Postnatal Hepatic Development and Lgr5 ^+ve Cell Dynamics in Indigenous Rabbits: A Histomorphometric and Immunohistochemical Study

During the early postnatal period, the liver undergoes significant developmental changes essential for its maturation. Hence, this study investigated postnatal liver development in inbred indigenous rabbits (Oryctolagus cuniculus) using histological and morphometric analyses, focusing on the role of leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5)^+ve cells. Fifty clinically healthy rabbits were divided into five postnatal day groups (PND 1, 10, 15, 30 and 40). Liver samples were assessed for changes in capsule thickness, hepatocyte dimensions and non-hepatocyte cell density, while immunohistochemistry detected Lgr5 expression to evaluate stem/progenitor cell activity. Results showed a 2.8-fold reduction in liver capsule thickness, concurrent with hepatocyte and sinusoidal maturation. Haematopoietic activity and lipid droplets decreased with age, with fully organised liver architecture achieved by PND 30 and a mature histological appearance resembling that of adult liver tissue by PND 40. Kupffer cells peaked at PND 30, reflecting early immune functions, while megakaryocyte numbers declined, indicating reduced thrombopoiesis. Lgr5^+ve cells peaked at PND 10, acting as bipotential progenitors that supported hepatocyte and cholangiocyte development during liver maturation. These findings reveal that postnatal liver development involves structural maturation and immune remodelling by PND 40, with transient Lgr5^+ve cell activity playing a dynamic role in hepatic remodelling and biliary system development. This study advances our understanding of liver biology and highlights potential avenues for regenerative therapies targeting liver and biliary diseases.