Morphological and immunohistochemical assessment of intrahepatic bile duct development in the rat.

The hypotheses that intrahepatic bile ducts are derived either by a transformation of periportal liver cells or by dichotomous branching of the extrahepatic bile ducts were investigated in fetal and postnatal rat livers by histological and immunohistochemical methods using an antiserum to prekeratin which, in the liver, binds to biliary epithelial cells (BEC). In conventionally stained sections, bile duct development was observed to begin in the 19 day fetus around the larger branches of the portal vein, with the formation of lumina surrounded by cuboidal or elongated hepatoblast-like cells on the portal aspect and readily distinguished hepatoblasts on the lobular aspect. At 21 days, these structures had developed into canals of Hering lined jointly by recognizable liver cells and BEC. The number of canals of Hering per portal tract peaked at 22 days' gestation and diminished in number at birth and over the ensuing 56 h, with a concomitant increase in fully formed ducts. Bile ducts lined completely by BEC were first found at 20 days. Immunohistochemically, prekeratin antigens were first detected at 20 days in duct-like structures not only in phenotypic BEC but also in adjacent cells with an hepatoblast phenotype. Such intermediate cells were present until birth. These findings support the view that intrahepatic bile ducts develop by a reorganization and modulation of the periportal hepatoblasts to BEC.