A Practical Approach, Second Edition=Ronald D. Ho.pdf

1084 DEVELOPMENTAL REPRODUCTIVE TOXICOLOGY: A PRACTICAL APPROACH, SECOND EDITIONFetal Liver HematopoiesisThe fetal liver serves as the initial hematopoietic tissue in early gestation (in some species it servesas the primary hematopoietic tissue throughout gestation) and is characterized by the emergenceand rapid expansion of lineage restricted progenitor cells for all types of leukocytes.HumansLymphocyte progenitors appear in human fetal liver at approximately the 7-8th week followingconception (Migliaccio et al., 1986). Thus, an early period of susceptibility occurs during cellmigration and early lymphohematopoiesis during which stem cells and lineage-committed progenitorsare at risk (~7-10 weeks post-conception).MiceHSC migrate to the developing fetal liver by gestation day 10 in mice (Cumano and Godin, 2001and Cumano et al., 2001). Differentiation of HSC to form lineage-restricted subpopulations of stemcells for the lymphoid and myeloid cell lineages has not been demonstrated prior to gestationalday 10 in mice (Godin et al., 1999). Interestingly, the period of rapid hematopoietic progenitor cellexpansion in fetal liver is not accompanied by wholesale differentiation to mature immunocompetentcell phenotypes (Godin et al., 1999). In fact, mature lymphocytes are not found in the developingliver until day 18 of gestation in the mouse, and after the initiation of hematopoiesis in embryonicbone marrow (Kincade, 1981).RatsNo information available.DogsNo information available.PrimatesNo information available.Development of the SpleenThe role of the spleen in the immune system varies both across the timeline of development andaccording to a distinct species-specificity. The development of other relevant immune organs (e.g.,lymph nodes, Peyer’s patches, etc.) will be discussed as appropriate. The development of the thymusis discussed below.HumansSites of lymphopoiesis begin to develop in the human fetus over the last half of the first trimester,starting with thymic stroma, which forms during the 6th week post-conception (Haynes et al.,1988). Stem cells and T-cell progenitors begin migration from fetal liver to thymus during the 9thweek, while B-cell progenitors appear in blood by about week 12 (Loke, 1978; vonGaudecker,1991; Kendall, 1991; Royo et al., 1987). Gut-associated lymphoid tissue develops from week 8onward, beginning with the lamina propria during weeks 8-10, followed by Peyer’s patches and© 2006 by Taylor & Francis Group, LLC