In the fetal DA rat liver, hematopoiesis occurs around day 14 to day 20 of gestation, although the maximum number of hematopoietic cells are observed on day 18. After birth, the hematopoietic foci mostly disappear. Morphological analysis by light and electron microscopy reveals changes in hematopoiesis during gestation. Supporting techniques for histological study such as density fractionation and cell-scatter analysis are also employed for fractionation of fetal liver hematopoietic cells, but these methods are not sufficiently useful for clarifying the gestational changes in fetal liver hematopoiesis or for the enrichment of hematopoietic stem cells in fetal rat liver. Immunocytological and immunohistological methods using a monoclonal antibody against rat fetal liver hematopoietic cells (UB-12) established by us as well as other monoclonal antibodies (OX7 and W3/13) to rat hematopoietic cells are effective for analysis of rat hematopoietic tissues: The antigenic expressions detected by UB-12 are extensive when hematopoiesis in fetal liver is active, while decreases in parallel with the decrease of hematopoiesis. Using UB-12 monoclonal antibody and radioimmunoassay, it is possible to follow the shift of hematopoietic focus from fetal liver to adult bone marrow semiquantitatively. Some surface antigens of hematopoietic cells such as cell adhesion molecules are important for cell-cell interaction between hematopoietic cells and stromal cells and UB-12 antigen might be one of such molecules. The expression of antigens on hepatocytes detected with monoclonal antibodies directed against adult hepatocytes (HAM4 and others) is negative or quite low in the early gestational period and increases in later stages. However, even before birth the degree of expression is lower than the adult level. The morphological changes occurring with the transition from fetal-type to adult-type hepatocytes also become obvious towards the birth proving distinct difference between fetal hepatocytes and adult hepatocytes, and suggesting stromal function of fetal hepatocyte for the hematopoietic cells. These results suggest populational and cellular changes in both hematopoietic cells and hepatocytes during the gestation and it is possible to propose a theoretical cell-cell interaction through cell membrane molecules with adhesive function between hematopoietic cells and fetal hepatocytes. Also, paracrine type of cell-cell interaction may be important for fetal hematopoietic cells and hepatocytes to proliferate. Thus, the diminution of hematopoietic foci in the liver after day 19 of gestation can be explained partly by changes in the cell-cell interaction of hematopoietic cells with fetal hepatocytes, while the changes occurring in the whole body of the fetus in the perinatal period, such as the start of bone and bone marrow formation, and endocrinological or metabolic changes around birth may also be important. The mechanisms responsible for the shift of hematopoietic foci are discussed, focusing on the shift of hematopoietic foci from fetal liver to adult bone marrow.
