Biosensor zebrafish provide new insights into potential health effects of environmental estrogens.
Biosensor zebrafish provide new insights into potential health effects of environmental estrogens.
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DOI：
10.1289/ehp.1104433
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发表时间：
2012-07
影响因子：
10.4
通讯作者：
Kudoh T
中科院分区：
文献类型：
--
作者：
Lee O;Takesono A;Tada M;Tyler CR;Kudoh T
背景：环境雌激素改变体内的激素信号，可诱导人类和野生动物的生殖异常。现有的雌激素测试系统集中在特定的系统，如生殖。然而，至关重要的是，环境雌激素暴露对各种身体系统产生重大健康影响的可能性可能被忽视了。目的：我们的目的是开发和应用一个敏感的转基因斑马鱼模型，以评估实时影响环境雌激素对信号传导机制在整个身体系统中使用的综合健康评估。研究方法：我们创建了一种新的转基因生物传感器斑马鱼含有一个雌激素诱导型启动子衍生的多个串联雌激素反应元件（ERE）和Gal 4ff-UAS系统增强响应灵敏度。结果如下：使用我们的新的雌激素反应性转基因（TG）斑马鱼，我们确定了环境雌激素的靶组织，这些组织具有非常高的敏感性，即使在环境相关的浓度。TG鱼暴露于雌激素性内分泌干扰物（EDCs）诱导绿色荧光蛋白（GFP）的特异性表达，在各种各样的组织，包括肝脏，心脏，骨骼肌，耳囊，前脑，侧线，神经节，其中大部分还没有建立以前作为目标的雌激素在鱼。此外，我们发现不同的EDCs诱导GFP表达具有不同的组织响应模式和时间轨迹，表明不同的潜在健康影响。总结：我们已经开发了一个强大的新模型，用于了解环境雌激素在脊椎动物中的毒理学效应，机制和健康影响。
Background: Environmental estrogens alter hormone signaling in the body that can induce reproductive abnormalities in both humans and wildlife. Available testing systems for estrogens are focused on specific systems such as reproduction. Crucially, however, the potential for significant health impacts of environmental estrogen exposures on a variety of body systems may have been overlooked. Objective: Our aim was to develop and apply a sensitive transgenic zebrafish model to assess real-time effects of environmental estrogens on signaling mechanisms in a whole body system for use in integrated health assessments. Methods: We created a novel transgenic biosensor zebrafish containing an estrogen-inducible promoter derived with multiple tandem estrogen responsive elements (EREs) and a Gal4ff-UAS system for enhanced response sensitivity. Results: Using our novel estrogen-responsive transgenic (TG) zebrafish, we identified target tissues for environmental estrogens; these tissues have very high sensitivity even at environmentally relevant concentrations. Exposure of the TG fish to estrogenic endocrine-disrupting chemicals (EDCs) induced specific expression of green fluorescent protein (GFP) in a wide variety of tissues including the liver, heart, skeletal muscle, otic vesicle, forebrain, lateral line, and ganglions, most of which have not been established previously as targets for estrogens in fish. Furthermore, we found that different EDCs induced GFP expression with different tissue response patterns and time trajectories, suggesting different potential health effects. Conclusion: We have developed a powerful new model for understanding toxicological effects, mechanisms, and health impacts of environmental estrogens in vertebrates.
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影响因子：
4.8
作者：
Kuiper, GGJM;Lemmen, JG;Gustafsson, JÄ
通讯作者：
Gustafsson, JÄ
影响因子：
2.7
作者：
Froehlicher, Mirjam;Liedtke, Anja;Eggen, Rik I. L.
通讯作者：
Eggen, Rik I. L.
影响因子：
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作者：
Chia VM;Li Y;Quraishi SM;Graubard BI;Figueroa JD;Weber JP;Chanock SJ;Rubertone MV;Erickson RL;McGlynn KA
通讯作者：
McGlynn KA
影响因子：
3.7
作者：
Melzer D;Rice NE;Lewis C;Henley WE;Galloway TS
通讯作者：
Galloway TS
影响因子：
11.8
作者：
Kawakami, K;Takeda, H;Mishina, M
通讯作者：
Mishina, M