Placental Villous Trophoblast: the Altered Balance Between Proliferation and Apoptosis Triggers Pre-eclampsia

Journal für Reproduktionsmedizin und Endokrinologie - Journal of Reproductive Medicine and Endocrinology 2006; 3 (2): 103-108

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Keywords: Apoptose,  Molekularmedizin,  Plazenta,  Präeklampsie,  Trophoblasten,  apoptosis,  molecular medicine,  placenta,  pre-eclampsia,  proliferation,  trophoblast

During the morula stage of human embryo development segregation of the first two cell lineages takes place: the trophoblast and the embryoblast. For the development of a healthy baby, the embryonic tissues and cells need to show high rates of proliferation and differentiation, as well as high rates of apoptosis. Only the concerted action of all three processes leads to a proper development of all tissues and organs and is crucial for morphogenesis in general. This is also true for the extraembryonic tissues such as the trophoblast, which gives rise to the placenta and provides the epithelial cover of the placental villous trees. This villous trophoblast comes into direct contact with maternal blood and similar to stratified epithelia displays a continuous turnover of its layers. The villous trophoblast displays proliferation and differentiation of its precursor cells, termed villous cytotrophoblast. Their final differentiation event is syncytial fusion with the overlying multinucleated layer, the syncytiotrophoblast. Here a second differentiation stage takes place, with a final apoptotic shedding event, releasing apoptotic syncytial knots into the maternal circulation. As a normal constituent of trophoblast turnover apoptosis and the release of apoptotic material does not induce an inflammatory response of the mother. The pregnancy pathology pre-eclampsia is characterised by an altered balance between proliferation and apoptosis of villous trophoblast resulting in a dysregulated release of material from the syncytiotrophoblast into maternal blood. Beside the normal apoptotic release there seems to be an increasing release by necrosis, and due to ongoing apoptosis within the syncytiotrophoblast, the necrotic release of apoptotic material leads to aponecrotic shedding. Cell-free components of the syncytiotrophoblast may now be able to damage the maternal endothelium and hence trigger pre-eclampsia.