title: Genital Injury Signatures and Microbiome Alterations Associated With Depot Medroxyprogesterone Acetate Usage and Intravaginal Drying Practices.
abstract: Increasing evidence suggests depot medroxyprogesterone acetate (DMPA) and intravaginal practices may be associated with human immunodeficiency virus (HIV-1) infection risk; however, the mechanisms are not fully understood. This study evaluated the effect of DMPA and intravaginal practices on the genital proteome and microbiome to gain mechanistic insights.
  
  
  
  Cervicovaginal secretions from 86 Kenyan women, including self-reported DMPA users (n = 23), nonhormonal contraceptive users (n = 63), and women who practice vaginal drying (n = 46), were analyzed using tandem-mass spectrometry.
  
  
  
  We identified 473 human and 486 bacterial proteins from 18 different genera. Depot medroxyprogesterone acetate use associated with increased hemoglobin and immune activation (HBD, HBB, IL36G), and decreased epithelial repair proteins (TFF3, F11R). Vaginal drying associated with increased hemoglobin and decreased phagocytosis factors (AZU1, MYH9, PLAUR). Injury signatures were exacerbated in DMPA users who also practiced vaginal drying. More diverse (H index: 0.71 vs 0.45; P = .009) bacterial communities containing Gardnerella vaginalis associated with vaginal drying, whereas DMPA showed no significant association with community composition or diversity.
  
  
  
  These findings provide new insights into the impact of DMPA and vaginal drying on mucosal barriers. Future investigations are needed to confirm their relationship with HIV risk in women.
authors.affiliation: National HIV and Retrovirology Labs, JC Wilt Infectious Disease Research Centre, Public Health Agency of Canada, Winnipeg, Manitoba, Canada|Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada.
authors.forename: Kenzie D
authors.initials: KD
authors.lastname: Birse
authors.affiliation: National HIV and Retrovirology Labs, JC Wilt Infectious Disease Research Centre, Public Health Agency of Canada, Winnipeg, Manitoba, Canada|Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Romas
authors.affiliation: Departments of Global Health and Epidemiology, University of Washington, Seattle, Washington, USA.
authors.forename: Brandon L
authors.initials: BL
authors.lastname: Guthrie
authors.affiliation: Affinity Proteomics, SciLife Lab, School of Biotechnology, KTH-Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Nilsson
authors.affiliation: Kenya Medical Research Institute, Nairobi, Kenya
authors.forename: Rose
authors.initials: R
authors.lastname: Bosire
authors.affiliation: Department of Obstetrics and Gynecology, University of Nairobi, Kenya.
authors.forename: James
authors.initials: J
authors.lastname: Kiarie
authors.affiliation: Department of Medicine, University of Washington, Seattle, USA.
authors.forename: Carey
authors.initials: C
authors.lastname: Farquhar
authors.affiliation: Department of Medicine, Solna, Unit of Infectious Diseases, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Broliden
authors.affiliation: National HIV and Retrovirology Labs, JC Wilt Infectious Disease Research Centre, Public Health Agency of Canada, Winnipeg, Manitoba, Canada|Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada.|Department of Medicine, Solna, Unit of Infectious Diseases, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Adam D
authors.initials: AD
authors.lastname: Burgener
mesh_terms: D000328:Adult; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D003271:Contraceptive Agents, Female / Q000008:administration & dosage* / Q000009:adverse effects; D003430:Cross-Sectional Studies; D003890:Desiccation; D005260:Female; D006194:Gardnerella vaginalis / Q000187:drug effects / Q000302:isolation & purification; D006678:HIV / Q000302:isolation & purification; D015658:HIV Infections / Q000453:epidemiology*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D007630:Kenya; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage* / Q000009:adverse effects; D064307:Microbiota; D020409:Molecular Motor Proteins / Q000235:genetics / Q000378:metabolism; D009092:Mucous Membrane / Q000187:drug effects / Q000382:microbiology; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D000071165:Trefoil Factor-3 / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D014621:Vagina / Q000293:injuries / Q000382:microbiology*; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D003271:Contraceptive Agents, Female; C407243:F11R protein, human; D006454:Hemoglobins; C508589:IL36G protein, human; D007375:Interleukin-1; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; C410333:TACC2 protein, human; C082495:TFF3 protein, human; D000071165:Trefoil Factor-3; D025521:Tumor Suppressor Proteins; D017258:Medroxyprogesterone Acetate; D018995:Myosin Heavy Chains
keywords: DMPA; Depot medroxyprogesterone acetate; HIV; Mucosa; genital injury; metaproteome; microbiome; progestin; proteomics; vaginal drying