Intrahepatic bile duct development in the rat: a cytokeratin-immunohistochemical study

The development of the intrahepatic bile ducts was studied in rats from day 12 of gestation until 10 days of age using three antibodies directed against cytokeratins in an immunohistochemical procedure on paraffin-embedded liver tissue. In adult rat liver, both hepatocytes and bile ducts were stained by the monoclonal anti-cytokeratin no. 8, whereas two polyclonal antibodies stained bile ducts only. Hepatocytes in developing rat liver were stained by monoclonal anti-cytokeratin no. 8 from day 12 of gestation on. On day 16, cells strongly immunoreactive for cytokeratin no. 8 were observed in a string of pearl-like arrangement around large vascular branches close to the liver hilum. Over the following days, similar structures appeared throughout the liver. Gradually, lumina were formed in these structures, again starting at the liver hilum and resulting in the formation of individual bile ducts. Immunoreactivity with the polyclonal antibodies was first detected in some of the string of pearl-like structures on day 19 and gradually increased until the intensity observed in adult rat liver was reached on day 1 after birth. Even on day 10, portal spaces still revealed more bile duct branches, rings of cells strongly positive for cytokeratin no. 8 and weakly positive with the polyclonal antibodies were present. It is concluded that the intrahepatic bile ducts develop from hepatocytes. The cells closest to large vascular spaces first become strongly positive for cytokeratin no. 8 and only later on acquire additional ("bile duct type") cytokeratins. This process starts at the liver hilum and spreads through the liver. Even at 10 days of age the bile duct system is still immature: around the smaller portal vein branches, rings of cells are still undergoing transformation into bile duct type cells. These data might be useful for reevaluation of pathologic phenomena.