Factor seven activating protease (FSAP) expression in human placenta and its role in trophoblast migration

Mariana S. Parahuleva, Justus-Liebig-University, Giessen, Germany
Nelli Ball, Justus-Liebig-University, Giessen, Germany
Behnoush Behnoush Parviz, Justus-Liebig-University, Giessen, Germany
Daniel Zandt, Justus-Liebig-University, Giessen, Germany
Yaser Abdallah, Aga Khan University
Harald Tillmanns, Justus-Liebig-University, Giessen, Germany
Hans Hoelschermann, Krankenhaus Bad Homburg Innere Medizin I – Kardiologie, Bad Homburg, Germany
Sandip M. Kanse, Justus-Liebig-University, Giessen, Germany

This work was published before the author joined Aga Khan University.

Abstract

Objectives Factor seven activating protease (FSAP) is a plasma serine protease known to play a critical role in hemostasis and remodeling processes: FSAP levels increase markedly during normal pregnancy. In order to define the role of FSAP in vascular pathophysiology in pregnant women and particularly in the placenta, we performed this study (i) to evaluate the FSAP expression in human placenta and (ii) to identify the role of FSAP in human trophoblast migration.

Study design FSAP expression in placental tissues was analyzed by using immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). To determine whether FSAP plays any role in trophoblast migration, we used human trophoblast cells in transwell migration assays.

Results Immunohistochemistry showed that FSAP protein was expressed by syncytiotrophoblast and in the cytoplasma of invasive extravillous trophoblasts (EVT) within the maternal decidua (DC) in implantation sites of human first trimester placenta. Furthermore, FSAP mRNA and protein decreased with gestational age (p < 0.05, 1st vs 3rd trimester). FSAP (10 μg/ml) had a significant stimulatory effect on the migration of human trophoblast cells. This effect was abolished by addition of aprotinin to block the enzymatic activity of FSAP.

Conclusions The high expression level of FSAP in the placenta supports a relevant role of this protease in trophoblast migration and vascular remodeling, identifies a new concept of coagulation/fibrinolysis at the feto-maternal interface and may be essential for the maintenance of pregnancy.