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Mol. Hum. Reprod. Advance Access originally published online on August 17, 2007
Molecular Human Reproduction 2007 13(9):663-673; doi:10.1093/molehr/gam054
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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

Abortion is associated with increased expression of FasL in decidual leukocytes and apoptosis of extravillous trophoblasts: a role for CRH and urocortin

V. Minas1,{dagger}, U. Jeschke2,{dagger}, S.N. Kalantaridou1, D.U. Richter3, T. Reimer3, I. Mylonas2, K. Friese2 and A. Makrigiannakis1,4

1 Laboratory of Human Reproduction, Department of Obstetrics and Gynaecology, Medical School, University of Crete, Heraklion 71003, Greece 2Department of Obstetrics and Gynaecology, Ludwig Maximilians University of Munich, Maistrasse 11, 80337 Munich, Germany 3Department of Obstetrics and Gynaecology, University of Rostock, Rostock, Germany

4 Correspondence address. Tel: +302810392131; Fax: +302810392131; E-mail: makrigia{at}med.uoc.gr

Human reproduction is remarkably inefficient, with more than half of spontaneous conceptions failing to complete the first trimester. However, little is known on the molecular events that take place at the implantation site during abortion. Here, we examined the hypothesis that the expression of the proapoptotic Fas/FasL system at the implantation site is impaired in abortions. We found that, in contrast to normal pregnancy, abortive deciduas contain leukocytes that are positive for FasL and extravillous trophoblasts (EVTs), which show increased expression of Fas and increased rates of apoptosis. In addition, the neuropeptides, corticotropin-releasing hormone and urocortin, were elevated in placental material obtained from abortions. In vitro, these peptides induced the expression of FasL in decidual lymphocytes (DL) obtained from elective termination of pregnancy placentas and thus potentiated the cells' ability to induce Fas-mediated apoptosis in an EVT-based hybridoma cell line. Finally, DL from abortion sites effectively induced apoptosis of EVT without prior treatment. It is possible that these events may impede successful early placentation and thus contribute to the pathophysiology of human abortion.

Key words: abortion/CRH/extravillous trophoblast/FasL/implantation

{dagger} These two authors contributed equally.

Submitted on June 12, 2007; resubmitted on July 10, 2007; accepted on July 17, 2007.


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