Journal Article

Aberrant expression of corticotropin-releasing hormone in pre-eclampsia induces expression of FasL in maternal macrophages and extravillous trophoblast apoptosis

G. Petsas, U. Jeschke, D.U. Richter, V. Minas, A. Hammer, S. Kalantaridou, B. Toth, C. Tsatsanis, K. Friese and A. Makrigiannakis

in MHR: Basic science of reproductive medicine

Published on behalf of European Society of Human Reproduction and Embryology

Volume 18, issue 11, pages 535-545
Published in print November 2012 | ISSN: 1360-9947
Published online July 2012 | e-ISSN: 1460-2407 | DOI: https://dx.doi.org/10.1093/molehr/gas027
Aberrant expression of corticotropin-releasing hormone in pre-eclampsia induces expression of FasL in maternal macrophages and extravillous trophoblast apoptosis

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Corticotropin-releasing hormone (CRH) and its receptors are expressed in human placenta. Recently, the impaired function of this system has been associated with a number of complications of pregnancy, including pre-eclampsia. The aim of the study was to test the hypothesis that CRH participates in the pathophysiology of pre-eclampsia through the induction of macrophage-mediated apoptosis of extravillous trophoblasts (EVTs). We found that the expression of CRH was increased in the EVT of the placental bed biopsy specimens from pre-eclamptic pregnancies (1.8-fold increase; P < 0.05). In addition, significantly larger numbers of apoptotic EVT were detected in pre-eclamptic placentas compared with normal ones (P < 0.05), and only in pre-eclamptic placentas, decidual macrophages were found to be Fas ligand (FasL)-positive. In vitro studies on the effect of CRH on human macrophages suggested that CRH induced the expression of the FasL protein in human macrophages and potentiated their ability to induce the apoptosis of a Fas-expressing EVT-based hybridoma cell line in co-cultures. These findings demonstrate a possible mechanism by which the aberrant expression of CRH in pre-eclampsia may activate the FasL-positive decidual macrophages, impair the physiological turnover of EVT and eventually disturb placentation.

Keywords: CRH; FasL; macrophages; EVT; pre-eclampsia

Journal Article.  6122 words.  Illustrated.

Subjects: Reproductive Medicine

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