Binucleate trophoblast giant cells (BNC) are the characteristic feature of the ruminant placenta. During their development, BNC pass through 2 acytokinetic mitoses and become binucleate with 2 tetraploid nuclei. In this study, we investigate the number and location of centrosomes in bovine BNC. Centrosomes typically consist of 2 centrioles surrounded by electron-dense pericentriolar material. Duplication of centrosomes is tightly linked to the cell cycle, which ensures that the number of centrosomes remains constant in proliferating diploid cells. Alterations of the cell cycle, which affect the number of chromosome sets, also affect the number of centrosomes. In this study, we use placentomal tissue from pregnant cows (gestational days 80-230) for immunohistochemical staining of γ-tubulin (n = 3) and transmission electron microscopy (n = 3). We show that mature BNC have 4 centrosomes with 8 centrioles, clustered in the angle between the 2 cell nuclei. During the second acytokinetic mitosis, the centrosomes must be clustered to form the poles of a bipolar spindle. In rare cases, centrosome clustering fails and tripolar mitosis leads to the formation of trinucleate “BNC”. Generally, centrosome clustering occurs in polyploid tumor cells, which have an increased number of centrioles, but it is absent in proliferating diploid cells. Thus, inhibition of centrosome clustering in tumor cells is a novel promising strategy for cancer treatment. BNC are a cell population in which centrosome clustering occurs as part of the normal life history. Thus, they might be a good model for the study of the molecular mechanisms of centrosome clustering.

1.
Bettencourt-Dias, M., F. Hildebrandt, D. Pellman, G. Woods, S.A. Godinho (2011) Centrosomes and cilia in human disease. Trends Genet 27: 307-315.
2.
Björkmann, N. (1970) An Atlas of Placental Fine Structure. London, Bailliere, Tindall & Cassell.
3.
Conduit, P.T., A. Wainman, J.W. Raff (2015) Centrosome function and assembly in animal cells. Nat Rev Mol Cell Biol 16: 611-624.
4.
Firat-Karalar, E.N., T. Stearns (2014) The centriole duplication cycle. Philos Trans R Soc Lond B Biol Sci 369: 20130460.
5.
Godinho, S.A., D. Pellman (2014) Causes and consequences of centrosome abnormalities in cancer. Philos Trans R Soc Lond B Biol Scie 369: 20130467.
6.
Guidotti, J.E., O. Bregerie, A. Robert, P. Debey, C. Brechot, C. Desdouets (2003) Liver cell polyploidization: a pivotal role for binuclear hepatocytes. J Biol Chem 278: 19095-19101.
7.
Hoffman, L.H., F.B. Wooding (1993) Giant and binucleate trophoblast cells of mammals. J Exp Zool 266: 559-577.
8.
Kalatova, B., R. Jesenska, D. Hlinka, M. Dudas (2015) Tripolar mitosis in human cells and embryos: occurrence, pathophysiology and medical implications. Acta Histochem 117: 111-125.
9.
Klisch, K., E. Bevilacqua, L.V. Olivera (2005) Mitotic polyploidization in trophoblast giant cells of the alpaca. Cells Tissues Organs 181: 103-108.
10.
Klisch, K., W. Hecht, C. Pfarrer, G. Schuler, B. Hoffmann, R. Leiser (1999a) DNA content and ploidy level of bovine placentomal trophoblast giant cells. Placenta 20: 451-458.
11.
Klisch, K., C. Pfarrer, G. Schuler, B. Hoffmann, R. Leiser (1999b) Tripolar acytokinetic mitosis and formation of feto-maternal syncytia in the bovine placentome: different modes of the generation of multinuclear cells. Anat Embryol (Berlin) 200: 229-237.
12.
Klisch, K., P.D. Thomsen, V. Dantzer, R. Leiser (2004) Genome multiplication is a generalised phenomenon in placentomal and interplacentomal trophoblast giant cells in cattle. Reprod Fertil Dev 16: 301-306.
13.
Kollman, J.M., A. Merdes, L. Mourey, D.A. Agard (2011) Microtubule nucleation by gamma-tubulin complexes. Nat Rev Mol Cell Biol 12: 709-721.
14.
Mc Gee, M.M. (2015) Targeting the mitotic catastrophe signaling pathway in cancer. Mediators Inflamm 2015: 146282.
15.
Ogden, A., P.C. Rida, R. Aneja (2012) Let's huddle to prevent a muddle: centrosome declustering as an attractive anticancer strategy. Cell Death Differ 19: 1255-1267.
16.
Ogden, A., P.C. Rida, R. Aneja (2013) Heading off with the herd: how cancer cells might maneuver supernumerary centrosomes for directional migration. Cancer Metastasis Rev 32: 269-287.
17.
Watanabe, S., G. Shioi, Y. Furuta, G. Goshima (2016) Intra-spindle microtubule assembly regulates clustering of microtubule-organizing centers during early mouse development. Cell Rep 15: 54-60.
18.
Wooding, F.B. (1983) Frequency and localization of binucleate cells in the placentomes of ruminants. Placenta 4: 527-539.
19.
Wooding, F.B. (1992) Current topic: the synepitheliochorial placenta of ruminants: binucleate cell fusions and hormone production. Placenta 13: 101-113.
20.
Wooding, F.B., G. Morgan, M.R. Brandon, S. Camous (1994) Membrane dynamics during migration of placental cells through trophectodermal tight junctions in sheep and goats. Cell Tissue Res 276: 387-397.
21.
Zybina, T.G., E.V. Zybina (2005) Cell reproduction and genome multiplication in the proliferative and invasive trophoblast cell populations of mammalian placenta. Cell Biol Int 29: 1071-1083.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.