Changes in the expression of apoptosis-related proteins in the life cycle of human villous trophoblast.

The outer layer of the human placenta is the multinucleated syncytiotrophoblast. The syncytiotrophoblast is formed by the fusion of mononuclear cytotrophoblasts, and aged syncytiotrophoblast nuclei are extruded into the maternal blood as membrane-enclosed "syncytial nuclear aggregates" that are then eliminated from the maternal circulation. Apoptosis proteins are hypothesized to be involved in both of these processes, but the mechanism of death in the syncytiotrophoblast is unclear and death processes in this multinucleated layer are likely to differ from related processes in mononuclear cells. We have used a combination of villous explant culture and immunohistochemical staining of semi-serial sections from the explants to study the changing expression of 4 proteins that are markers of apoptotic processes in first-trimester human placentae. These studies show that Bcl-2 expression is limited to the syncytiotrophoblast and syncytial nuclear aggregates, while conversely Bax is expressed in some cytotrophoblasts. Activated caspase 3 and the M30 cytokeratin neoepitope were localized to isolated regions of the syncytiotrophoblast and some syncytial nuclear aggregates but were never present in the same area. Combining our results with those of others, we suggest a refined scheme whereby proteins of the apoptosis cascade participate in both the processes of syncytial formation and death.