title: Effects of increased fetuin-A in human trophoblast cells and associated pregnancy outcomes.
abstract: OBJECTIVE
  The purpose of this study was to determine whether fetuin-A affects trophoblast viability and invasion, whether growth factors that bind receptors that activate tyrosine kinase are impaired by fetuin-A, and whether elevated maternal serum fetuin-A levels are associated with adverse pregnancy outcomes.
  
  
  METHODS
  We studied viability and invasion in first-trimester extravillous trophoblast cells that were exposed to fetuin-A, insulin-like growth factor, and placental growth factor. Insulin receptor substrates expression was assessed. We compared serum fetuin-A levels in 111 preeclampsia cases and 95 controls.
  
  
  RESULTS
  Fetuin-A reduced extravillous trophoblast cell viability and invasion in the presence or absence of growth factors. Fetuin-A reduced insulin receptor substrate-1 and tyrosine phosphorylated insulin receptor substrate-1 expression in extravillous trophoblast cells that had been treated with insulin-like growth factor. Elevated serum fetuin-A levels were more prevalent in preeclampsia cases than control subjects, even after we controlled for diabetes mellitus, hypertension, and obesity.
  
  
  CONCLUSIONS
  Fetuin-A may decrease trophoblast viability and invasion caused by the inhibition of receptor tyrosine kinase activity. Elevated serum levels of fetuin-A may be associated with preeclampsia.
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Tennessee Health Sciences Center, Memphis, TN, USA.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Gomez
authors.forename: Lauren
authors.initials: L
authors.lastname: Anton
authors.forename: Sindhu K
authors.initials: SK
authors.lastname: Srinivas
authors.forename: Michal A
authors.initials: MA
authors.lastname: Elovitz
authors.forename: Samuel
authors.initials: S
authors.lastname: Parry
mesh_terms: D000328:Adult; D015153:Blotting, Western; D016022:Case-Control Studies; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000097:blood; D011247:Pregnancy; D011256:Pregnancy Outcome; D011257:Pregnancy Proteins / Q000494:pharmacology; D011261:Pregnancy Trimester, First; D011446:Prospective Studies; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism; D014327:Trophoblasts / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D055815:Young Adult; D060749:alpha-2-HS-Glycoprotein / Q000378:metabolism / Q000494:pharmacology*
chemical_list: C000608036:PGF protein, human; D011257:Pregnancy Proteins; D060749:alpha-2-HS-Glycoprotein; D000072483:Placenta Growth Factor; D007334:Insulin-Like Growth Factor I; D020794:Receptor Protein-Tyrosine Kinases