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利用果蝇蜕皮激素受体活性的体外试验评估环境化学物的内分泌干扰潜力。

Drosophila ecdysone receptor activity-based ex vivo assay to assess the endocrine disruption potential of environmental chemicals.

机构信息

Embryotoxicology Laboratory, Environmental Toxicology Group, CSIR- Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhavan, 31, Mahatma Gandhi Marg, Lucknow, 226001, Uttar Pradesh, India.

Department of Respiratory Medicine, King George's Medical University, Lucknow, 226003, Uttar Pradesh, India.

出版信息

Environ Sci Pollut Res Int. 2022 Aug;29(37):56430-56441. doi: 10.1007/s11356-022-19789-5. Epub 2022 Mar 25.

Abstract

Insect pollinators, critical for both agricultural output and the ecosystem, are declining at an alarming levels partly due to human-made chemicals. Majority of environmental chemicals hamper the endocrine function and studies on the same in insects remain neglected. Here, we report a Drosophila-based ex vivo assay system that employs a reproductive tissue from transgenic males carrying a reporter gene (lacZ) downstream of ecdysone receptor response element (EcRE) and permits the evaluation of chemical-mediated activity modulation of all three isoforms of ecdysone receptor, which are critical for male fertility. We show agonistic [plasticizers, cypermethrin, atrazine, methyl parathion, imidacloprid, cadmium chloride, mercuric chloride or 3-(4-methylbenzylidene) camphor] or antagonistic (apigenin, tributyltin chloride) effects or lack of effect thereof (rutin hydrate, dichlorvos, lead acetate, parabens) for seven different classes of environmental chemicals on ecdysone receptor activity reflecting the specificity and sensitivity of the developed ex vivo assay. Exposure to a few of these chemicals in vivo hampers the fertility of Drosophila males, thus linking the observed endocrine disruption to a quantifiable reproductive phenotype. The developed ex vivo assay offers a quick Drosophila-based screening tool for throughput monitoring of environmental chemicals for their ability to hamper the endocrine function of insect pollinators and other invertebrates.

摘要

昆虫传粉媒介对于农业产出和生态系统都至关重要,但由于人为化学物质的存在,它们正以惊人的速度减少。大多数环境化学物质会干扰内分泌功能,而昆虫内分泌功能方面的研究仍然被忽视。在这里,我们报告了一个基于果蝇的离体检测系统,该系统利用转雄性果蝇的生殖组织,这些雄性果蝇带有一个报告基因(lacZ),位于蜕皮激素受体反应元件(EcRE)下游,从而可以评估所有三种蜕皮激素受体同工型的化学物质介导的活性调节,这对于雄性生育力至关重要。我们展示了(增塑剂、氯菊酯、莠去津、甲基对硫磷、吡虫啉、氯化镉、氯化汞或 3-(4-甲基亚苄基)樟脑)的激动剂或拮抗剂(芹菜素、三丁基锡氯化物)或缺乏作用(芸香苷水合物、敌敌畏、醋酸铅、对羟基苯甲酸酯)对七种不同类别的环境化学物质对蜕皮激素受体活性的影响,反映了所开发的离体检测的特异性和敏感性。体内接触这些化学物质中的几种会损害果蝇雄性的生育能力,从而将观察到的内分泌干扰与可量化的生殖表型联系起来。所开发的离体检测提供了一种快速的基于果蝇的筛选工具,可用于高通量监测环境化学物质对昆虫传粉媒介和其他无脊椎动物内分泌功能的干扰能力。

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