title: Intrauterine Candida albicans infection elicits severe inflammation in fetal sheep.
abstract: BACKGROUND
  Preventing preterm birth and subsequent adverse neonatal sequelae is among the greatest clinical challenges of our time. Recent studies suggest a role for Candida spp. in preterm birth and fetal injury, as a result of their colonization of either the vagina and/or the amniotic cavity. We hypothesized that intraamniotic Candida albicans would cause a vigorous, acute fetal inflammatory response.
  
  
  METHODS
  Sheep carrying singleton pregnancies received single intraamniotic injections of either saline (control) or 10(7) colony-forming units C. albicans 1 or 2 d prior to surgical delivery and euthanasia at 124 ± 2 d gestation.
  
  
  RESULTS
  Colonization of the amniotic cavity by C. albicans resulted in a modest inflammatory response at 1 d and florid inflammation at 2 d, characterized by fetal thrombocytopenia, lymphopenia, and significant increases of inflammatory cytokines/chemokines in the fetal membranes skin, lung, and the amniotic fluid.
  
  
  CONCLUSIONS
  Acute colonization of the amniotic cavity by C. albicans causes severe intrauterine inflammation and fetal injury. C. albicans is a potent fetal pathogen that can contribute to adverse pregnancy outcomes.
authors.affiliation: School of Women's and Infants' Health, The University of Western Australia, Perth, Australia.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Payne
authors.affiliation: School of Women's and Infants' Health, The University of Western Australia, Perth, Australia.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Kemp
authors.affiliation: 1] School of Women's and Infants' Health, The University of Western Australia, Perth, Australia [2] Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati School of Medicine, Cincinnati, Ohio.
authors.forename: Suhas G
authors.initials: SG
authors.lastname: Kallapur
authors.affiliation: Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati School of Medicine, Cincinnati, Ohio.
authors.forename: Paranthaman Senthamarai
authors.initials: PS
authors.lastname: Kannan
authors.affiliation: 1] School of Women's and Infants' Health, The University of Western Australia, Perth, Australia [2] Division of Perinatal Medicine, Tohoku University Hospital, Sendai, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Saito
authors.affiliation: 1] School of Women's and Infants' Health, The University of Western Australia, Perth, Australia [2] Division of Perinatal Medicine, Tohoku University Hospital, Sendai, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Miura
authors.affiliation: School of Women's and Infants' Health, The University of Western Australia, Perth, Australia.
authors.forename: John P
authors.initials: JP
authors.lastname: Newnham
authors.affiliation: 1] School of Women's and Infants' Health, The University of Western Australia, Perth, Australia [2] MRC Centre for Reproductive Health, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Stock
authors.affiliation: School of Women's and Infants' Health, The University of Western Australia, Perth, Australia.
authors.forename: Demelza J
authors.initials: DJ
authors.lastname: Ireland
authors.affiliation: 1] School of Women's and Infants' Health, The University of Western Australia, Perth, Australia [2] Department of Paediatrics, School of Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Boris W
authors.initials: BW
authors.lastname: Kramer
authors.affiliation: 1] School of Women's and Infants' Health, The University of Western Australia, Perth, Australia [2] Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati School of Medicine, Cincinnati, Ohio.
authors.forename: Alan H
authors.initials: AH
authors.lastname: Jobe
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002176:Candida albicans; D002177:Candidiasis / Q000503:physiopathology / Q000662:veterinary*; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005333:Fetus / Q000378:metabolism / Q000382:microbiology*; D006854:Hydrocortisone / Q000097:blood; D007249:Inflammation / Q000503:physiopathology*; D008168:Lung / Q000473:pathology; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D012756:Sheep; D012757:Sheep Diseases / Q000382:microbiology* / Q000503:physiopathology*; D012867:Skin / Q000473:pathology; D014599:Uterus / Q000382:microbiology / Q000503:physiopathology*
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D006854:Hydrocortisone