Developing human biliary system in three dimensions

Abstract

Background: In the development of the human biliary system, although the extrahepatic bile ducts develop from the embryonic hepatic diverticulum, there is increasing evidence to suggest that the intrahepatic bile ducts originate within the liver from the ductal plate. The ductal plate develops as a sheath of primitive biliary epithelium in the mesenchyme along the portal vein branches. Through an orderly process of selection and deletion, the ductal plate is remodelled into the adult system of anastomosing tubular bile ducts. The ductal plate remodelling process occurs at the porta hepatis between 11 and 13 weeks of gestation and progresses towards the periphery of the liver.

Methods: In this project, for the first time, we have used computerised three-dimensional reconstruction techniques to visualise the developing human biliary system. Paraffin-embedded tissue from eight human embryos or fetuses between 5.5 and 16 weeks of gestation were serially sectioned, and their images were aligned, digitised, and used for three-dimensional reconstruction.

Results and conclusions: Three-dimensional images of the extrahepatic and the intrahepatic biliary systems were obtained, and the following conclusions were drawn. (1) The intrahepatic biliary system, both at the porta hepatis and within the liver, developed from the ductal plate through a consistent pattern of remodelling. (2) Prior to the remodelling process, the ductal plate was of similar morphology irrespective of site and gestation. (3) The extrahepatic biliary system was in direct luminal continuity with the developing intrahepatic biliary system throughout gestation and did not show the presence of a "solid stage" in any of the embryos or fetuses studied.