems Biology and Bioinformatics, University of Rostock, Germany
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Veronica Giorgione
5Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George’s University of London, UK
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Federico Caicci
6DiBio Imaging facility, University of Padua, Italy
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Chiara Benedetto
4Department of Surgical Sciences, Obstetrics and Gynecology, University of Turin, Italy
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Asma Khalil
5Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George’s University of London, UK
7Fetal Medicine Unit, St George’s University Hospitals NHS Foundation Trust, St George’s University of London, UK
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Benedetta Bussolati
1Department of Molecular Biotechnology and Health Sciences, University of Turin, Italy
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  • For correspondence: benedetta.bussolati@unito.it
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Abstract

Amniotic fluid surrounding the developing fetus is a complex biological fluid rich in metabolically active bio-factors. The presence of extracellular vesicles (EVs) in amniotic fluid has been mainly related to fetal urine. We here characterized EVs from term amniotic fluid in terms of surface marker expression using different orthogonal techniques. EVs appeared to be a heterogeneous population expressing markers of renal, placental, epithelial and stem cells. Moreover, we compared amniotic fluid EVs from normal pregnancies with those of preeclampsia, a hypertensive disorder affecting up to 8% of pregnancies worldwide. An increase of CD105 (endoglin) expressing EVs was observed in preeclamptic amniotic fluid by bead-based cytofluorimetric analysis, and further confirmed using a chip-based analysis. HLA-G, a typical placental marker, was not co-expressed by the majority of CD105+ EVs, suggesting their origin from amniotic fluid cells. At a functional level, preeclampsia-derived EVs, but not normal pregnancy EVs, showed an antiangiogenic effect, possibly due to the decoy effect of endoglin. In addition, several miRNAs were differentially expressed in preeclampsia-derived EVs and directly related to the modulation of angiogenesis and trophoblast function. Our results provide a characterization of term amniotic fluid-EVs, supporting their origin from fetal and placental cells. In preeclampsia, the observed antiangiogenic characteristics of amniotic fluid-EVs may reflect the hypoxic and antiangiogenic microenvironment and could possibly impact on the developing fetus or on the surrounding fetal membranes.

  • extracellular vesicles
  • exosomes
  • amniotic fluid
  • placenta
  • pregnancy disorders
  • angiogenesis
  • soluble endoglin

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Disclosure: The authors declare no conflict of interest.

  • Funding: NG, JS and VG are part of the iPLACENTA and RS of RenalToolBox projects, which have received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No. 765274 and No. 813839 respectively.

  • https://fairdomhub.org/projects/244

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted February 14, 2022.
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Single extracellular vesicle analysis in human amniotic fluid shows evidence of phenotype alterations in preeclampsia
Natalia Gebara, Julia Scheel, Renata Skovronova, Cristina Grange, Luca Marozio, Shailendra Gupta, Veronica Giorgione, Federico Caicci, Chiara Benedetto, Asma Khalil, Benedetta Bussolati
bioRxiv 2022.02.14.480331; doi: https://doi.org/10.1101/2022.02.14.480331
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Single extracellular vesicle analysis in human amniotic fluid shows evidence of phenotype alterations in preeclampsia
Natalia Gebara, Julia Scheel, Renata Skovronova, Cristina Grange, Luca Marozio, Shailendra Gupta, Veronica Giorgione, Federico Caicci, Chiara Benedetto, Asma Khalil, Benedetta Bussolati
bioRxiv 2022.02.14.480331; doi: https://doi.org/10.1101/2022.02.14.480331

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