Placental gene expression responses to maternal protein restriction in the mouse.
Placental gene expression responses to maternal protein restriction in the mouse.
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DOI：
10.1016/j.placenta.2009.03.002
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发表时间：
2009-05
期刊：
影响因子：
3.8
通讯作者：
Longo, L. D.
中科院分区：
文献类型：
--
作者：
Gheorghe, C. P.;Goyal, R.;Holweger, J. D.;Longo, L. D.
母体蛋白质限制已被证明对胎盘发育有有害影响，并对后代有长期影响。我们测试的假设，通过使用微阵列技术，我们可以确定特定的基因和细胞通路在发展中的胎盘，是响应母体蛋白质剥夺，并提出了一个潜在的机制，观察到的基因表达变化。我们从妊娠后第10.5天（DPC 10.5）至DPC 17.5喂养妊娠FVB/NJ小鼠，这是一种含蛋白质比正常食物少50%的等热量饮食。我们使用Affymble小鼠430A_2.0阵列来测量胎盘中的基因表达变化。我们对调控基因进行了功能注释，并检查了过度代表的功能类别，并进行了通路分析。对于选定的基因，我们通过使用qPCR证实了微阵列结果。我们观察到244个探针组，对应于235个基因，受蛋白质限制性调控（p < 0.001），其中91个基因上调，153个基因下调。上调的基因包括p53信号通路、细胞凋亡、细胞生长负调控因子、细胞代谢负调控因子和表观遗传调控相关基因。下调的基因包括参与核苷酸代谢的基因。微阵列分析使我们能够描述小鼠胎盘中母体蛋白质剥夺的遗传反应。我们观察到，细胞生长和代谢的负调节因子与表观遗传相关的基因一起上调，这表明蛋白质剥夺可能导致应激组织和器官的生长限制和长期表观遗传变化。挑战将是了解这些基因表达反应的细胞和分子机制。
Maternal protein restriction has been shown to have deleterious effects on placental development, and has long-term consequences for the progeny. We tested the hypothesis that, by the use of microarray technology, we could identify specific genes and cellular pathways in the developing placenta that are responsive to maternal protein deprivation, and propose a potential mechanism for observed gene expression changes. We fed pregnant FVB/NJ mice from day post coitum 10.5 (DPC10.5) to DPC17.5, an isocaloric diet containing 50% less protein than normal chow. We used the Affymetrix Mouse 430A_2.0 array to measure gene expression changes in the placenta. We functionally annotated the regulated genes, and examined over-represented functional categories and performed pathway analysis. For selected genes, we confirmed the microarray results by use of qPCR. We observed 244 probe sets, corresponding to 235 genes, regulated by protein restriction (p < 0.001), with ninety-one genes being up-regulated, and 153 down-regulated. Up-regulated genes included those involved in the p53 pathway, apoptosis, negative regulators of cell growth, negative regulators of cell metabolism and genes related to epigenetic control. Down-regulated genes included those involved in nucleotide metabolism. Microarray analysis has allowed us to describe the genetic response to maternal protein deprivation in the mouse placenta. We observed that negative regulators of cell growth and metabolism in conjunction with genes involved in epigenesis were up-regulated, suggesting that protein deprivation may contribute to growth restriction and long-term epigenetic changes in stressed tissues and organs. The challenge will be to understand the cellular and molecular mechanisms of these gene expression responses.
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