title: Syncytiotrophoblast vesicles show altered micro-RNA and haemoglobin content after ex-vivo perfusion of placentas with haemoglobin to mimic preeclampsia.
abstract: BACKGROUND
  Cell-free foetal haemoglobin (HbF) has been shown to play a role in the pathology of preeclampsia (PE). In the present study, we aimed to further characterize the harmful effects of extracellular free haemoglobin (Hb) on the placenta. In particular, we investigated whether cell-free Hb affects the release of placental syncytiotrophoblast vesicles (STBMs) and their micro-RNA content.
  
  
  METHODS
  The dual ex-vivo perfusion system was used to perfuse isolated cotyledons from human placenta, with medium alone (control) or supplemented with cell-free Hb. Perfusion medium from the maternal side of the placenta was collected at the end of all perfusion phases. The STBMs were isolated using ultra-centrifugation, at 10,000×g and 150,000×g (referred to as 10K and 150K STBMs). The STBMs were characterized using the nanoparticle tracking analysis, identification of surface markers and transmission electron microscopy. RNA was extracted and nine different micro-RNAs, related to hypoxia, PE and Hb synthesis, were selected for analysis by quantitative PCR.
  
  
  RESULTS
  All micro-RNAs investigated were present in the STBMs. Mir-517a, mir-141 and mir-517b were down regulated after Hb perfusion in the 10K STBMs. Furthermore, Hb was shown to be carried by the STBMs.
  
  
  CONCLUSIONS
  This study showed that Hb perfusion can alter the micro-RNA content of released STBMs. Of particular interest is the alteration of two placenta specific micro-RNAs; mir-517a and mir-517b. We have also seen that STBMs may function as carriers of Hb into the maternal circulation.
authors.affiliation: Division of Obstetrics and Gynecology, Department of Clinical Sciences, Lund University Hospital, Lund University, Lund, Sweden.
authors.forename: Tina
authors.initials: T
authors.lastname: Cronqvist
authors.affiliation: Department of Clinical Pharmacology, Ernst Moritz Arndt University of Greifswald, Greifswald, Germany.
authors.forename: Karen
authors.initials: K
authors.lastname: Saljé
authors.affiliation: Department of Zoology, University of Melbourne, Melbourne, Australia.
authors.forename: Mary
authors.initials: M
authors.lastname: Familari
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Seth
authors.initials: S
authors.lastname: Guller
authors.affiliation: Department of Obstetrics and Gynecology, Inselspital, University of Bern, Bern, Switzerland.
authors.forename: Henning
authors.initials: H
authors.lastname: Schneider
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Chris
authors.initials: C
authors.lastname: Gardiner
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Ian L
authors.initials: IL
authors.lastname: Sargent
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Redman
authors.affiliation: Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Matthias
authors.initials: M
authors.lastname: Mörgelin
authors.affiliation: Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Åkerström
authors.affiliation: Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Gram
authors.affiliation: Division of Obstetrics and Gynecology, Department of Clinical Sciences, Lund University Hospital, Lund University, Lund, Sweden.
authors.forename: Stefan R
authors.initials: SR
authors.lastname: Hansson
mesh_terms: D001692:Biological Transport; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D011225:Pre-Eclampsia / Q000235:genetics* / Q000378:metabolism*; D011247:Pregnancy; D022161:Transport Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D014327:Trophoblasts / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D006454:Hemoglobins; D035683:MicroRNAs