Inconsistent Transcriptomic Responses to Hexabromocyclododecane in Japanese Quail: A Comparative Analysis of Results From Four Different Study Designs.

IF 3.6 4区环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES Environmental Toxicology and Chemistry Pub Date : 2024-07-29 DOI:10.1002/etc.5955

Paul Béziers, Elena Legrand, Emily Boulanger, Niladri Basu, Jessica D Ewald, Paula Henry, Markus Hecker, Jianguo Xia, Natalie Karouna-Renier, Doug Crump, Jessica Head

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Abstract

Efforts to use transcriptomics for toxicity testing have classically relied on the assumption that chemicals consistently produce characteristic transcriptomic signatures that are reflective of their mechanism of action. However, the degree to which transcriptomic responses are conserved across different test methodologies has seldom been explored. With increasing regulatory demand for New Approach Methods (NAMs) that use alternatives to animal models and high-content approaches such as transcriptomics, this type of comparative analysis is needed. We examined whether common genes are dysregulated in Japanese quail (Coturnix japonica) liver following sublethal exposure to the flame retardant hexabromocyclododecane (HBCD), when life stage and test methodologies differ. The four exposure scenarios included one NAM: Study 1-early-life stage (ELS) exposure via a single egg injection, and three more traditional approaches; Study 2-adult exposure using a single oral gavage; Study 3-ELS exposure via maternal deposition after adults were exposed through their diet for 7 weeks; and Study 4-ELS exposure via maternal deposition and re-exposure of nestlings through their diet for 17 weeks. The total number of differentially expressed genes (DEGs) detected in each study was variable (Study 1, 550; Study 2, 192; Study 3, 1; Study 4, 3) with only 19 DEGs shared between Studies 1 and 2. Factors contributing to this lack of concordance are discussed and include differences in dose, but also quail strain, exposure route, sampling time, and HBCD stereoisomer composition. The results provide a detailed overview of the transcriptomic responses to HBCD at different life stages and routes of exposure in a model avian species and highlight certain challenges and limits of comparing transcriptomics across different test methodologies. Environ Toxicol Chem 2024;00:1-11. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

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日本鹌鹑对六溴环十二烷不一致的转录组反应：四种不同研究设计结果的比较分析。

利用转录组学进行毒性测试的努力通常依赖于这样一种假设，即化学品会持续产生反映其作用机制的特征性转录组特征。然而，人们很少探讨不同测试方法的转录组反应在多大程度上是一致的。随着监管部门对使用动物模型和转录组学等高内涵方法以外的新方法（NAM）的需求不断增加，这种类型的比较分析非常必要。我们研究了日本鹌鹑（Coturnix japonica）肝脏在亚致死暴露于阻燃剂六溴环十二烷（HBCD）后，当生命阶段和测试方法不同时，常见基因是否会发生失调。四种暴露情景包括一种营养物质：研究 1--通过单次卵注射进行生命早期阶段（ELS）暴露，以及三种更传统的方法；研究 2--通过单次口服灌胃进行成体暴露；研究 3--在成体通过饮食暴露 7 周后，通过母体沉积进行 ELS 暴露；以及研究 4--通过母体沉积进行 ELS 暴露，并让雏鸟通过饮食再次暴露 17 周。每项研究中检测到的差异表达基因（DEG）总数各不相同（研究1，550个；研究2，192个；研究3，1个；研究4，3个），研究1和研究2中只有19个差异表达基因是相同的。研究讨论了造成这种不一致的因素，包括剂量差异、鹌鹑品系差异、暴露途径差异、采样时间差异以及六溴环十二烷立体异构体成分差异。研究结果提供了鸟类模型物种在不同生命阶段和暴露途径中对六溴环十二烷转录组反应的详细概述，并强调了比较不同测试方法中转录组的某些挑战和限制。环境毒物化学 2024;00:1-11。© 2024 The Author(s).环境毒理学与化学》由 Wiley Periodicals LLC 代表 SETAC 出版。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Environmental Toxicology and Chemistry 环境科学-毒理学

CiteScore

7.40

自引率

9.80%

发文量

265

审稿时长

3.4 months

期刊介绍： The Society of Environmental Toxicology and Chemistry (SETAC) publishes two journals: Environmental Toxicology and Chemistry (ET&C) and Integrated Environmental Assessment and Management (IEAM). Environmental Toxicology and Chemistry is dedicated to furthering scientific knowledge and disseminating information on environmental toxicology and chemistry, including the application of these sciences to risk assessment.[...] Environmental Toxicology and Chemistry is interdisciplinary in scope and integrates the fields of environmental toxicology; environmental, analytical, and molecular chemistry; ecology; physiology; biochemistry; microbiology; genetics; genomics; environmental engineering; chemical, environmental, and biological modeling; epidemiology; and earth sciences. ET&C seeks to publish papers describing original experimental or theoretical work that significantly advances understanding in the area of environmental toxicology, environmental chemistry and hazard/risk assessment. Emphasis is given to papers that enhance capabilities for the prediction, measurement, and assessment of the fate and effects of chemicals in the environment, rather than simply providing additional data. The scientific impact of papers is judged in terms of the breadth and depth of the findings and the expected influence on existing or future scientific practice. Methodological papers must make clear not only how the work differs from existing practice, but the significance of these differences to the field. Site-based research or monitoring must have regional or global implications beyond the particular site, such as evaluating processes, mechanisms, or theory under a natural environmental setting.

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