The postnatal decline of hemoglobin F synthesis in normal full-term infants.

Bard, Harry

doi:10.1172/jci107943

Cited by 94 publications

(52 citation statements)

References 10 publications

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“…Fetal red cells during the 1 st trimester exclusively contain Hb F [11], while adult F cells contain both Hb F and Hb A, with a variable proportion of Hb F ranging up to 25% of the total Hb in adult F cells [12]. The correlation between %Hb F level and %F cells among non-pregnant adult subjects suggests that an increase in number of adult F cells by 1.0% results in an increase in %Hb F by 0.1% [13] implying that Hb F accounts for an approximately 10% of the total Hb in adult F cells.…”

Section: Discussionmentioning

confidence: 99%

Changes in hemoglobin F levels in pregnant women unaffected by clinical fetomaternal hemorrhage

Yamada¹,

Morikawa²,

Yamada³

et al. 2013

Clinica Chimica Acta

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Complete automation of high-performance liquid chromatography (HPLC) for determination of hemoglobin F (%Hb F) and hemoglobin A1c (%Hb A1c) levels has made this procedure available in many clinical laboratories. However, the physiological changes in %Hb F during pregnancy and the effects of physiological and supraphysiological levels of %Hb A1c on measurement of %Hb F have not been studied extensively. Simultaneous determination of %Hb F and %Hb A1c was conducted in 490 blood samples obtained before (n = 21), during 1 st (n = 150), 2 nd (n = 116), and 3 rd (n = 192) trimesters of pregnancy, and postpartum (n = 11) from 357 women, including 60 women with hyperglycemia but unaffected by clinical fetomaternal hemorrhage, by HPLC. Mean (SD) Hb F levels were 0.71% (0.25%) before pregnancy. The value of 0.82% (0.47%) during 1 st trimester decreased significantly to 0.66% (0.35%) during 2 nd trimester and to 0.58% (0.38%) during 3 rd trimester. The level was 0.62% (0.31%) approximately one year after delivery. Thus, %Hb F was highest during 1 st trimester of pregnancy. The effects of varied %Hb A1c levels on %Hb F measurements were clinically negligible. Our data may be used as reference intervals of %Hb F determined with HPLC during pregnancy.

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Section: Discussionmentioning

confidence: 99%

Changes in hemoglobin F levels in pregnant women unaffected by clinical fetomaternal hemorrhage

Yamada¹,

Morikawa²,

Yamada³

et al. 2013

Clinica Chimica Acta

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“…Adult hemoglobin, a232, is first detected at around the 10th week of gestation and accounts for approximately 10% of all hemoglobins present until about the 30th week of gestation, when increasing amounts of adult hemoglobin are produced (1). By the time the infant is 6 months old, most of the hemoglobin present is adult hemoglobin (2). The mechanisms for the switching of hemoglobins during fetal development are presently not clear (3).…”

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confidence: 99%

Proportion of fetal hemoglobin synthesis decreases during erythroid cell maturation.

Chui¹,

Wong²,

Enkin³

et al. 1980

Proc. Natl. Acad. Sci. U.S.A.

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Peripheral blood mononuclear cells from pregnant and postpartum women were cultured in vitro with erythropoietin. Burst-forming unit (BFU-E)derived erythroid colonies composed of immature erythroblasts with low hemoglobin contents were observed by day 8 of culture. By day 12 of culture, numerous BFU-E-derived erythroid colonies with high hemoglobin contents were present. The Y/(y + f) globin synthetic ratio was approximately 12% in the early cultures and 6% in the late cultures, indicating that the proportion of fetal hemoglobin synthesis decreases during erythroid cell maturation. These studies also reveal that the capacity for fetal hemoglobin production by peripheral blood BFU-E in vitro is not altered during pregnancy.The major hemoglobin in humans during intrauterine life is fetal hemoglobin, a2Y2. Adult hemoglobin, a232, is first detected at around the 10th week of gestation and accounts for approximately 10% of all hemoglobins present until about the 30th week of gestation, when increasing amounts of adult hemoglobin are produced (1). By the time the infant is 6 months old, most of the hemoglobin present is adult hemoglobin (2). The mechanisms for the switching of hemoglobins during fetal development are presently not clear (3). These orderly ontogenetic changes provide an excellent model for studying gene regulation and expression. In addition, elucidation of the mechanisms for hemoglobin switching can provide a potentially useful approach to the therapy of patients with genetic disorders involving the j globin chain.Immature erythroid stem cells, burst-forming units that respond to erythropoietin (BFU-E), are present in adult human peripheral blood and can proliferate and differentiate into large colonies of erythroblasts in vitro (4, 5). These erythroblasts, derived from normal adult individuals, synthesize a substantial amount of fetal hemoglobin (6-8). Because HbF is increased in maternal peripheral blood during pregnancy (9-11), the present investigation was undertaken to determine if peripheral blood BFU-E in pregnant women have an increased capacity for HbF production in culture and to study the pattern of HbF synthesis during erythroid cell maturation in vitro. Evidence is presented that the capacity for HbF production by peripheral blood BFU-E in vitro is not altered during pregnancy. These studies also reveal that the proportion of HbF synthesis decreases during erythroid cell maturation. A preliminary report of these studies has been published elsewhere (12). METHODSSubjects. Forty-four pregnant and postpartum (3-7 months) women were studied. All women were healthy and had no known diseases or complications. Appropriate consent was obtained. [50][51][52][53][54][55][56][57][58][59][60] Ci/mmol; 1 Ci = 3.7 X 1010 becquerels), obtained from New England Nuclear, was added to each plasma clot on either day 6 or day 7, and either day 11 or day 12 of culture. Twenty-four hours later, 10 plasma clots thus labeled were pooled and washed twice with phosphate-buffered saline. Three milligrams o...

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“…HbF synthesis declines from 85-90% to less than 30% and further drops to less than 2% by one year of age and less than 1% in adults. 1,2 Numerous studies have attempted to identify the cellular and molecular mechanisms controlling the perinatal Hb switch. 3 In vitro and in vivo studies on fetal liver and cord blood (CB) hematopoietic progenitor cells (HPCs) indicate that the level of HbF synthesis in erythroid cells is regulated by a developmental clock, [4][5][6] i.e.…”

Section: Introductionmentioning

confidence: 99%

Mechanism of human Hb switching: a possible role of the kit receptor/miR 221-222 complex

Gabbianelli

Testa²,

Morsilli³

et al. 2010

Haematologica

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BackgroundThe human hemoglobin switch (HbF→HbA) takes place in the peri/post-natal period. In adult life, however, the residual HbF (<1%) may be partially reactivated by chemical inducers and/or cytokines such as the kit ligand (KL). MicroRNAs (miRs) play a pivotal role in normal hematopoiesis: downmodulation of miR-221/222 stimulates human erythropoietic proliferation through upmodulation of the kit receptor. Design and MethodsWe have explored the possible role of kit/KL in perinatal Hb switching by evaluating: i) the expression levels of both kit and kit ligand on CD34 + cells and in plasma isolated from pre-, mid-and full-term cord blood samples; ii) the reactivation of HbF synthesis in KL-treated unilineage erythroid cell cultures; iii) the functional role of miR-221/222 in HbF production. ResultsIn perinatal life, kit expression showed a gradual decline directly correlated to the decrease of HbF (from 80-90% to <30%). Moreover, in full-term cord blood erythroid cultures, kit ligand induced a marked increase of HbF (up to 80%) specifically abrogated by addition of the kit inhibitor imatinib, thus reversing the Hb switch. MiR-221/222 expression exhibited rising levels during peri/post-natal development. In functional studies, overexpression of these miRs in cord blood progenitors caused a remarkable decrease in kit expression, erythroblast proliferation and HbF content, whereas their suppression induced opposite effects. ConclusionsOur studies indicate that human perinatal Hb switching is under control of the kit receptor/miR 221-222 complex. We do not exclude, however, that other mechanisms (i.e. glucocorticoids and the HbF inhibitor BCL11A) may also contribute to the peri/post-natal Hb switch.Key words: hemoglobin switch, cord blood, cytokines, kit ligand, microRNAs.Citation: Gabbianelli M, Testa U, Morsilli O, Pelosi E, Saulle E, Petrucci E, Castelli G, Giovinazzi S, Mariani G, Fiori ME, Bonanno G, Massa A, Croce CM, Fontana L, and Peschle C. Mechanism of human Hb switching: a possible role of the kit receptor/miR 221-222 complex. Haematologica 2010;95(8):1253-1260. doi:10.3324/haematol.2009

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The postnatal decline of hemoglobin F synthesis in normal full-term infants.

Cited by 94 publications

References 10 publications

Changes in hemoglobin F levels in pregnant women unaffected by clinical fetomaternal hemorrhage

Changes in hemoglobin F levels in pregnant women unaffected by clinical fetomaternal hemorrhage

Proportion of fetal hemoglobin synthesis decreases during erythroid cell maturation.

Mechanism of human Hb switching: a possible role of the kit receptor/miR 221-222 complex

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