Coelomic cells show apoptosis via Fas/FasL system: a comparative study between healthy human pregnancies and missed miscarriages

Abstract

Background: The Fas/Fas ligand (FasL) system represents one of the main apoptotic pathways controlling placental apoptosis throughout gestation. In the current study, we have examined the Fas/FasL protein expression and the apoptotic incidents of coelomic cells, amniotic cells and trophoblastic tissue in first trimester human pregnancies and missed miscarriages (MM).

Methods: Protein expression was determined by immunofluoresence, western blotting analysis, immunohistochemistry and indirectly by RT-PCR, whereas apoptotic cell death was assessed by in situ DNA fragmentation analysis.

Results: Coelomic cells express Fas/FasL proteins, can undergo apoptosis and were the only cells in which apoptosis, Fas protein expression and FasL protein expression were accordingly increased along with gestational age (P = 0.001, P = 0.008; P = 0.012, respectively). In contrast, amniotic cells and trophoblast showed a consistency in the expression levels of Fas/FasL proteins in healthy pregnancies. MM were accompanied by increased Fas/FasL protein expression in all examined samples (P < 0.001). The increase of Fas/FasL protein expression was accompanied by proportional increase of apoptotic incidents among the coelomic cell population (P = 0.023, P = 0.009, respectively), whereas amniotic cells and trophoblast appeared to be resistant to Fas-induced apoptosis. The lowest expression of Fas/FasL proteins and the minimum occurrence of apoptotic incidents were detected in the trophoblast.

Conclusions: These data suggest that there is a different regulation and function of the Fas/FasL system in early human pregnancies. Aberration of the Fas-mediated apoptosis may represent one of the execution-step necessary for pregnancy loss in MM cases.