RGD Reference Report - Regulation of FasL/Fas in human trophoblasts: possible implications for chorioamnionitis. - Rat Genome Database

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Regulation of FasL/Fas in human trophoblasts: possible implications for chorioamnionitis.

Authors: Balkundi, Dhruv R  Ziegler, Judy A  Watchko, Jon F  Craven, Catherine  Trucco, Massimo 
Citation: Balkundi DR, etal., Biol Reprod. 2003 Aug;69(2):718-24. Epub 2003 Apr 16.
RGD ID: 12904022
Pubmed: (View Article at PubMed) PMID:12700199
DOI: Full-text: DOI:10.1095/biolreprod.102.013102

Chorioamnionitis is a common cause of premature birth and is associated with significant morbidity and mortality in the mother and infant. Preterm birth shares similarities with rejection of the fetal allograft, which is characterized by increased apoptosis of placental trophoblasts. We hypothesized that there is increased trophoblast apoptosis in chorioamnionitis and that this increased apoptosis is mediated by the Fas ligand (FasL)/Fas pathway. To test our hypothesis, we examined placental villous tissues from patients with chorioamnionitis and used the TUNEL assay to demonstrate enhanced trophoblast apoptosis in patients with chorioamnionitis. When the same samples were stained for Fas, there was increased trophoblast Fas expression in patients with chorioamnionitis. To define the mechanisms responsible for this increase in trophoblast apoptosis, we cultured villous explants from uncomplicated term placentas with proinflammatory cytokines and demonstrated a marked increase in trophoblast apoptosis. By blocking FasL, we reduced tumor necrosis factor alpha-induced and interferon gamma-induced apoptosis. These data suggest that chorioamnionitis is associated with increased trophoblast apoptosis and enhanced trophoblast Fas expression. As a complement to our in vivo study, we demonstrated that cytokine-induced trophoblast apoptosis is mediated in part by the FasL/Fas pathway, suggesting that cytokines promote sensitivity to Fas-mediated apoptosis. These mechanisms may be important in perpetuating inflammation in the placental microenvironment and may contribute to the pathogenesis of chorioamnionitis.


Disease Annotations    
chorioamnionitis  (IEP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Fas  (Fas cell surface death receptor)

Genes (Mus musculus)
Fas  (Fas (TNF receptor superfamily member 6))

Genes (Homo sapiens)
FAS  (Fas cell surface death receptor)

Additional Information