We document marked dynamic changes in murine erythropoiesis during the first 7 weeks of life while homeostatic steady-state erythropoiesis is established in the bone marrow after this period. 8 - 11 Our findings demonstrate the dynamic nature of erythropoietic organs and red cell parameters after birth. We focused on the inbred strain C57BL/6, as various models of red cell disorders have been backcrossed into this inbred strain. In the present study, we have undertaken a systematic and comprehensive analysis of the erythropoietic activity of the liver, spleen, and bone marrow and measured the red cell parameters of C57BL/6 mice from postnatal day 1 (P1) to week 12. Understanding these issues not only is of biological interest but also has significant implications by establishing the baseline for normal murine erythropoiesis and as such in interpreting the data obtained using numerous murine models of red cell disorders. Another related aspect pertains to the changes in red cell parameters, as erythropoietic activity migrates among different erythropoietic tissues. As such, it is not clear at what time during murine development steady-state erythropoiesis in the bone marrow is established. While morphologic analyses suggested splenic erythropoietic activity 2 days after birth, 7 it is unclear how long this activity persists. However, in marked contrast to the extensive studies on changes in erythropoiesis during fetal development, much less is understood about the precise timing and contribution of each site of erythropoiesis to the postnatal erythropoiesis. Consequently, there is a marked demand for red cell production during this rapid growth period. Similar to fetal development, as mice grow to adulthood and reach steady-state body weight between 8 to 10 weeks, a great expansion in blood volume and red cell mass occurs.
Definitive erythropoiesis also emerges in the yolk sac at E8.5 and then shifts to the fetal liver before transitioning to the spleen and bone marrow at E17.5. In the mouse, primitive erythropoiesis is first observed in the yolk sac from embryonic day 7.5 (E7.5) to E8.5. 2 - 4 These changes include the transition from primitive erythropoiesis to definitive erythropoiesis as well as the shifts in the sites of erythropoietic activity. 1 Developmental erythropoiesis has been extensively studied using mouse models, and it is well established that dramatic changes in erythropoiesis occur during fetal development. During the life span of mice and humans, specific anatomical sites, including the yolk sac, liver, spleen, and bone marrow, differently contribute to erythropoiesis. Our findings provide comprehensive insights into developmental changes of murine erythropoiesis postnatally and have significant implications for the appropriate interpretation of findings from the variety of murine models used in the study of normal and disordered erythropoiesis.Įrythropoiesis is the process by which red blood cells (RBCs) are produced. Mean cell volume and mean cell hemoglobin progressively decrease and reach steady state by week 3. While the red cell numbers, hemoglobin concentration, and hematocrit progressively increase after birth and reach steady-state levels by week 7, reticulocyte counts decrease during this time period. Measurement of the red cell parameters demonstrates that these postnatal dynamic changes are reflected by varying indices of circulating red cells. While the erythropoietic activity of the liver is lost 1 week after birth, that of the spleen is maintained for 7 weeks until the erythropoietic activity of the bone marrow is sufficient to sustain steady-state adult erythropoiesis. In addition to bone marrow, the liver and spleen of newborn mice sustain an active erythropoietic activity that is gradually lost during first few weeks of life. Using C57BL/6 mice, we systematically examined the age-dependent changes in liver, spleen, and bone marrow erythropoiesis following birth. However, the dynamic changes and respective contributions of the erythropoietic activity of these tissues from birth to adulthood are incompletely defined. In the mouse, the liver is the predominant site of erythropoiesis during fetal development, the spleen responds to stress erythropoiesis, and the bone marrow is involved in maintaining homeostatic erythropoiesis in adults. Liver, spleen, and bone marrow are 3 key erythropoietic tissues in mammals.
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