Elsevier

Placenta

Volume 20, Issues 5–6, July 1999, Pages 407-422
Placenta

Regular Article
Proliferation, Differentiation and Apoptosis in Villous Trophoblast at 13–41 Weeks of Gestation (Including Observations on Annulate Lamellae and Nuclear Pore Complexes)

https://doi.org/10.1053/plac.1999.0399Get rights and content

Abstract

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.

References (76)

  • TM Mayhew et al.

    Methodological problems in placental morphometry: apologia for the use of stereology based on sound sampling practice

    Placenta

    (1988)
  • TM Mayhew et al.

    Microscopical morphology of the human placenta and its effects on oxygen diffusion: a morphometric model

    Placenta

    (1986)
  • TM Mayhew et al.

    Changes in oxygen diffusive conductances of human placentae during gestation (10–41 weeks) are commensurate with the gain in fetal weight

    Placenta

    (1993)
  • DM Nelson

    Apoptotic changes occur in syncytiotrophoblast of human placental villi where fibrin type fibrinoid is deposited at discontinuities in the villous trophoblast

    Placenta

    (1996)
  • CD Ockleford et al.

    Propidium iodide as a nuclear marker in immunofluorescence. I. Use with tissue and cytoskeleton studies

    J Immunol Methods

    (1981)
  • N Sakuragi et al.

    Bcl-2 expression and apoptosis in human trophoblast

    Troph Res

    (1997)
  • RA Simpson et al.

    From 13 weeks to term, the trophoblast of human placenta grows by the continuous recruitment of new proliferative units: a study of nuclear number using the disector

    Placenta

    (1992)
  • SC Smith et al.

    Placental apoptosis in normal human pregnancy

    Am J Obstet Gynecol

    (1997)
  • KZM Ali et al.

    Does hypercapillarization influence the branching pattern of terminal villi in the human placenta at high altitude?

    Placenta

    (1996)
  • GG Altmann et al.

    Cell number as a measure of distribution and renewal of epithelial cells in the intestine of growing and adult rats

    Am J Anat

    (1967)
  • H Alvarez et al.

    Syncytial proliferation in normal and toxemic pregnancies

    Obstet Gynecol

    (1967)
  • H Arnholdt et al.

    Proliferation of villous trophoblast of the human placenta in normal and abnormal pregnancies

    Virchows Archiv B Cell Pathol

    (1991)
  • JD Bancroft et al.

    Manual of Histological Techniques

    (1984)
  • TN Blankenship et al.

    Developmental expression of Ki-67 antigen and proliferating cell nuclear antigen in macaque placentas

    Devel Dynamics

    (1994)
  • JD Boyd et al.

    The Human Placenta

    (1970)
  • GJ Burton

    Intervillous connections in the mature human placenta: instances of syncytial fusion or section artifacts?

    J Anat

    (1986)
  • S Chua et al.

    Trophoblast deportation in pre-eclamptic pregnancy

    Br J Obstet Gynaecol

    (1991)
  • VC Cordes et al.

    High content of a nuclear pore complex protein in cytoplasmic annulate lamellae of Xenopus oocytes

    Eur J Cell Biol

    (1995)
  • M-C Dabauvalle et al.

    Spontaneous assembly of pore complex-containing membranes (‘annulate lamellae’) in Xenopus egg extract in the absence of chromatin

    J Cell Biol

    (1991)
  • L Dearden et al.

    Structure of human trophoblast: correlation with function

  • EM DiFederico et al.

    Apoptosis is increased in invasive cytotrophoblasts from preeclamptic placentas in vivo, and cannot be induced by short-term hypoxia in vitro

    Am J Obstet Gynecol

    (1997)
  • H Fox

    The significance of villous syncytial knots in the human placenta

    J Obstet Gynaecol Br Commonwealth

    (1965)
  • Y Gavrieli et al.

    Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation

    J Cell Biol

    (1992)
  • HJG Gundersen et al.

    The efficiency of systematic sampling in stereology and its prediction

    J Microsc

    (1987)
  • T Hirsch et al.

    The apoptosis-necrosis paradox. Apoptogenic proteases activated after mitochondrial permeability transition determine the mode of cell death

    Oncogene

    (1997)
  • B Huppertz et al.

    Apoptosis of villous trophoblast in the human placenta

    Placenta

    (1997)
  • B Huppertz et al.

    Villous cytotrophoblast regulation of the syncytial apoptotic cascade in the human placenta

    Histochem Cell Biol

    (1998)
  • H Ikeda et al.

    Apoptosis is a major mode of cell death caused by ischaemia and ischaemia/reperfusion injury to the rat intestinal epithelium

    Gut

    (1998)
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