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 wer e undertaken on human villous trophoblast from 13 weeks of gestation to ter m. The aim was to describe and quantify morphological changes during prolif eration, differentiation and apoptosis in cytotrophoblast and syncytial reg ions of non-aggregated and aggregated nuclei. Numbers of trophoblast nuclei increased continuously from 13 weeks. In term placentae, intrasyncytial di fferentiation was characterized ultrastructurally by gradual decreases in n uclear size and packing density accompanied by nucleolar regression, and in creasing heterochromatinization, envelope convolution and packing density o f nuclear pore complexes. In densely packed areas, nuclear profiles resembl ed interlocking jigsaw pieces. Occasionally, these 'pre-apoptotic' nuclei w ere associated with annulate lamellae. Rarely, nuclear changes terminated i n apoptosis with a characteristic pattern of condensed peripheral chromatin , a central island of euchromatin, no nucleoli and no discernible nuclear p ores. Apoptotic nuclei were seen singly and within dense nuclear aggregatio ns. Similar spatial patterns of nuclei and chromatin were seen in propidium iodide-stained sections at 13-41 weeks. Whilst the relative incidence of i ntensely: fluorescent nuclei remained constant, absolute numbers increased linearly during gestation and correlated positively with the volume of sync ytial knots. Nuclei labelled for DNA fragmentation occurred ver!: infrequen tly and were also found in nuclear clusters as well as singly. We suggest t hat nuclear differentiation in syncytium has: two phases: on entering syncy tium, nuclei become committed to a long programmed pre-apoptotic phase whic h leads to a short apoptotic execution phase. We propose further that clust ered nuclei (pre-apoptotic and apoptotic) in syncytial knots probably repre sent the extrusion component of normal continuous epithelial turnover. (C) 1999 W. B. Saunders Company Ltd.