Gabor Than Award Lecture 2006: pre-eclampsia and villous trophoblast turnover: perspectives and possibilities.

Placental apoptosis is exaggerated in pre-eclampsia and cytotrophoblast proliferation is enhanced. This imbalance may be a primary pathogenic event, whereby excessive syncytiotrophoblast apoptosis counters cytotrophoblast fusion, promoting the liberation of syncytial material which perturbs the maternal vascular endothelium. We have previously shown that primary trophoblasts and explant cultured villous fragments from pre-eclamptic pregnancies elicit greater levels of terminal differentiation and apoptosis. This review considers current opinions in trophoblast cell turnover in normal pregnancy and pre-eclampsia. In the context of other findings, this review highlights: (i) the disparity in expression of pro-apoptotic transcription factor p53 in the syncytiotrophoblast in pre-eclampsia, (ii) the importance of reactive oxygen species and hypoxia in initiating villous trophoblast apoptosis and (iii) the concept that aberrant intervillous haemodynamics, as opposed to oxygen per se, initiates excessive syncytiotrophoblast shedding. Finally, therapeutic ways of restoring the syncytiotrophoblast in pre-eclampsia and preventing excessive placental apoptosis are considered, including a role for mitotic manipulators and growth factor replacement strategies.