Apoptosis in the trophoblast - Role of apoptosis in placental morphogenesis

Villous trophoblast is the epithelial cover of the placental villous tree and comes in direct con tact with maternal blood. The turnover of villous trophoblast includes proliferation and differentiation of cytotrophoblast, syncytial fusion of cytotrophoblast with the overlying syncytiotrophoblast, differentiation ill the syncytiotrophoblast, and finally extrusion of apoptotic material into the maternal circulation. Ill recent years, it has become clear that apoptosis is a normal constituent of trophoblast turnover and the release of appototic material does not lead to an inflammatory response of the mother. During preeclampsia there seems to be an altered balance between proliferation and apoptosis of villous trophoblast leading to a dysregulation of the release from the syncytiotrophoblast. The normal apoptotic release may be reduced ill fiavor of a necrotic release. Since apoptosis is still ongoing in the syncytiotrophoblast, a necrotic release of intrasyncytial and partly apoptotic material lead its to call this type of release "aponecrotic shedding." In this situation, cell-free components such as G-actin and DNA freely floating in maternal blood may trigger damage to the maternal endothelium, thereby triggering preeclampsia. This review highlights the importance of the apoptosis cascade in permitting normal physiologic turnover of villous trophoblast. It will demonstrate the Participation of initial stages of this cascade within the cytotrophoblast and of the execution stages within the syncytiotrophoblast. Moreover, this review presents hypotheses of how dysregulation of the apoptosis cascade may be linked to endothelial dysfunction of the maternal vasculature in preeclampsia. Copyright (C) 2004 by the Society for Gynecologic Investigation.