title: The role of fibrin matrices and tissue factor in early-term trophoblast proliferation and spreading.
abstract: BACKGROUND
  Fibrin deposition in placenta is a common phenomenon which can be triggered by villous injury and coagulation activation. Fibrin abnormalities (hypo/dysfibrinogenemia) and factor XIII deficiency are associated with infertility and pregnancy loss. While trophoblasts are known to grow on fibrin matrices, the role of this protein in trophoblast repair processes remains unclear. We hypothesize that fibrin may have an essential role in trophoblast remodeling.
  
  
  METHODS
  Morphology and spreading of primary early-term human trophoblasts and villi explants were investigated on various fibrin components. Cross-linking of matrices was evaluated by D-dimer assay. TF procoaguant activity, protein and mRNA levels in cells and villi were determined by chromogenic assay, ELISA, immunohistochemistry and reverse-transcription PCR (RT-PCR).
  
  
  RESULTS
  Fibrin but not fibrinogen, thrombin or fibronectin caused increased trophoblast proliferation and spreading. Trophoblasts cultured on factor XIII (FXIII) depleted fibrin caused their increased proliferation and spreading, associated with cross-linking. FXIII addition further increased this effect, while cell culturing on active FXIII without fibrin retained cellular proliferation. Decreased TF activity, antigen and RNA expression were demonstrated in fibrin-cultured trophoblasts and villi explants, compared to matrigel explants.
  
  
  CONCLUSIONS
  Results obtained demonstrate distinct mechanisms underlying fibrin cross-linking, which can affect trophoblast proliferation. The excess of fibrin deposits may be limited by the decrease in TF levels, thus enabling adequate placental perfusion. These findings demonstrate fibrin importance for placental repair and may partly explain poor pregnancy outcome associated with certain fibrinogen/fibrin abnormalities and FXIII deficiency.
authors.affiliation: Division of Allergy and Clinical Immunology, Bnai-Zion Medical Center, Haifa, Israel; Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel. Electronic address: ayelet.snir@b-zion.org.il.
authors.forename: Ayelet
authors.initials: A
authors.lastname: Snir
authors.forename: Benjamin
authors.initials: B
authors.lastname: Brenner
authors.forename: Baram
authors.initials: B
authors.lastname: Paz
authors.forename: Gonen
authors.initials: G
authors.lastname: Ohel
authors.forename: Naomi
authors.initials: N
authors.lastname: Lanir
mesh_terms: D048708:Cell Growth Processes / Q000502:physiology; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D011247:Pregnancy; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism*
chemical_list: D005337:Fibrin; D005340:Fibrinogen
keywords: Placenta; fibrin matrices; pregnancy; trophoblasts