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Effects of increased fetuin-A in human trophoblast cells and associated pregnancy outcomes

  • Luis M. Gomez
    Affiliations
    Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Tennessee Health Sciences Center, Memphis, TN
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  • Lauren Anton
    Affiliations
    Maternal and Child Health Research Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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  • Sindhu K. Srinivas
    Affiliations
    Maternal and Child Health Research Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA

    Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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  • Michal A. Elovitz
    Affiliations
    Maternal and Child Health Research Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA

    Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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  • Samuel Parry
    Affiliations
    Maternal and Child Health Research Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA

    Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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Published:October 22, 2012DOI:https://doi.org/10.1016/j.ajog.2012.10.872

      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.

      Study Design

      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.

      Conclusion

      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.

      Key words

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