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PubMedDate not supplied

Disparate regulation of human fetal erythropoiesis by the microenvironments of the liver and bone marrow.

The liver and the bone marrow (BM) are the major organs that support hematopoiesis in the human fetus. Although both tissues contain the spectrum of hematopoietic cells, erythropoiesis dominates the liver. Previous studies suggested that a unique responsiveness of fetal burst-forming units erythroid (BFU-E) to erythropoietin (EPO) obviates the need for cytokines with burst-promoting activity (BPA) in fetal erythropoiesis. This potential regulatory mechanism whereby fetal erythropoiesis is enhanced was further investigated. Fluorescence-activated cell sorting was used to isolate liver and BM progenitors based on their levels of CD34 and CD38 expression. The most mature population of CD34+ lineage (Lin-) cells was also the most prevalent of the three subpopulations and contained BFU-E responsive to EPO alone under serum-deprived conditions. Kit ligand (KL) also strongly synergized with EPO in stimulating the growth of these BFU-E. An intermediate subset of CD34++CD38+Lin- cells contained erythroid progenitors responsive to EPO alone, but also displayed synergism between EPO and KL, granulocyte-macrophage colony-stimulating factor (GM-CSF), or interleukin (IL)-3, demonstrating that erythroid progenitors that respond to cytokines with BPA do exist in fetal tissues as in the adult BM. Candidate stem cells (CD34++CD38-Lin- cells) did not respond to EPO. Synergisms among KL, GM-CSF, and IL-3, and to a lesser extent granulocyte colony-stimulating factor (G-CSF) and FLK-2/FLT-3 ligand (FL), supported the growth of primitive multipotent progenitors that became responsive to EPO. These data define the limits of EPO activity in fetal erythropoiesis to cells that express CD38 and demonstrate the potential for various cytokine interactions to be involved in regulating fetal erythropoiesis. Furthermore, a comparison of the responses of liver and BM erythroid progenitors revealed similarity in their responses to cytokines but a difference in the frequency of BFU-E among the three subpopulations examined. A higher frequency of BFU-E among the intermediate and late progenitor subsets in the liver indicates that regulatory factors acting on stem cells and their immediate progeny are partially responsible for the high content of erythropoiesis in the liver. These data implicate a critical role for the microenvironments of the liver and BM in regulating the disparate levels of erythropoiesis in these tissues.

Antigens, CD↗
PubMed2025

Histone modifications in the regulation of erythropoiesis.

INTRODUCTION: The pathogenesis of anemia and other erythroid dysphasia are mains poorly understood, primarily due to limited knowledge about the differentiation processes and regulatory mechanisms governing erythropoiesis. Erythropoiesis is a highly complex and precise biological process, that can be categorized into three distinct stages: early erythropoiesis, terminal erythroid differentiation, and reticulocyte maturation, and this complex process is tightly controlled by multiple regulatory factors. Emerging evidence highlights the crucial role of epigenetic modifications, particularly histone modifications, in regulating erythropoiesis. Methylation and acetylation are two common modification forms that affect genome accessibility by altering the state of chromatin, thereby regulating gene expression during erythropoiesis. DISCUSSION: This review systematically examines the roles of histone methylation and acetylation, along with their respective regulatory enzymes, in regulating the development and differentiation of hematopoietic stem/progenitor cells (HSPCs) and erythroid progenitors. Furthermore, we discuss the involvement of these histone modifications in erythroid-specific developmental processes, including hemoglobin switching, chromatin condensation, and enucleation.Conclusions This review summarizes the current understanding of the role of histone modifications in erythropoiesis based on existing research, as a foundation for further research the mechanisms of epigenetic regulatory in erythropoiesis.

Erythropoiesis↗
PubMed2002

The role of iron in erythropoiesis in the absence and presence of erythropoietin therapy.

Preoperative autologous blood donation has served as a model for blood loss anaemia. Studies in these patients, along with clinical trials of i.v. iron and recombinant human erythropoietin (rHuEPO) therapy, have furthered our understanding of the relationship between erythropoietin, iron, and erythropoiesis. With supplemental oral iron, the endogenous erythropoietic response to routine autologous blood donation and to the anaemia of chronic illness has been shown to be modest, but predictable. In more aggressive donation and more severe anaemia, the endogenous erythropoietic response is more substantial, but still predictable. Studies in patients undergoing aggressive phlebotomy whilst receiving rHuEPO demonstrate a wide variation in response to rHuEPO dose. This variability is not related to age or gender and suggests factors such as iron-restricted erythropoiesis may be responsible. Supporting evidence arises from the superior erythropoietic response observed in patients with haemochromatosis. These patients maintain very high serum iron and transferrin saturation levels. In response to serial phlebotomy these patients can mount an endogenous erythropoietin response up to five-times greater than healthy individuals. When treated with rHuEPO, patients with haemochromatosis respond with much greater RBC expansion volumes than patients receiving rHuEPO and iron supplementation. Studies show no difference in the degree of endogenously stimulated erythropoiesis between patients with measurable iron stores and those without. However, when treated with rHuEPO, increased erythropoiesis has been observed in patients with measurable iron stores compared with those without. This suggests that, while oral iron supplementation may be sufficient to keep pace with endogenously stimulated erythropoiesis, it may not be adequate to prevent iron-restricted erythropoiesis during rHuEPO therapy. Some studies have suggested that i.v iron may prevent iron-restricted erythropoiesis during rHuEPO therapy although further research is needed. The availability of better tolerated i.v. iron preparations provides an ideal opportunity to study the value of iron therapy in patients with acute blood loss, particularly those undergoing rHuEPO therapy.

Anemia↗
PubMed1986

[Clinico-hematological studies on the activity of serum erythropoietin and erythropoiesis in hypoplastic anemia].

I have examined Ferrokinetics and the activity of serum erythropoietin (by Frieds method) for determining the in vivo erythropoiesis, additionally the presence of "effective" or "ineffective" erythropoiesis in patients with hypoplastic anemia. The number of reticulocytes and the reticulocyte production index also were analysed concerning erythropoiesis. Based on above-mentioned findings, the prognosis of these patients was analysed. Furthermore, from the relationship between the morphological examination of the erythroid cells in the bone marrow and the time course of the activity of serum erythropoietin, the change of erythropoiesis was investigated. From these results, a higher level of serum erythropoietin was observed in patients with more severe type in erythropoiesis, whereas the prognosis in these patients was much poorer in relation to an elevated value of serum erythropoietin. Furthermore, it might be suggested that a high level of erythropoietin which is enough to help the erythroid progenitor cells to differentiate and maturate to normal erythroblasts was able to shorter the maturation time of the erythroid cells and also effectively abolished "ineffective erythropoiesis" inducing the proper erythropoiesis.

Adolescent↗
PubMed1993

[Erythropoiesis and its regulation].

Erythropoiesis is the process leading to the formation of red cells. Our understanding of erythropoiesis regulation has been due to the characterization of the erythroblast progenitor cells BFU-E and CFU-E. These cells cannot be recognized morphologically, but they proliferate and differentiate in vitro under the effect of growth factors. They correspond to different steps in erythroblast differentiation which is in fact subjected to different regulations. BFU-E cells are the earliest cells of erythropoiesis and are regulated by such growth factors as GM-CSF, Il-3 or Il-9, which are not specific to erythropoiesis. As they differentiate, the BFU-E cells become sensitive to erythropoietin, the erythropoiesis-specific hormone secreted mainly by the kidney in response to hypoxia. The action of erythropoietin and that of other growth factors are synergistically reinforced by a non erythropoiesis-specific growth factor called Steel factor which plays a very important physiological role since defects in its synthesis caused by genetic anomalies produce a lethal anaemia in mice. CFU-E cells, which precede proerythroblasts, are the most sensitive to the action of erythropoietin both in vitro and in vivo. A better knowledge of erythropoiesis regulation mechanisms should help us in the understanding of the physiopathology of some congenital or acquired diseases, such as erythroblastopenia or polycythaemia vera.

Animals↗
PubMed1993

Quantitative assessment of erythropoiesis and functional classification of anemia based on measurements of serum transferrin receptor and erythropoietin.

We evaluated the quantitative value of a simple model of erythropoiesis, based on the basic assumptions that the red blood cell (RBC) mass determines erythropoietin (Epo) production, which in turn stimulates erythropoietic activity. The RBC mass was quantitated by direct isotopic measurement (RCM), Epo production by serum Epo levels, and erythropoiesis by the ferrokinetic measurement of the erythron transferrin uptake (ETU), the serum transferrin receptor (TfR) level, and the reticulocyte (retic) index, and was completed by an evaluation of overall marrow erythron cellularity. We studied a total of 195 subjects, including 31 normal individuals, 38 patients with polycythemia, and 126 patients with various forms of anemia. Instead of only quantitating Epo and erythropoiesis in absolute terms, we also evaluated them in relation to the degree of anemia or polycythemia, and expressed the results as a ratio of observed values to values predicted from the regression equations between hematocrit (Hct) on the one hand, and Epo, TfR, and ETU on the other, obtained in a carefully selected subpopulation. The slope of the regression of TfR (as well as ETU) versus Hct was very similar to the slope of the regression of Epo versus Hct. Average EPO and TfR (as well as ETU) values predicted from the regression equations were quite comparable to observed values in most groups of subjects, with exceptions predictable from knowledge of the pathophysiology of these hematologic disorders. We identified four major patterns of erythropoiesis, ie, normal, hyperdestruction (with variants of hemolysis or ineffective erythropoiesis), intrinsic marrow hypoproliferation, and defective Epo production. Dissecting out groups of patients showed much greater heterogeneity than when patients were analyzed by group. This was particularly true in the case of a hypoproliferative component being combined with hyperdestruction, giving what we called a "mixed disorder of erythropoiesis." We conclude that the pathophysiology of anemia can be assessed by a simple measurement of Hct, retic index, Epo, and TfR levels, with Epo and TfR being more informative when expressed in relation to the degree of anemia. The model is particularly useful for detecting the presence of multiple mechanisms of anemia in the same patient. However, it has limitations inherent to the relative invalidity of TfR in iron deficiency, the imprecision of a retic count, and the difficulty in distinguishing hemolysis from ineffective erythropoiesis in some patients and in recognizing a component of hyperdestruction in hypoproliferative anemia.

Adolescent↗
PubMedDate not supplied

Maintenance and expansion of erythropoiesis in human long-term bone marrow cultures in presence of erythropoietin plus stem cell factor and interleukin-3 or interleukin-11.

Recently there has been great interest in the ex vivo expansion and/or purging of human bone marrow cells prior to transplantation in order to obtain a long-lasting restoration of normal hematopoiesis and freedom from relapse. Long-term human bone marrow cultures (LTHBMC) represent the best available approximation of in vivo hematopoiesis. In the traditional LTHBMC, erythropoiesis is short lived (about 2 weeks). The longevity and productivity of erythropoiesis in LTHBMC may be limited by the insufficient production of certain cytokines such as Erythropoietin (Epo), SCF, IL-3 and/or IL-11 by the stromal and hematopoietic cells ex vivo and/or suboptimal addition of these cytokines. Therefore, we have investigated the optimal presence of erythropoietin plus SCF, IL-3, and/or IL-11 as requirements for the maintenance and expansion of erythropoiesis in LTHBMC in an effort to overcome the defective erythropoiesis of the traditional LTHBMC. In LTHBMC containing Epo alone and its combinations with SCF, IL-3, and/or IL-11, the nonadherent cells consisted mainly of erythroblast and normoblast cells which became the majority in the third and fourth weeks whereas granulocytes and macrophages declined steadily from the second week. A significant increase in the number of erythroblast and normoblast cells was produced throughout the whole period of LTHBMC containing Epo + IL-11 or Epo + SCF + IL-11 or Epo + SCF + IL-3 + IL-11. In the presence of Epo alone, BFU-E decreased steadily throughout LTHBMC. However, the erythroid clonogenic cells were successfully maintained in cultures containing Epo + SCF IL-3 or Epo + SCF + IL-11 or Epo + SCF + IL-3 + IL-11 for the 4 weeks and even significantly expanded by 4.5-5.7, 8.1-10 and 5-7-fold more than in the presence of Epo alone in the second, third and fourth weeks, respectively, p < 0.01. Our optimum cultures, including Epo + SCF + IL-3 or Epo + SCF + IL-11, maintained the production of nonadherent erythroid clonogenic cells for 4 weeks in culture, representing a significant improvement over the traditional LTHBMC that exhibits a progressive decline in erythropoiesis during the first 2 weeks. We conclude that Epo alone could not maintain erythroid clonogenic cell production and the supplementation with either of the two combinations: Epo + SCF + IL-3 or Epo + SCF + IL-11 is sufficient for maintaining erythropoiesis in LTHBMC. The present LTHBMC system should have applications to the analysis and manipulation of human erythropoiesis.

Bone Marrow↗
PubMed1983

Erythropoiesis in the developing rainbow trout, Salmo gairdneri irideus: histochemical and immunochemical detection of erythropoietic organs.

In the rainbow trout, Salmo gairdneri irideus, round, disc-like erythrocytes in the embryonic circulation (Ery L) are replaced by small, elliptical, disc-like erythrocytes (Ery ImA) after hatching. In the peripheral blood of alevins, Ery ImAs grow into mature, adult erythrocytes (Ery A) of large elliptical, disc-like shape (Iuchi, '73b; Yamamoto and Iuchi, '75). Ery L and Ery A have larval and adult hemoglobins, respectively (Iuchi, '73a). The ontogenetic sequence of hemoglobin switching and erythrocyte replacement during erythropoiesis was examined by o-dianisidine histochemistry as well as immunohistochemistry using FITC-antibody probe specific to adult hemoglobins. The first phase of embryonic erythropoiesis (for Ery L) occurs in the intraembryonic "intermediate cell mass" as well as the extraembryonic blood islands on the yolk sac. This phase of erythropoiesis is transient, continuing during the 7th to 12th day after fertilization and ceasing by the 15th day (5th day before hatching). There is a mixed population of Ery L, ImA, and A in the peripheral blood of posthatching alevins. Ery ImA and A showed immunofluorescence with FITC anti-Hb A antibody but Ery L did not. Erythroid cells, stainable with FITC anti-Hb A antibody, were observed in the kidney and the spleen 1 day before hatching and thereafter, but not in the liver throughout all stages examined. Therefore, we conclude that new erythropoiesis (erythropoiesis for Ery ImA and Ery A) began in the kidney and the spleen 1 day before hatching. These findings indicate that hemoglobin switching during the ontogeny of rainbow trout is based on erythrocyte replacement, correlated with a shift in the site of erythropoiesis from one organ to another.

Age Factors↗
PubMed1970

Stimulation of mammalian erythropoiesis by 5beta-H steroid metabolites.

The effects of a number of steroid compounds on erythropoiesis in normal and polycythemic mice were examined. Of the steroids that stimulated erythropoiesis, the hormone testosterone and certain 5beta-H C(19) and C(21) nonhormonal metabolites were the most effective. Anti-erythropoietin abolished the erythropoiesis-stimulating effects of testosterone but not those exerted by the 5beta-H steroid, 11-ketopregnanolone. Similarly, testosterone but not 11-ketopregnanolone evoked the production of erythropoiesis-stimulating factor in rats. It is concluded that two mechanisms underlie the stimulating actions of steroids on erythropoiesis; one through the production of erythropoietin and the second involving a more direct influence on the blood-forming tissues. The 5beta-H steroid metabolites are postulated to act on erythropoiesis via the latter mechanism.

Animals↗
PubMed1988

Insulin-like growth factor I stimulates erythropoiesis in hypophysectomized rats.

Stimulation of erythropoiesis during growth is necessary to ensure proportionality between erythrocyte mass and body mass. However, the way by which erythrocyte formation is adapted to body growth is still unknown. Growth arrest in hypophysectomized rats is accompanied by decreased erythropoiesis. We have, therefore, examined whether insulin-like growth factor I (IGF-I), the mediator of growth hormone effects on body growth, is able to restore erythropoiesis in these animals. Subcutaneous infusions of 120 micrograms of recombinant human IGF-I per day in hypophysectomized rats led to increases in body weight, 59Fe incorporation into erythrocytes, and the number of reticulocytes that were similar to increases caused by infusions of 28 milliunits of human growth hormone per day. Body weight gain and 59Fe incorporation were linearly correlated. Like growth hormone, IGF-I also caused a significant rise in serum erythropoietin concentrations. However, the stimulatory effect on erythropoiesis occurred before serum erythropoietin levels had risen. These results demonstrate that IGF-I mediates the stimulatory effect of growth hormone on erythropoiesis in vivo and thus further support the somatomedin concept. They also show that IGF-I can stimulate erythropoiesis in an endocrine manner, and they suggest two possible routes of action: a direct one and an indirect one by means of enhanced erythropoietin production.

Animals↗
PubMed1975

Erythropoiesis inhibiting factor(s) in intact and haemolyzed red blood cells.

A previous report have shown that both intact red blood cells (RBC) and an equal number of haemolyzed cells were able to inhibit erythropoiesis on ESF-induced erythropoiesis, suggesting a cell compound to be responsible for the inhibitiory effect. Haeme and haeme compounds have been found to stimulate or inhibit both erythropoiesis and haeme synthesis. The present work presents data on the inhibitory effect of haemolyzed RBC and compounds from intact RBC on erythropoiesis. The inhibiting factor was found to be of a small molecular size and of the same range as a urinary erythorpoiesis inhibiting factor (EIF). The inhibitor did not contain haeme. Both Fe+2 and Fe+3 were tested, showing no reduction of the 59-Fe incorporation into RBC in the test animals. The inhibition could not be due to dilution of the 59-Fe with unlabelled iron from the haemolyzed cells. On the contrary, Fe+3-ions rather stimulated erythropoiesis, probably due to increased amounts of available iron. Haemolysates were prepared from RBC with different amounts of immature cells. With increasing amounts of reticulocytes, a reduction of the inhibitory effect occurred. Also foetal cells showed less inhibition than an equal amount of adult cells. After high speed centrifugation, the inhibitory effect of haemolysates was found in the supernatant, while ghost cells exerted no inhibition. No species differences were found using both exhypoxic polycythaemic mice and rats. An inhibiting factor was liberated into the incubation medium when RBC were incubated for 20 h. No haemolysis occurred during the incubation period. Mature, adult RBC therefore contain a substance which is different from haeme, with a negative feedback on erythropoiesis.

Animals↗
PubMed2006

Real-time monitoring of stress erythropoiesis in vivo using Gata1 and beta-globin LCR luciferase transgenic mice.

Erythroid progenitors have the potential to proliferate rapidly in response to environmental stimuli. This process is referred to as stress erythropoiesis, with erythropoietin (EPO) playing central roles in its promotion. In this study, we wanted to elucidate the molecular mechanisms governing the regulation of stress erythropoiesis and the maintenance of red-cell homeostasis. This was achieved by our development of a noninvasive real-time monitoring system for erythropoiesis using transgenic mouse lines expressing luciferase under the control of the mouse Gata1 hematopoietic regulatory domain (G1-HRD-luc) or human beta-globin locus control region (Hbb-LCR-luc). Optical bioluminescence images revealed that the luciferase was specifically expressed in spleen and bone marrow and was induced rapidly in response to anemia and hypoxia stimuli. The G1-HRD-luc activity tracked the emergence and disappearance of proerythroblast-stage progenitors, whereas the Hbb-LCR-luc activity tracked erythroblasts and later stage erythroid cells. Increased plasma EPO concentration preceded an increase in G1-HRD-luc, supporting our contention that EPO acts as the key upstream signal in stress erythropoiesis. Hence, we conclude that G1-HRD-luc and Hbb-LCR-luc reporters are differentially activated during stress erythropoiesis and that the transgenic mouse lines used serve as an important means for understanding the homeostatic regulation of erythropoiesis.

Animals↗
PubMed1992

Insulin-like growth factor I and erythropoiesis.

The bone marrow, the primary site of hematopoiesis, is a self-renewing system consisting of a unique micro-environment that promotes the differentiation and proliferation of the various hematopoietic cell lines. While many critical factors necessary for red cell production have been identified, the regulation of erythropoiesis has not been completely elucidated. In addition to multi-lineage growth factors (e.g. interleukin 3 or 4) and lineage-specific hematopoietic growth factors (e.g. erythropoietin), several lines of evidence suggest a key role for insulin-like growth factor I (IGF-I). First, growth hormone stimulates erythropoiesis and IGF-I is known to mediate many of growth hormone's actions (somatomedin hypothesis). Second, factors in bovine serum and in serum from an anephric human with erythropoietic activity distinct from erythropoietin have been identified as IGFs. Third, IGF receptors are found on both erythrocyte precursors as well as mature erythrocytes. Fourth, in vitro IGF-I stimulates erythropoiesis in bone marrow cultures. Fifth, IGF-I administration to neonatal or hypophysectomized animals results in increased erythropoiesis in vivo. Recent studies indicate that IGF-I at physiologic concentrations stimulates erythropoiesis and that growth hormone's action is indirect, occurring via IGF-I. The physiologic source of IGF-I for the bone marrow may be delivery from the serum (an endocrine mechanism) or synthesis within the bone marrow by stromal or other cells (a paracrine mechanism). Our recent studies have shown that mouse bone marrow stromal cells secrete both IGF-I and IGF binding proteins (IGFBPs). The role of IGFBPs in erythropoiesis is not known, but they might modulate the local concentration of IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Immunosuppression associated with erythropoiesis in genetic low responder mice.

Priming-memory generation in response to Escherichia coli beta-D-galactosidase occurs without antibody formation in irradiated spleen-cell-transferred C57BL/6J mice, which are genetic low responders to the enzyme. Erythropoiesis abolishes priming-memory generation, so that recipients immunized a few days after cell transfer and erythropoiesis induction do not mount a secondary antibody response. Priming-memory generation in cell recipients immunized 3 days after erythropoiesis induction was less frequent than in controls, whereas no significant differences were found when antigen was given before erythropoiesis induction or 5 days after it. The mean titre of the mice escapint suppression was similar to that of the control mice, which became primed and mounted memory. The titre distribution in both responder groups were also similar, although no high-titered responders were found in the erythropoietic mice. Thus while erythropoiesis induction affects the frequency of priming-memory generation, it does not affect to the same extent the amount of memory generated in those mice escaping suppression. The same distinction was observed when spleen cells from erythropoietic mice, containing 30 to 40% erythroblasts, were transferred into normal mice. However, induction of erythropoiesis in non-irradiated non-cell=transferred mice did not cause suppression.

Animals↗
PubMed1994

Evidence suggesting a negative regulatory role for macrophages in murine erythropoiesis in vivo.

Increasing the rate of erythropoiesis in C57BL/6 mice, either by hypoxia or by the injection of recombinant erythropoietin (Epo), resulted in significant reductions in marrow macrophage number, as assessed by flow cytometry employing the monoclonal antibody against the macrophage antigen Mac-1 and by histologic determination of reductions in the number of marrow esterase-positive cells. This decline was paralleled by decreases in marrow colony-forming unit-macrophage (CFU-M) and colony-forming unit-granulocyte/macrophage (CFU-GM) number. The intramedullary concentration of the cytokines interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF-alpha), which are produced by macrophages, was also reduced. Cessation of erythropoiesis was associated with increases in macrophage number, CFU-M and CFU-GM colony number, and IL-1 alpha concentrations. Increased erythropoiesis resulted in reductions in number of burst-forming unit-erythroid (BFU-E) colonies, which were less sensitive to suppression by macrophages as evidence by less increase in colony number when macrophages were removed from the marrow before in vitro BFU-E culture. BFU-E colony number was suppressed less when IL-1 alpha and TNF-alpha were added to cultures obtained from animals with stimulated erythropoiesis. Compared to controls, BFU-E number and suppression by macrophages increased significantly when erythropoiesis was reduced. These observations provide compelling evidence for a regulatory role for macrophages in normal erythropoiesis in vivo, presumably acting as a negative balance to the stimulatory effects of Epo.

Animals↗
PubMed1997

Erythropoietin requirement for the maintenance of normal levels of erythropoiesis in the normal adult mouse.

Erythropoietin (EPO) is a glycoprotein which appears as the primary regulator of erythropoiesis under either normal or most of the pathologic conditions. In the rat with experimentally-reduced erythropoiesis, daily administration of 1.3 IRP units can restore the function and maintain steady-state conditions of red cell formation. This important information for the programming of both physiologic and pharmacologic studies is lacking for the mouse, in spite of the fact that most of the experiments performed on the regulation of erythropoiesis have been conducted in this species. In the present study, designed to determine EPO requirement for maintenance of steady-state erythropoiesis in the adult mouse under standard laboratory conditions, adult females of the CF#1 strain were exposed to hypobaria (18 h/day) during a 3-week period for induction of polycythemia (P). At the end of the hypoxic period. P mice were maintained at sea level conditions, as were normocythemic (N) mice during the entire experimental period. P mice were daily injected with 0, 0.5, 1.0, 1.5, or 2.0 IRP units of rHu-EPO during the 4-day period that followed the hypoxic one. The rate of erythropoiesis in N and P mice were measured by RBC-59Fe uptake. The plasma 59Fe half-clearance time was also measured in other groups of N and P mice similarly treated. One-way ANOVA showed that the only non-significant difference (P > 0.05) between N and EPO-injected P mice was established for the 1.0 unit dose group. It is thus suggested that approximately 1.0 unit of EPO should be synthesized daily in an adult mice to maintain a normal rate of erythropoiesis.

Animals↗
PubMed2001

Does iron-deficient erythropoiesis in pregnancy influence fetal iron supply?

BACKGROUND: It was investigated whether the iron status in newborns is negatively influenced by iron-deficient erythropoiesis of the mother during pregnancy. METHODS: The iron status is characterized by hemoglobin, erythrocyte zinc protoporphyrin and serum ferritin values. Iron-deficient erythropoiesis of the mother is characterized by erythrocyte zinc protoporphyrin values. Measurement of erythrocyte zinc protoporphyrin was performed in 103 non-anemic females within 24 hours after delivery. The iron status of their newborns was measured in cord blood. RESULTS: Erythrocyte zinc protoporphyrin concentrations were normal in 62% and elevated in 38% of the females, hence 39 women had iron-deficient erythropoiesis. There were no significant differences in mean values of the iron status parameters between neonates born to females with iron-deficient erythropoiesis and neonates born to females not having iron-deficient erythropoiesis. No correlation was found between maternal erythrocyte zinc protoporphyrin values and any of the neonatal parameters. CONCLUSION: It is concluded that fetal iron supply is not negatively influenced by iron-deficient erythropoiesis in the mother.

Anemia, Iron-Deficiency↗
PubMed1979

The regenerating liver: a site of erythropoiesis in the adult Long-Evans rat.

Erythropoiesis, which is primarily hepatic in the rat during fetal and early neonatal life, shifts almost entirely to the bone marrow in the neonatal-adolescent stage of development. In the adult, extramedullary erythropoiesis has been demonstrated in the liver and spleen under certain pathological conditions when bone marrow red cell production is insufficient. In the present study, erythropoietic foci have been found in young-adult rat liver regenerating 24-72 hr after subtotal hepatectomy. This erythropoiesis is both extravascular and sinusoidal, with some erythroblastic islands noted. The centrolobular hepatic area contains the highest concentration of erythroblasts. Peripheral blood reticulocytosis coincides with the appearance of these cells and this is considered as an indicator of effective erythropoiesis. Liver regenerating after partial hepatectomy produces significant quantities of erythropoietin (Ep) in response to hypoxia. Subtotal hepatectomy may confer upon the adult liver the ability to revert to a fetal-like condition both in its ability to produce Ep and to function as a hematopoietic inductive microenvironment for erythropoiesis.

Age Factors↗