title: Syncytin proteins incorporated in placenta exosomes are important for cell uptake and show variation in abundance in serum exosomes from patients with preeclampsia.
abstract: Exosomes are extracellular vesicles that mediate intercellular communication and are involved in several biological processes. The objective of our study was to determine whether endogenous retrovirus group WE, member l (ERVWE1)/syncytin-1 and endogenous retrovirus group FRD, member 1 (ERVFRDE1)/syncytin-2, encoded by human endogenous retrovirus (HERV) envelope (env) genes, are present at the surface of exosomes produced by placenta-derived villous cytotrophoblasts and whether they play a role in cellular uptake of exosomes. In addition, we sought to determine whether these proteins are present in various abundances in serum-derived exosomes from normal pregnant women vs. women with preeclampsia (PE). Isolated exosomes were analyzed for their content by Western blot, a bead-associated flow cytometry approach, and a syncytin-2 ELISA. Binding and uptake were tested through confocal and electron microscopy using the BeWo choriocarcinoma cell line. Quality control of exosome preparations consisted of detection of exosomal and nonexosomal markers. Exosome-cell interactions were compared between cells incubated in the presence of control exosomes, syncytin-1 or syncytin-2-deprived exosomes, or exosomes solely bearing the uncleaved forms of these HERV env proteins. From our data, we conclude that villous cytotrophoblast exosomes are positive for both env proteins and are rapidly taken up by BeWo cells in a syncytin-1- and syncytin-2-dependent manner and that syncytin-2 is reduced in serum-derived exosomes from women with PE when compared to exosomes from normal pregnant women.
authors.affiliation: Département des Sciences Biologiques and Centre de Recherche BioMed, Université du Québec à Montréal, Montreal, Quebec, Canada; and.
authors.forename: Amandine
authors.initials: A
authors.lastname: Vargas
authors.affiliation: Département des Sciences Biologiques and Centre de Recherche BioMed, Université du Québec à Montréal, Montreal, Quebec, Canada; and.
authors.forename: Shufeng
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Département des Sciences Biologiques and Centre de Recherche BioMed, Université du Québec à Montréal, Montreal, Quebec, Canada; and.
authors.forename: Maude
authors.initials: M
authors.lastname: Éthier-Chiasson
authors.affiliation: Département des Sciences Biologiques and Centre de Recherche BioMed, Université du Québec à Montréal, Montreal, Quebec, Canada; and.
authors.forename: Denis
authors.initials: D
authors.lastname: Flipo
authors.affiliation: Département des Sciences Biologiques and Centre de Recherche BioMed, Université du Québec à Montréal, Montreal, Quebec, Canada; and.
authors.forename: Julie
authors.initials: J
authors.lastname: Lafond
authors.affiliation: Centre de Recherche du Centre Hospitalier Universitaire de Québec, Faculty of Medicine, Laval University, Quebec, Quebec, Canada.
authors.forename: Caroline
authors.initials: C
authors.lastname: Gilbert
authors.affiliation: Département des Sciences Biologiques and Centre de Recherche BioMed, Université du Québec à Montréal, Montreal, Quebec, Canada; and barbeau.benoit@uqam.ca.
authors.forename: Benoit
authors.initials: B
authors.lastname: Barbeau
mesh_terms: D000328:Adult; D026962:Amino Acid Transport System ASC / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D002450:Cell Communication; D002459:Cell Fusion; D045744:Cell Line, Tumor; D002822:Choriocarcinoma / Q000473:pathology; D004705:Endocytosis; D020077:Endogenous Retroviruses / Q000235:genetics / Q000502:physiology; D011992:Endosomes / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism*; D005260:Female; D045683:Furin / Q000037:antagonists & inhibitors / Q000502:physiology; D015686:Gene Products, env / Q000097:blood / Q000502:physiology*; D006801:Humans; D018613:Microscopy, Confocal; D015778:Minor Histocompatibility Antigens; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood / Q000172:deficiency / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D027981:Symporters; D014327:Trophoblasts / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D014594:Uterine Neoplasms / Q000473:pathology
chemical_list: D026962:Amino Acid Transport System ASC; C518353:ERVFRD-1 protein, human; D015686:Gene Products, env; C549328:MFSD2A protein, human; D015778:Minor Histocompatibility Antigens; D011257:Pregnancy Proteins; D034741:RNA, Small Interfering; C420506:SLC1A5 protein, human; D027981:Symporters; D025521:Tumor Suppressor Proteins; C405335:syncytin; C468731:FURIN protein, human; D045683:Furin
keywords: HERV; biomarker; fusogenic protein; microvesicles; villous cytotrophoblasts