GENOME MULTIPLICATION OF EXTRAVILLOUS TROPHOBLAST CELLS IN HUMAN PLACENTA IN THE COURSE
OF DIFFERENTIATION AND INVASION INTO ENDOMETRIUM AND MYOMETRIUM. II. MECHANISMS OF POLYPLOIDIZATION
T. G. Zybina,1* H.-G. Frank,1 S. Biesterfeld,2
P. Kaufmann1
1 Department of Anatomy II, and 2 Department of Pathology, University of
Technology, Aachen, Germany;
* e-mail: zybina@mail.cytspb.rssi.ru; present address:
Institute of Cytology RAS, St. Petersburg, Russia
Peculiarities of the structure of interphase nuclei, mitotic activity, and Ki-67 protein intranuclear immune-localization were
studied to elucidate mechanisms of genome multiplication in proliferative and differentiating invasive extravillous trophoblast cells in the
human placenta. The presence of numerous chromocenters was shown to be a characteristic feature of proliferative cell nuclei of both villous
and extravillous trophoblast. At the beginning of extravillous trophoblast cell differentiation, i. e. in the proximal part of cell columns, some
amount of cells with large nuclei containing enlarged chromocenters were found. DNA content was measured simultaneously with counting
the number of chromocenters in similarly looking nuclei of squash preparations of placental villi. The increase in the ploidy level up to 4c-8c,
accompanied by a slight increase in the number of chromocenters being not proportional to the ploidy level and not exceeding the diploid
number of chromosomes of the human genome, was demonstrated. This suggests that genome multiplication of extravillous trophoblast
cells may be accomplished by endoreduplication. In addition, pictures of endomitosis were seen at early steps of differentiation of EVT cells.
The lack of polyploid mitotic figures or any obvious polyploidizing or restitutional mitoses suggests that these are not of considerable
importance in genome multiplication of human EVT cells. However, the prevalence of metaphases at the boundary of the distal part of cell
columns suggests that restitutional mitoses may be involved, even partly, in human trophoblast cell polyploidization. At later steps of
differentiation, i. e. in the distal part of cell columns, the nuclear structure obviously changes, with a uniform "network" chromatin arrangement
prevailing, whereas numerous chromocenters and features of endomitosis are no longer seen. The pattern of Ki-67 protein
immunolocalization is also changing along the invasive pathway. In the proliferating stem cells and trophoblast cells of the proximal part
of cell columns, Ki-67 was localized in the karyoplasm, chromocenters and numerous small nucleoli, whereas in the distal part of cell
columns this protein was detected predominantly in 1-2 large nucleoli. The comparative analysis of the literature data on Ki-67 localization
at different stages of cell cycle provided another evidence that EVT cells in the course of invasion may switch to the endoreduplication cycle.
In agreement with the relevant report on rodent placentation, our present data suggest that acquirement of an invasive phenotype of EVT
cells is accompanied by switching from mitotic division to endoreduplication cycle.
Key words: genome, cell nucleus, proliferation, polyploidy, endoreduplication, endomitosis, Ki-67 protein, trophoblast,
human, placenta
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