Expression of BCL-2, BAX and BAK in the trophoblast layer of the term human placenta: a unique model of apoptosis within a syncytium

The regulation of apoptosis in the syncytiotrophoblast is of particular int erest because this is the only true syncytial epithelium in human cell biol ogy. Nuclei characteristic of apoptotic cells have been localized to this s yncytium especially in association with fibrin-containing fibrinoid deposit s. The factors responsible for regulating cell death-like features in the t rophoblast syncytium are unknown. We tested the hypothesis that fibrin was required for trophoblast apoptosis. TUNEL (terminal deoxynucleotidyltransfe rase-mediated dUTP end-labelling) staining to detect DNA fragmentation typi cal of apoptosis was performed in term human placentae revealing labelled n uclei associated with fibrin-type fibrinoid, as well as labelled nuclei in discrete areas of syncytiotrophoblast without fibrin. We also hypothesized that members of the BCL-2 family of apoptosis-associated proteins contribut e to the regulation of syncytiotrophoblast apoptosis. To identify members o f this protein family that might regulate trophoblast apoptosis, we assesse d expression of three important members of the bcl-2 gene family. We used i mmunohistochemistry with monoclonal antisera against human BCL-2 and polycl onal antisera against human BAX and BAK to study paraffin-embedded sections of human term placentae (n=5) from uncomplicated pregnancies. The anti-apo ptotic BCL-2 protein was expressed throughout the syncytium of normal villi with much less staining in cytotrophoblast. Staining was also seen adjacen t to fibrin deposits and in syncytium overlying fibrin deposits. Expression of the pro-apoptotic BAX protein was undetectable in the syncytiotrophobla st, was expressed in rare cytotrophoblast and was prominent in connective t issue and perivascular cells within the villous core. Localization of a sec ond pro-apoptotic protein, BAK, revealed immunoreactivity in isolated areas of intact syncytium of normal villi. Additionally, fibrin deposits were as sociated with intense BAK staining in both syncytiotrophoblast and cytotrop hoblast. From these data, we speculate that modulation of BAK expression is one factor regulating apoptosis in human trophoblast. (C) 2000 Harcourt Pu blishers Ltd.