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

Mol Hum Reprod. 2012 Nov;18(11):535-45. doi: 10.1093/molehr/gas027. Epub 2012 Jul 4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Blotting, Western
  • Cell Line, Tumor
  • Coculture Techniques
  • Corticotropin-Releasing Hormone / biosynthesis
  • Corticotropin-Releasing Hormone / genetics*
  • Corticotropin-Releasing Hormone / pharmacology
  • Decidua / metabolism*
  • Decidua / pathology
  • Fas Ligand Protein / genetics
  • Fas Ligand Protein / metabolism
  • Female
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Macrophages / metabolism*
  • Macrophages / pathology
  • Placentation
  • Pre-Eclampsia / genetics*
  • Pre-Eclampsia / metabolism
  • Pre-Eclampsia / pathology
  • Pregnancy
  • Trophoblasts / metabolism*
  • Trophoblasts / pathology


  • FASLG protein, human
  • Fas Ligand Protein
  • Corticotropin-Releasing Hormone