Binucleation and polyploidization patterns in developmental and regenerative rat liver growth

Abstract

The hepatocellular binucleation rate, measured as the percentage of binuclear cells amongst newly formed bromodeoxyuridine-labelled and immunostained collagenase-isolated rat hepatocytes, decreased from 12% to 4% between days 30 and 40 after birth, rose to 20% between days 50 and 60, and then declined again to the adult rate of about 10% at day 80. During regenerative growth following a two-thirds partial hepatectomy, the rate of binucleation declined to about 3%, causing the fraction of binuclear cells to fall from 27% (before hepactectomy) to 5% (at 45 h after hepactectomy) as pre-existing binuclear cells replicated and formed mononuclear daughter cells. Essentially all (97%) hepatocytes replicated at least once, starting their DNA synthesis at around 13 h and reaching a peak at 30 h, irrespective of ploidy and nuclearity. At later time points, the diploid hepatocytes had a higher labelling index than the polyploid cells, suggesting a greater tendency to go through several cell cycles.

In vivo cell lineage analysis in cyproterone acetate-treated rat liver using genetic labeling of hepatocytes

“…Therefore, after partial hepatectomy as well as a mitogen-induced hyperplasia, most hepatocytes, including binucleated cells, divide and give rise to mononucleate hepatocytes, resulting in a decrease in the total number of binucleated hepatocytes. 15,32,36 Our results show that a significant (7.7%) proportion of the binucleated cells were labeled and hence derived from acytokinetic mitosis after treatment with CPA. Therefore, as suggested by Gerlyng et al, 32 during regenerative growth, a binucleation rate is also present in the liver after administration of CPA.…”

“…15,32,36 Our results show that a significant (7.7%) proportion of the binucleated cells were labeled and hence derived from acytokinetic mitosis after treatment with CPA. Therefore, as suggested by Gerlyng et al, 32 during regenerative growth, a binucleation rate is also present in the liver after administration of CPA. Finally, in contrast to other labeling strategies, retroviral-mediated genetic labeling allows the long-term analysis of cell fate in the liver.…”

“…31 The same decrease in binucleated hepatocytes is also observed after administration of various mitogens such as CPA, 4-acetylaminofluorene, and 2-AAF but not lead nitrate. 15,[31][32][33][34] Two mechanisms may account for the decrease in binucleated hepatocytes. The fraction of binucleated cells could be diluted by expansion of 34,35 Alternatively, it has been postulated that regenerative and hyperplastic growths, in contrast to developmental growth, are predominantly nonpolyploidizing with a decrease in the binucleation rate.…”

Oxidative stress promotes pathologic polyploidization in nonalcoholic fatty liver disease

“…In these circumstances, the liver polyploidy profile can also be modified. Signals promoting hepatocyte polyploidy include liver regeneration following partial hepatectomy (14), metabolic overload (15,16), chemical overload (17), oxidative damage (18), and viral infection (5). However, the cellular and molecular mechanisms regulating polyploidy in these different situations are not fully understood.…”

Investigation of the Biochemical and Histological Changes Induced by Zearalenone Mycotoxin on Liver in Male Mice and the Protective Role of Crude Venom Extracted from Jellyfish <i>Cassiopea Andromeda</i>

“…DNA replication, mitosis and cytokinesis usually evolve in a coordinated way, and each diploid cell yields two diploid daughters [43]. However, if DNA replication and mitosis occur without cytokinesis, the cell becomes binucleated or if DNA replication occurs without mitosis or cytokinesis, the ploidy of the nucleus doubles [44]. The increased occurrence of binucleate heaptocytes was hypothesized that they may be an index of the severity of hepatic illness and that binuclearity may be interpreted as a cell state that is more capable of responding to a major demand for protein synthesis.…”