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Activation of Protein C in Human Trophoblasts in Culture and Downregulation of Trophoblast Endothelial Protein C Receptor by TNF-α

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Abstract

In mice, trophoblasts are equipped with a potent anticoagulant mechanism, the protein C pathway. In human placenta, no functional studies of the protein C pathway are available. Human first-trimester trophoblasts (CK++ HLA-G+/− Vim−) were isolated and kept in culture for a maximum of 48 hours. Activation of protein C on trophoblasts was at least as efficient as in endothelial cells (4.43 × 10−7 nmol/L/min/cell). Endothelial protein C receptor (EPCR) was expressed in syncytiotrophoblasts and extravillous trophoblasts. Downregulation of the messenger RNA of trophoblast EPCR occurred when trophoblasts were challenged with tumor necrosis factor α, and it could be prevented by unfractionated heparin but not by low-molecular-weight heparin at therapeutic doses. In conclusion, there is a functional protein C pathway on human first-trimester trophoblasts which can be modulated by inflammation. This finding has implications for the pathogenesis and prevention of placenta-mediated obstetric complications.

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Authors and Affiliations

  1. Servizio di Immunoematologia e Medicina Trasfusionale, Azienda Ospedaliera San Paolo, Polo Universitario, Italy

    E. M. Faioni MD, G. Fontana PhD & C. Razzari MD

  2. Dipartimento di Scienze della Salute, Università degli Studi di Milano, Via A. di Rudinì, 8, 20142, Milano, Italy

    G. Fontana PhD, C. Razzari MD, L. Avagliano MD, G. Bulfamante MD, E. Calvi MD, P. Doi PhD & A. M. Marconi MD

  3. U.O. Ostetricia e Ginecologia, Azienda Ospedaliera San Paolo, Polo Universitario, Italy

    L. Avagliano MD, E. Calvi MD & A. M. Marconi MD

  4. U.O. Anatomia Patologica, Azienda Ospedaliera San Paolo, Polo Universitario, Italy

    G. Bulfamante MD & P. Doi PhD

Authors
  1. E. M. Faioni MD
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  2. G. Fontana PhD
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  3. C. Razzari MD
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  4. L. Avagliano MD
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  5. G. Bulfamante MD
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  6. E. Calvi MD
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  7. P. Doi PhD
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  8. A. M. Marconi MD
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Correspondence to E. M. Faioni MD.

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Faioni, E.M., Fontana, G., Razzari, C. et al. Activation of Protein C in Human Trophoblasts in Culture and Downregulation of Trophoblast Endothelial Protein C Receptor by TNF-α. Reprod. Sci. 22, 1042–1048 (2015). https://doi.org/10.1177/1933719115570904

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