title: Trophoblast expression of the minor histocompatibility antigen HA-1 is regulated by oxygen and is increased in placentas from preeclamptic women.
abstract: BACKGROUND
  Maternal T-cells reactive towards paternally inherited fetal minor histocompatibility antigens are expanded during pregnancy. Placental trophoblast cells express at least four fetal antigens, including human minor histocompatibility antigen 1 (HA-1). We investigated oxygen as a potential regulator of HA-1 and whether HA-1 expression is altered in preeclamptic placentas.
  
  
  METHODS
  Expression and regulation of HA-1 mRNA and protein were examined by qRT-PCR and immunohistochemistry, using first, second, and third trimester placentas, first trimester placental explant cultures, and term purified cytotrophoblast cells. Low oxygen conditions were achieved by varying ambient oxygen, and were mimicked using cobalt chloride. HA-1 mRNA and protein expression levels were evaluated in preeclamptic and control placentas.
  
  
  RESULTS
  HA-1 protein expression was higher in the syncytiotrophoblast of first trimester as compared to second trimester and term placentas (P<0.01). HA-1 mRNA was increased in cobalt chloride-treated placental explants and purified cytotrophoblast cells (P = 0.04 and P<0.01, respectively) and in purified cytotrophoblast cells cultured under 2% as compared to 8% and 21% oxygen (P<0.01). HA-1 mRNA expression in preeclamptic vs. control placentas was increased 3.3-fold (P = 0.015). HA-1 protein expression was increased in syncytial nuclear aggregates and the syncytiotrophoblast of preeclamptic vs. control placentas (P = 0.02 and 0.03, respectively).
  
  
  CONCLUSIONS
  Placental HA-1 expression is regulated by oxygen and is increased in the syncytial nuclear aggregates and syncytiotrophoblast of preeclamptic as compared to control placentas. Increased HA-1 expression, combined with increased preeclamptic syncytiotrophoblast deportation, provides a novel potential mechanism for exposure of the maternal immune system to increased fetal antigenic load during preeclampsia.
authors.affiliation: Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: C
authors.initials: C
authors.lastname: Linscheid
authors.affiliation: Saint Luke's Health System, Department of Maternal and Fetal Medicine, Kansas City, MO, USA.
authors.forename: E
authors.initials: E
authors.lastname: Heitmann
authors.affiliation: Saint Luke's Health System, Department of Maternal and Fetal Medicine, Kansas City, MO, USA.
authors.forename: P
authors.initials: P
authors.lastname: Singh
authors.affiliation: Saint Luke's Health System, Department of Maternal and Fetal Medicine, Kansas City, MO, USA.
authors.forename: E
authors.initials: E
authors.lastname: Wickstrom
authors.affiliation: Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: L
authors.initials: L
authors.lastname: Qiu
authors.affiliation: The Center for Women's Health, Overland Park, KS, USA.
authors.forename: H
authors.initials: H
authors.lastname: Hodes
authors.affiliation: The Center for Women's Health, Overland Park, KS, USA.
authors.forename: T
authors.initials: T
authors.lastname: Nauser
authors.affiliation: Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: M G
authors.initials: MG
authors.lastname: Petroff
mesh_terms: D000328:Adult; D003035:Cobalt / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D006801:Humans; D015778:Minor Histocompatibility Antigens / Q000235:genetics / Q000378:metabolism*; D009842:Oligopeptides / Q000235:genetics / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism*
chemical_list: C110615:HA-1 antigen; D015778:Minor Histocompatibility Antigens; D009842:Oligopeptides; D003035:Cobalt; C018021:cobaltous chloride; D010100:Oxygen
keywords: HA-1; Immune tolerance; Minor histocompatibility antigen; Oxygen; Placenta; Preeclampsia; Pregnancy; Trophoblast