Sensitive and robust gene expression changes in fish exposed to estrogen--a microarray approach.
Sensitive and robust gene expression changes in fish exposed to estrogen--a microarray approach.
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DOI：
10.1186/1471-2164-8-149
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发表时间：
2007-06-07
期刊：
影响因子：
4.4
通讯作者：
Larsson DG
中科院分区：
文献类型：
--
作者：
Gunnarsson L;Kristiansson E;Förlin L;Nerman O;Larsson DG
卵黄蛋白原是一种公认的鱼类雌激素暴露的生物标志物。然而，在雌激素浓度不足以引起可测量的卵黄蛋白原反应的性腺分化的影响表明，更敏感的生物标志物将是有用的。透明质酸基因的诱导可能更敏感，但它们的特异性并不清楚。本研究的目的是找到额外的敏感和强大的候选生物标志物的雌激素暴露。肝脏mRNA表达谱的特点是青少年虹鳟鱼暴露于0.87和10 ng乙炔基甜菜碱/L的测量浓度使用鲑鱼cDNA微阵列。较高的浓度用于指导随后在不足以诱导卵黄蛋白原的低浓度下鉴定通常更细微的反应。对来自本研究的数据和使用不同鱼种和平台的三个类似微阵列研究的数据进行荟萃分析。在生成的列表中，可能是强大的反应，几个众所周知的雌激素调节基因进行了鉴定。通过定量RT-PCR（qPCR）确认的两个基因符合高灵敏度和稳健性的标准;诱导编码透明质酸蛋白3和核苷二磷酸激酶（nm 23）的基因。跨物种、跨平台的荟萃分析正确地识别出了几个强有力的反应。这增加了我们用于识别候选生物标志物的方法的信心。具体而言，我们建议，分析nm 23基因与透明质酸的基因可能会增加的可能性，以检测暴露于低水平的雌激素化合物在鱼。
Vitellogenin is a well established biomarker for estrogenic exposure in fish. However, effects on gonadal differentiation at concentrations of estrogen not sufficient to give rise to a measurable vitellogenin response suggest that more sensitive biomarkers would be useful. Induction of zona pellucida genes may be more sensitive but their specificities are not as clear. The objective of this study was to find additional sensitive and robust candidate biomarkers of estrogenic exposure. Hepatic mRNA expression profiles were characterized in juvenile rainbow trout exposed to a measured concentration of 0.87 and 10 ng ethinylestradiol/L using a salmonid cDNA microarray. The higher concentration was used to guide the subsequent identification of generally more subtle responses at the low concentration not sufficient to induce vitellogenin. A meta-analysis was performed with data from the present study and three similar microarray studies using different fish species and platforms. Within the generated list of presumably robust responses, several well-known estrogen-regulated genes were identified. Two genes, confirmed by quantitative RT-PCR (qPCR), fulfilled both the criteria of high sensitivity and robustness; the induction of the genes encoding zona pellucida protein 3 and a nucleoside diphosphate kinase (nm23). The cross-species, cross-platform meta-analysis correctly identified several robust responses. This adds confidence to our approach used for identifying candidate biomarkers. Specifically, we propose that analyses of an nm23 gene together with zona pellucida genes may increase the possibilities to detect an exposure to low levels of estrogenic compounds in fish.
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影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
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影响因子：
48
作者：
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通讯作者：
Quackenbush, J
影响因子：
4.4
作者：
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通讯作者：
Iwahashi, Hitoshi