Abstract
Heparin can significantly reduce pregnancy complications in women with certain thrombophilias, such as antiphospholipid syndrome. Recent reports suggest that heparin may act by mechanisms other than anticoagulation. However, the effect of heparin on trophoblast biology in the absence of thrombophilia has not been extensively investigated. Therefore, this study aimed to evaluate trophoblast invasion, using an established cell line and primary extravillous trophoblasts (EVTs), following exposure to heparin and fractionated heparin. An EVT cell line (SGHPL-4) was used to study invasion in the presence of hepatocyte growth factor (HGF) and varying concentrations of fractionated and unfractionated heparin. These experiments were repeated using first trimester primary EVTs. Both forms of heparin significantly reduced HGF-induced invasion in the SGHPL-4 cell line. This suppression of invasion appeared to be dose-dependent for fractionated heparin. In primary EVT cells, fractionated heparin also demonstrated significant suppression of invasion. Heparin has the potential to reduce trophoblast invasion in cell lines and first trimester EVT cells. This article highlights the need for further evaluation of these medications in vitro and in vivo, especially when used in the absence of thrombophilic disorders.
Highlights
Regulation of trophoblast invasion is integral to a successful pregnancy
Culture of SGHPL-4 cells A human extravillous trophoblast (EVT) cell line, SGHPL-4, derived from primary first trimester extravillous trophoblasts (EVTs) cells was used throughout this study (Choy et al, 2000; Shiverick et al, 2001)
Heparin and fractionated heparin showed no significant effect on SGHPL-4 invasion in the absence of hepatocyte growth factor (HGF) stimulation
Summary
Regulation of trophoblast invasion is integral to a successful pregnancy. Inadequate trophoblast invasion is associated with conditions such as spontaneous abortion, fetal growth restriction, stillbirth and pre-eclampsia (Khong et al, 1986; Burton and Jauniaux, 2004). The relative success of heparin in improving pregnancy prognosis in women with previous aPLs-related pregnancy complications has led to the increased, unsupported use of heparin, and more recently fractionated heparin, in absence of confirmed thrombophilias (Tzafettas et al, 2002). METHODS: An EVT cell line (SGHPL-4) was used to study invasion in the presence of hepatocyte growth factor (HGF) and varying concentrations of fractionated and unfractionated heparin. These experiments were repeated using first trimester primary EVTs. RESULTS: Both forms of heparin significantly reduced HGF-induced invasion in the SGHPL-4 cell line. RESULTS: Both forms of heparin significantly reduced HGF-induced invasion in the SGHPL-4 cell line This suppression of invasion appeared to be dose-dependent for fractionated heparin. This article highlights the need for further evaluation of these medications in vitro and in vivo, especially when used in the absence of thrombophilic disorders
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