Erythroferrone contributes to iron mobilization for embryo erythropoiesis in iron-deficient mouse pregnancies.

Erythroferrone contributes to iron mobilization for embryo erythropoiesis in iron-deficient mouse pregnancies.
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促甲性甲酮有助于铁缺乏小鼠怀孕中的铁动员。

DOI:
10.1002/ajh.26680
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发表时间:
2022-10
影响因子:
12.8
通讯作者:
Nemeth, Elizabeta
Nemeth, Elizabeta
中科院分区:
医学1区
文献类型:
--
作者:
Sangkhae, Veena;Yu, Vivian;Coffey, Richard;O'Brien, Kimberly O.;Ganz, Tomas;Nemeth, Elizabeta

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Erythroferrone(ERFE)是成红细胞分泌的铁代谢调节剂。ERFE的产生在应激红细胞生成期间增加,导致铁调素表达和铁动员减少。怀孕需要铁的可利用性大幅增加,以维持母体红细胞生成扩张和胎儿发育,并且通常受到缺铁的影响。为了确定ERFE在铁充足或缺铁妊娠期间的作用,我们利用表达一系列ERFE水平的小鼠模型:过表达ERFE的转基因小鼠(TG),野生型(WT)和ERFE敲除(KO)小鼠。我们使用低铁或标准铁含量的饮食改变母体铁状态,并在E18.5进行分析。铁缺乏增加WT妊娠的母体ERFE。比较不同的母体基因型,ERFE TG母鼠相对于其肝脏铁负荷具有较低的铁调素,但在任一饮食中与WT母鼠相似的血液学参数。在ERFE KO母鼠中,大多数血液学和铁参数与WT相当,但在两种铁条件下MCV均降低。与母鼠相似,TG胚胎在两种饮食中都具有较低的铁调素,但其血液学参数与WT胚胎没有差异。ERFE KO胚胎在两种饲料中的MCV均低于WT胚胎。在铁缺乏条件下,ERFE KO胚胎具有更高的铁调素、更低的Hb和Hct以及更低的脑铁浓度,与WT胚胎相比,这一作用加剧,表明铁限制。因此,在缺铁条件下,母体和胚胎ERFE促进铁动员胚胎红细胞生成。铁是健康怀孕所必需的。我们研究了铁调节激素erythroferrone(ERFE)在妊娠中的作用,通过比较不同水平ERFE的小鼠的结局。当母鼠缺铁时,胚胎ERFE确保胚胎铁调素被抑制,以促进铁输送到大脑,并产生红细胞将氧气输送到组织。
Erythroferrone (ERFE) is an erythroblast-secreted regulator of iron metabolism. The production of ERFE increases during stress erythropoiesis, leading to decreased hepcidin expression and mobilization of iron. Pregnancy requires a substantial increase in iron availability to sustain maternal erythropoietic expansion and fetal development and is commonly affected by iron deficiency. To define the role of ERFE during iron-replete or iron-deficient pregnancy, we utilized mouse models expressing a range of ERFE levels: transgenic mice overexpressing ERFE (TG), wild-type (WT) and ERFE knockout (KO) mice. We altered maternal iron status using diets with low or standard iron content and performed analysis at E18.5. Iron deficiency increased maternal ERFE in WT pregnancy. Comparing different maternal genotypes, ERFE TG dams had lower hepcidin relative to their liver iron load but similar hematological parameters to WT dams on either diet. In ERFE KO dams, most hematologic and iron parameters were comparable to WT, but MCV was decreased under both iron conditions. Similar to dams, TG embryos had lower hepcidin on both diets, but their hematologic parameters did not differ from those of WT embryos. ERFE KO embryos had lower MCV than WT embryos on both diets. The effect was exacerbated under iron-deficient conditions where ERFE KO embryos had higher hepcidin, lower Hb and Hct and lower brain iron concentration compared to WT embryos, indicative of iron restriction. Thus, under iron-deficient conditions, maternal and embryo ERFE facilitate iron mobilization for embryonic erythropoiesis. Iron is necessary for a healthy pregnancy. We studied the role of the iron-regulatory hormone erythroferrone (ERFE) in pregnancy by comparing outcomes in mice with varying levels of ERFE. When dams were iron-deficient, embryo ERFE ensured embryo hepcidin was suppressed to facilitate iron delivery to the brain and for production of red blood cells to carry oxygen to tissues.
DOI: 10.1038/s41467-021-24333-z
发表时间: 2021-06-29
影响因子: 16.6
作者:
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发表时间: 2014-02-01
影响因子: 7
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发表时间: 2021-06-05
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DOI: 10.1016/j.ejogrb.2005.02.015
发表时间: 2005-10-01
影响因子: 2.6
作者:
Levy, A;Fraser, D;Sheiner, E
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