title: The Effect of Glucose on the Release and Bioactivity of Exosomes From First Trimester Trophoblast Cells.
abstract: BACKGROUND
  Hyperglycemia and hypoxia are risk factors of metabolic complication during pregnancy. The interactions between oxygen and glucose-sensing pathways that regulate exosome bioactivity from placental cells, however, have not been established.
  
  
  OBJECTIVE
  The aim of this study was to test the hypothesis that exosomal signaling by placental cells (defined as the number of exosomes released per unit time and their bioactivity) is responsive to extracellular glucose concentration.
  
  
  METHODS
  First-trimester primary trophoblast cells were incubated with D-glucose (5 mM or 25 mM) under 1%, 3%, or 8% O2 for 48 hours. Exosomes were isolated from cell-conditioned media by differential and buoyant density centrifugation. The total number of exosome vesicles was determined by quantifying immunoreactive exosomal CD63. The effect of exosomes on cytokine (granulocyte macrophage colony-stimulating factor, IL-2, IL-4, IL-6. IL-8, IL-10, interferon-γ, and TNF-α) release from endothelial cells was established by a protein solution array analysis.
  
  
  RESULTS
  Glucose (25 mM) significantly increased the release of exosomes from trophoblast cells at all oxygen tensions tested (by approximately 2-fold when compared with controls, P < .001). Exosomes (100 μg/mL exosomal protein) released from trophoblast cells significantly increased (P < .05) the release of all cytokines from human umbilical vein endothelial cells when compared with the control (ie, cells without exosomes), with the exception of IL-2 and IL-10 (P > .05).
  
  
  CONCLUSIONS
  The effects of high glucose on exosomes bioactivity may be recapitulated in vivo and is of clinical relevance in association with maternal insulin resistance (resulting in hyperglycemia) and preeclampsia (associated with placental insufficiency and hypoxia).
authors.affiliation: Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, Brisbane 4029, Queensland, Australia.
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Rice
authors.affiliation: Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, Brisbane 4029, Queensland, Australia.
authors.forename: Katherin
authors.initials: K
authors.lastname: Scholz-Romero
authors.affiliation: Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, Brisbane 4029, Queensland, Australia.
authors.forename: Emma
authors.initials: E
authors.lastname: Sweeney
authors.affiliation: Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, Brisbane 4029, Queensland, Australia.
authors.forename: Hassendrini
authors.initials: H
authors.lastname: Peiris
authors.affiliation: Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, Brisbane 4029, Queensland, Australia.
authors.forename: Miharu
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, Brisbane 4029, Queensland, Australia.
authors.forename: Gregory
authors.initials: G
authors.lastname: Duncombe
authors.affiliation: Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, Brisbane 4029, Queensland, Australia.
authors.forename: Murray D
authors.initials: MD
authors.lastname: Mitchell
authors.affiliation: Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, Brisbane 4029, Queensland, Australia.
authors.forename: Carlos
authors.initials: C
authors.lastname: Salomon
mesh_terms: D016207:Cytokines / Q000378:metabolism; D055354:Exosomes / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000378:metabolism*; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism
chemical_list: D016207:Cytokines; D005947:Glucose