title: Potential role of cervicovaginal extracellular particles in diagnosis of endometriosis.
abstract: BACKGROUND
  Macaques are an excellent model for many human diseases, including reproductive diseases such as endometriosis. A long-recognized need for early biomarkers of endometriosis has not yet resulted in consensus. While biomarker studies have examined many bodily fluids and targets, cervicovaginal secretions have been relatively under-investigated. Extracellular vesicles (EVs, including exosomes and microvesicles) are found in every biofluid examined, carry cargo including proteins and RNA, and may participate in intercellular signaling. Little is known about EVs in the cervicovaginal compartment, including the effects of reproductive tract disease on quantity and quality of EVs.
  
  
  METHODS
  In September 2014, a 9-year-old rhesus macaque was diagnosed with endometriosis at The Johns Hopkins University School of Medicine. Ultrasound-guided fine needle aspiration of a cyst and subsequent laparotomy confirmed diagnosis. The animal was sent to necropsy following euthanasia for humane reasons. Perimortem vaginal swabs and cervicovaginal lavages were obtained. Using a combination of methods, including ultracentrifugation and NanoSight visualization technology, approximate numbers of EVs from each sample were calculated and compared to populations of EVs from other, reproductively normal macaques. Fewer EVs were recovered from the endometriosis samples as compared with those from reproductively healthy individuals.
  
  
  CONCLUSIONS
  To our knowledge, this is the first examination of EVs in primate cervicovaginal secretions, including those of a macaque with endometriosis. This case study suggests that additional research is justified to determine whether quantification of EVs-or their molecular cargo-in cervicovaginal lavage and vaginal swabs may provide a novel, relatively non-invasive diagnostic for primate endometrial disease or other reproductive tract diseases.
authors.affiliation: Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. Dillon.muth@jhmi.edu.
authors.forename: Dillon C
authors.initials: DC
authors.lastname: Muth
authors.affiliation: Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. mmcalexander14@gmail.com.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: McAlexander
authors.affiliation: Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. lostrenga@gmail.com.
authors.forename: Lauren J
authors.initials: LJ
authors.lastname: Ostrenga
authors.affiliation: Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. npate1@jhmi.edu.
authors.forename: Nathan M
authors.initials: NM
authors.lastname: Pate
authors.affiliation: Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. jizzi1@jhmi.edu.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Izzi
authors.affiliation: Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. rjadams@jhmi.edu.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Adams
authors.affiliation: Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. kpate5@jhmi.edu.
authors.forename: Kelly A Metcalf
authors.initials: KA
authors.lastname: Pate
authors.affiliation: Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. sbeck8@jhmi.edu.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Beck
authors.affiliation: Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. bkarim1@jhmi.edu.
authors.forename: Baktiar O
authors.initials: BO
authors.lastname: Karim
authors.affiliation: Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. kwitwer1@jhmi.edu.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Witwer
mesh_terms: D000818:Animals; D015415:Biomarkers; D004715:Endometriosis / Q000175:diagnosis / Q000473:pathology / Q000662:veterinary*; D000067128:Extracellular Vesicles / Q000502:physiology*; D005260:Female; D008253:Macaca mulatta; D008992:Monkey Diseases / Q000175:diagnosis*
chemical_list: D015415:Biomarkers