Altered cell kinetics in cultured placental villous explants in pregnancies complicated by pre-eclampsia and intrauterine growth restriction

Placentae in pre-eclampsia (PE) and intrauterine growth restriction (IUGR) are characterized by morphological variations, apoptosis, and syncytial shedding, features that are linked to inappropriate oxygen and inflammatory cytokines. Cell turnover within the placenta is dynamic. In this study, these cellular events have been investigated longitudinally using a placental explant model. Intrinsic variations between normal (n = 14), PE (n = 16) and IUGR pregnancies (n = 11), and their responses to oxygen (3% and 17%) and exogenous tumour necrosis alpha (TNFalpha), were recorded. Placental explants were assessed for apoptotic morphology, immunolocalization of MIB-1 (a proliferation marker), lactate dehydrogenase (a necrosis marker), and human chorionic gonadotrophin (hCG, a marker of cytotrophoblast differentiation). Explants under TNFalpha and 17% O-2 revealed progressive degeneration of syncytiotrophoblast (ST) followed by restoration of hCG, localized to newly differentiated cytotrophoblasts. This differentiation was significantly enhanced in PE and IUGR. Responses to 3% O-2 were similar between groups: a sharp decline in hCG and failure to recover thereafter. Exaggerated cell death was recorded in PE and IUGR explants exposed to TNFalpha and 3% O-2. All significant changes in apoptosis were confined to ST and stromal compartments. Enhanced cell death was predominantly apoptotic in PE and necrotic in IUGR. 3% O-2 promoted cell proliferation in normal placentae but this response was not reciprocated in PE and IUGR. Elevated hCG in PE and IUGR explants may represent a placental predisposition to differentiation in vivo. In addition, the increased susceptibility of villous components to cell death, in the absence of stimulated proliferation, may provide a powerful mechanism for aberrant or adaptive placental cell turnover in utero. Copyright (C) 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley Sons, Ltd.