Cytomorphometry of Developing Rat Liver and Its Application to Enzymic Differentiation

Abstract

Quantitative stereological methods have been adapted for the measurement of the volume of liver attributable to parenchymal, hematopoietic, and Kupffer cells and for the measurement of the relative and absolute number (per unit volume) of these cell types and the mean volume of the parenchymal cell . These morphological parameters are the main ones for interpreting the biochemical differentiation of liver . Quantitative changes in these parameters, in rat liver between the 15th day of gestation and adult life, are presented . Despite the large number of hematopoietic cells, the parenchymal cells fill more than half of the liver volume between the 15th and 18th days of gestation and 0 .85 of the liver volume at term . The fraction of liver volume occupied by Kupffer cells is never more than 0 .02 ; the number of Kupffer cells per cubic centimeter increases less than twofold between fetal and adult life . The mean volume of individual parenchymal cells undergoes a threefold rise during late fetal life, declines in the neonatal period, and doubles between the 12th and 28th postnatal days . With the morphometric data obtained, it is impossible to convert enzyme concentrations (units per gram, determined in homogenates of whole liver) to enzyme amounts per unit volume of parenchymal or hematopoietic tissue or per individual cell of either type . In late fetal liver, only rises in enzyme concentration less than twofold may be attributed to the enrichment of parenchymal tissue at the expense of hematopoietic elements . The sudden upsurge, by more than twofold, of hepatic enzymes of the late fetal cluster (and also of the neonatal and late suckling cluster) reflects rises per parenchymal mass and per parenchymal cell . Thyroxine and glucagon, the administration of which to fetal rats promotes enzyme differentiation in liver, are without appreciable effect on the cytological parameters studied . Hydrocortisone accelerates the involution of hematopoietic tissue in fetal liver . Enzymes that are diminished by prenatal injection of hydrocortisone may be concentrated in hematopoietic cells .

Transcriptional regulation of liver development

“…Indeed between 13 and 20 dpc in the rat pre-hepatocytes on average undergo 8 doublings and the liver expands in volume by 84-fold (Greengard et al, 1972;Vassy et al, 1988;Grisham and Thorgeirsson, 1996). Gene-inactivation studies in mice have outlined a pathway that links the growth promoting properties of septum transversum mesenchyme to regulation of the hepatocyte cell cycle, recently reviewed by Zaret (1998).…”

Embryonic development of the liver†

“…Studies in rat embryos have shown that between E13.5 and E20.5, the volume of the liver expands 84-fold, during which time the hepatoblasts undergo 8-doublings. [85][86][87] Several mechanisms have been identified through gene knockout studies in mouse embryos that are required for growth of the liver. These include protection of the fetal liver from tumor necrosis factor ␣-mediated apoptotic cell death through the nuclear factor B signaling pathway, regulation of cell proliferation by the transcription factors Xbp1 and Foxm1b, and signaling mechanisms that are mediated through the AP-1 transcription factor cJun.…”

Functional polarity of the rat hepatocyte surface membrane. Isolation and characterization of plasma-membrane subfractions from the blood-sinusoidal, bile-Canalicular and contiguous surfaces of the hepatocyte

“…In liver, hepatocytes account for 70-95% of the cellular weight (lype et al, 1965;Greengard et al, 1972) and the contribution of reticulo-endothelial cell membranes to the subfractions now characterized is likely to be minor. The glucagon-stimulated adenylate cyclase activity was shown to be exclusively located in hepatocytes (Sweat & Hupka, 1971).…”