Proliferation, differentiation and apoptosis in villous trophoblast at 13-41 weeks of gestation (including observations on annulate lamellae and nuclear pore complexes).

Ultrastructural, immunochemical, fluorescence and stereological studies were undertaken on human villous trophoblast from 13 weeks of gestation to term. The aim was to describe and quantify morphological changes during proliferation, differentiation and apoptosis in cytotrophoblast and syncytial regions of non-aggregated and aggregated nuclei. Numbers of trophoblast nuclei increased continuously from 13 weeks. In term placentae, intrasyncytial differentiation was characterized ultrastructurally by gradual decreases in nuclear size and packing density accompanied by nucleolar regression, and increasing heterochromatinization, envelope convolution and packing density of nuclear pore complexes. In densely packed areas, nuclear profiles resembled interlocking jigsaw pieces. Occasionally, these 'pre-apoptotic' nuclei were associated with annulate lamellae. Rarely, nuclear changes terminated in apoptosis with a characteristic pattern of condensed peripheral chromatin, a central island of euchromatin, no nucleoli and no discernible nuclear pores. Apoptotic nuclei were seen singly and within dense nuclear aggregations. Similar spatial patterns of nuclei and chromatin were seen in propidium iodide-stained sections at 13-41 weeks. Whilst the relative incidence of intensely fluorescent nuclei remained constant, absolute numbers increased linearly during gestation and correlated positively with the volume of syncytial knots. Nuclei labelled for DNA fragmentation occurred very infrequently and were also found in nuclear clusters as well as singly. We suggest that nuclear differentiation in syncytium has two phases: on entering syncytium, nuclei become committed to a long programmed pre-apoptotic phase which leads to a short apoptotic execution phase. We propose further that clustered nuclei (pre-apoptotic and apoptotic) in syncytial knots probably represent the extrusion component of normal continuous epithelial turnover. Copyright 1999 W.B. Saunders Company Ltd.