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Hum. Reprod. Advance Access originally published online on July 4, 2007
Human Reproduction 2007 22(9):2523-2527; doi:10.1093/humrep/dem201
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© The Author 2007. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Effect of heparin and fractionated heparin on trophoblast invasion

R. Ganapathy1,2, G. St J. Whitley1, J.E. Cartwright1, P.R. Dash1 and B. Thilaganathan2,3

1 Centre for Developmental and Endocrine Signalling, Division of Basic Medical Sciences, St George's Hospital NHS Trust, University of London, London, UK 2 Fetal Medicine Unit, Division of Clinical Developmental Sciences, St George's Hospital NHS Trust, University of London, 4th Floor, Lanesborough Wing, Blackshaw Road, London SW17 0QT, UK

3 Correspondence address. Tel: +44-20-8725-0071; Fax: +44-20-8725-0079; E-mail: basky{at}pobox.com

BACKGROUND: 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.

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. This suppression of invasion appeared to be dose-dependent for fractionated heparin. In primary EVT cells, fractionated heparin also demonstrated significant suppression of invasion.

CONCLUSIONS: 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.

Key words: heparin/fractionated heparin/trophoblast invasion

Submitted on April 2, 2007; resubmitted on May 10, 2007; accepted on June 5, 2007.


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