The genomic transcriptional response of female fathead minnows (Pimephales promelas) to an acute exposure to the androgen, 17beta-trenbolone.

The genomic transcriptional response of female fathead minnows (Pimephales promelas) to an acute exposure to the androgen, 17beta-trenbolone.
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DOI:
10.1016/j.aquatox.2008.10.002
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发表时间:
2009-01-18
期刊:
Aquatic toxicology (Amsterdam, Netherlands)
影响因子:
--
通讯作者:
Tillitt DE
Tillitt DE
中科院分区:
其他
文献类型:
--
作者:
Dorts J;Richter CA;Wright-Osment MK;Ellersieck MR;Carter BJ;Tillitt DE

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我们研究了雌性黑头呆鱼(Pimephales promelas)对0.1或1.0 μg/L 17β-群勃龙(TB)的急性(4天)暴露的基因组转录反应,TB是一种合成代谢雄激素类固醇的活性代谢产物,用作牛的生长促进剂,也是水生系统中的一种污染物。我们的目标是研究结核病诱导的基因表达谱,确定暴露于结核病的生物标志物,并增加我们对结核病对鱼类繁殖的不利影响的机制的理解。在雌性性腺组织中,使用22 K寡核苷酸微阵列(EcoArray Inc.,盖恩斯维尔,佛罗里达州)显示,响应1 μg TB/L,99个基因显着上调,741个基因显着下调。特别是,羟类固醇(17β)脱氢酶12 a(hsd 17 b12 a)、透明质酸糖蛋白2.2(zp2.2)和激活的STAT,2的蛋白抑制剂(plas 2)在性腺中均下调。在更大的样品组中的Q-PCR测量结果与基因表达中这些变化的方向和幅度的微阵列结果一致。然而,几种新的潜在生物标志物在相同的样品中通过Q-PCR验证,但不能在独立的样品中验证。在肝脏中,Q-PCR测量结果显示卵黄蛋白原1(vtg 1)mRNA的表达显着下降。在脑中,细胞色素P450,家族19,亚家族A,多肽1 B(cyp 19 a1 B,以前称为芳香酶B)转录水平显着降低TB暴露后。我们的研究提供了一个参与介导结核病作用的候选基因,hsd 17 b12 a,以及两个对急性结核病暴露敏感的潜在生物标志物,肝vtg 1和脑cyp 19 a1 b。
We investigated the genomic transcriptional response of female fathead minnows (Pimephales promelas) to an acute (4 day) exposure to 0.1 or 1.0 μg/L of 17β-trenbolone (TB), the active metabolite of an anabolic androgenic steroid used as a growth promoter in cattle and a contaminant of concern in aquatic systems. Our objectives were to investigate the gene expression profile induced by TB, define biomarkers of exposure to TB, and increase our understanding of the mechanisms of adverse effects of TB on fish reproduction. In female gonad tissue, microarray analysis using a 22K oligonucleotide microarray (EcoArray Inc., Gainesville, FL) showed 99 significantly upregulated genes and 741 significantly downregulated genes in response to 1 μg TB/L. In particular, hydroxysteroid (17β) dehydrogenase 12a (hsd17b12a), zona pellucida glycoprotein 2.2 (zp2.2), and protein inhibitor of activated STAT, 2 (pias2) were all downregulated in gonad. Q-PCR measurements in a larger sample set were consistent with the microarray results in the direction and magnitude of these changes in gene expression. However, several novel potential biomarkers were verified by Q-PCR in the same samples, but could not be validated in independent samples. In liver, Q-PCR measurements showed a significant decrease in vitellogenin 1 (vtg1) mRNA expression. In brain, cytochrome P450, family 19, subfamily A, polypeptide 1b (cyp19a1b, previously known as aromatase B) transcript levels were significantly reduced following TB exposure. Our study provides a candidate gene involved in mediating the action of TB, hsd17b12a, and two potential biomarkers sensitive to acute TB exposure, hepatic vtg1 and brain cyp19a1b.
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