Processes underlying the nutritional programming of embryonic development by iron deficiency in the rat.
Processes underlying the nutritional programming of embryonic development by iron deficiency in the rat.
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DOI：
10.1371/journal.pone.0048133
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Langley-Evans SC
中科院分区：
文献类型：
--
作者：
Swali A;McMullen S;Hayes H;Gambling L;McArdle HJ;Langley-Evans SC
缺铁是一个全球性的健康问题，在一定程度上影响了世界三分之二的人口。这是发达国家和发展中国家孕妇的一个特殊问题。喂养妊娠大鼠缺铁的饮食与成年雄性后代的高血压和肾单位捐赠减少有关。然而，从铁缺乏到胎儿肾脏发育的机制途径仍然是难以捉摸的。本研究旨在通过评估大鼠胚胎中基因和蛋白质表达的变化，建立与铁缺乏相关的潜在过程，重点关注营养损伤时发生的反应。微阵列数据分析显示，子宫内缺铁导致雄性大鼠胚胎（d13）中979个基因显著上调，1545个基因下调。与这些基因相关的受影响的过程包括有丝分裂的启动，BAD介导的细胞凋亡，RNA聚合酶II preinitiation复合物和WNT信号的装配。蛋白质组学分析突出显示了7种蛋白质，其在铁缺乏时表现出显著的上调，11种蛋白质下调。这些关键蛋白的主要功能包括细胞增殖、蛋白质转运和折叠、细胞骨架重塑和蛋白酶体复合物。与我们最近的工作一致，我们认为蛋白酶体复合物的扰动是对子宫内营养不良的普遍反应，我们认为缺铁单独导致更具体的蛋白质折叠和运输失败。这种微妙的质量控制系统的失衡可能导致细胞功能障碍和凋亡。因此，这些研究结果提供了一个深入了解与胚胎发育相关的潜在机制，在铁状态差的条件下，其在成年生活中的健康。
Poor iron status is a global health issue, affecting two thirds of the world population to some degree. It is a particular problem among pregnant women, in both developed and developing countries. Feeding pregnant rats a diet deficient in iron is associated with both hypertension and reduced nephron endowment in adult male offspring. However, the mechanistic pathway leading from iron deficiency to fetal kidney development remains elusive. This study aimed to establish the underlying processes associated with iron deficiency by assessing gene and protein expression changes in the rat embryo, focussing on the responses occurring at the time of the nutritional insult. Analysis of microarray data showed that iron deficiency in utero resulted in the significant up-regulation of 979 genes and down-regulation of 1545 genes in male rat embryos (d13). Affected processes associated with these genes included the initiation of mitosis, BAD-mediated apoptosis, the assembly of RNA polymerase II preinitiation complexes and WNT signalling. Proteomic analyses highlighted 7 proteins demonstrating significant up-regulation with iron deficiency and the down-regulation of 11 proteins. The main functions of these key proteins included cell proliferation, protein transport and folding, cytoskeletal remodelling and the proteasome complex. In line with our recent work, which identified the perturbation of the proteasome complex as a generalised response to in utero malnutrition, we propose that iron deficiency alone leads to a more specific failure in correct protein folding and transport. Such an imbalance in this delicate quality-control system can lead to cellular dysfunction and apoptosis. Therefore these findings offer an insight into the underlying mechanisms associated with the development of the embryo during conditions of poor iron status, and its health in adult life.
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影响因子：
20.3
作者：
Hakobyan, N;Kazarian, T;Valentino, LA
通讯作者：
Valentino, LA
影响因子：
158.5
作者：
Barker, DJP;Osmond, C;Eriksson, JG
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Bennis-Taleb, N;Remacle, C;Reusens, B
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Reusens, B
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LAI, AC;KIYOMIITO, M;NIIYAMA, Y
通讯作者：
NIIYAMA, Y
影响因子：
3.7
作者：
Bogdarina I;Haase A;Langley-Evans S;Clark AJ
通讯作者：
Clark AJ