Regulation of gene expression in bovine Blastocysts in response to oxygen and the iron chelator desferrioxamine
Regulation of gene expression in bovine Blastocysts in response to oxygen and the iron chelator desferrioxamine
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DOI：
10.1095/biolreprod.106.058826
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发表时间：
2007-07-01
影响因子：
3.6
通讯作者：
Thompson, J. G.
中科院分区：
文献类型：
--
作者：
Harvey, A. J.;Kind, K. L.;Thompson, J. G.
牛囊胚致密化后培养过程中的低氧（2%）条件可提高胚胎质量，并与葡萄糖转运蛋白1（SLC 2A 1）、后期促进复合物（ANAPC 1）和肌营养因子（MTPN）的表达小幅增加相关，表明氧在胚胎发育调控中的作用，通过氧敏感基因表达介导。然而，牛胚胎，至少在囊胚阶段，缺乏可检测水平的氧敏感性基因表达的关键调节因子，缺氧诱导I α（HIHA），而不太好的特点HIF 2 α蛋白是很容易检测。在这里，我们报告说，其他关键HIF 1调节基因的表达模式没有显着改变，在牛囊胚中的氧浓度降低postperfection-with乳酸脱氢酶A（LDHA），这是显着增加后2%的氧文化。抗氧化酶已被认为是潜在的HIF 2靶基因，但它们的表达并没有改变以下低氧培养牛囊胚。此外，去铁胺（铁螯合剂和诱导HIF调控的基因表达）在postcompaction阶段显着增加SLC 2A 1，LDHA，诱导型一氧化氮合酶（NOS 2A），和MTPN基因表达在牛囊胚，虽然发展到囊胚阶段没有显着影响。这些结果进一步表明，基因的表达，已知通过HIF-1在体细胞中的氧调节，是不受氧在植入前压实后牛胚胎发育。牛囊胚中LDHA和SLC 2A 1的氧调节表达表明这些基因的调节可能由HIF 2介导。此外，可以通过使用去铁胺在体外模拟低氧环境对基因表达的影响。这些结果进一步支持了我们的数据，即与体细胞相比，牛囊胚期胚胎对氧的反应是独特的，因为缺乏HIF 1介导的基因表达降低了对低（生理）氧环境的整体反应，这似乎有利于发育。
Low (2%) oxygen conditions during postcompaction culture of bovine blastocysts improve embryo quality and are associated with small increases in the expression of glucose transporter 1 (SLC2A1), anaphase promoting complex (ANAPC1), and myotrophin (MTPN), suggesting a role for oxygen in the regulation of embryo development, mediated through oxygen-sensitive gene expression. However, bovine embryos, to at least the blastocyst stage, lack detectable levels of the key regulator of oxygensensitive gene expression, hypoxia-inducible I alpha (HIHA), while the less well-characterized HIF2 alpha protein is readily detectable. Here we report that other key HIF1 regulated genes are not significantly altered in their expression pattern in bovine blastocysts in response to reduced oxygen concentrations postcompaction-with the exception of lactate dehydrogenase A (LDHA), which was significantly increased following 2% oxygen culture. Antioxidant enzymes have been suggested as potential HIF2 target genes, but their expression was not altered following low-oxygen culture in the bovine blastocyst. The addition of desferrioxamine (an iron chelator and inducer of HIF-regulated gene expression) during postcompaction stages significantly increased SLC2A1, LDHA, inducible nitric oxide synthase (NOS2A), and MTPN gene expression in bovine blastocysts, although development to the blastocyst stage was not significantly affected. These results further suggest that expression of genes, known to be regulated by oxygen via HIF-1 in somatic cells, is not influenced by oxygen during preimplantation postcompaction bovine embryo development. Oxygen-regulated expression of LDHA and SLC2A1 in bovine blastocysts suggests that regulation of these genes may be mediated by HIF2. Furthermore, the effect of a reduced-oxygen environment on gene expression can be mimicked in vitro through the use of desferrioxamine. These results further support our data that the bovine blastocyst stage embryo is unique in its responsiveness to oxygen compared with somatic cells, in that the lack of HIF1-mediated gene expression reduces the overall response to low (physiological) oxygen environments, which appear to favor development.