Zare Ava, Henry Darren, Chua Gordon, Gordon Paul, Habibi Hamid R
Department of Biological Sciences, University of Calgary, Calgary, AB, Canada.
Cumming School of Medicine, Health Sciences Centre, University of Calgary, Calgary, AB, Canada.
Front Endocrinol (Lausanne). 2018 Dec 10;9:749. doi: 10.3389/fendo.2018.00749. eCollection 2018.
Environmental contaminants are known to impair reproduction, metabolism and development in wild life and humans. To investigate the mechanisms underlying adverse effects of contaminants, fathead minnows were exposed to a number of endocrine disruptive chemicals (EDCs) including Nonylphenol (NP), bisphenol-A (BPA), Di(2-ethylhexyl) phthalate (DEHP), and a mixture of the three chemicals for 21 days, followed by determination of the liver transcriptome by expression microarrays. Pathway analysis revealed a distinct mode of action for the individual chemicals and their mixture. The results showed expression changes in over 980 genes in response to exposure to these EDC contaminants individually and in mixture. Ingenuity Pathway core and toxicity analysis were used to identify the biological processes, pathways and the top regulators affected by these compounds. A number of canonical pathways were significantly altered, including cell cycle & proliferation, lipid metabolism, inflammatory, innate immune response, stress response, and drug metabolism. We identified 18 genes that were expressed in all individual and mixed treatments. Relevant candidate genes identified from expression microarray data were verified using quantitative PCR. We were also able to identify specific genes affected by NP, BPA, and DEHP individually, but were also affected by exposure to the mixture of the contaminants. Overall the results of this study provide novel information on the adverse health impact of contaminants tested based on pathway analysis of transcriptome data. Furthermore, the results identify a number of new biomarkers that can potentially be used for screening environmental contaminants.
已知环境污染物会损害野生动物和人类的生殖、新陈代谢及发育。为了探究污染物产生不利影响的潜在机制，将黑头呆鱼暴露于多种内分泌干扰化学物质（EDC）中，包括壬基酚（NP）、双酚A（BPA）、邻苯二甲酸二（2-乙基己基）酯（DEHP）以及这三种化学物质的混合物中21天，随后通过表达微阵列测定肝脏转录组。通路分析揭示了单一化学物质及其混合物的独特作用模式。结果表明，单独或混合暴露于这些EDC污染物会导致980多个基因的表达发生变化。利用Ingenuity Pathway核心分析和毒性分析来确定受这些化合物影响的生物学过程、通路和顶级调控因子。一些经典通路发生了显著改变，包括细胞周期与增殖、脂质代谢、炎症、固有免疫反应、应激反应和药物代谢。我们鉴定出在所有单独和混合处理中均有表达的18个基因。利用定量PCR对从表达微阵列数据中鉴定出的相关候选基因进行了验证。我们还能够鉴定出单独受NP、BPA和DEHP影响，但也受污染物混合物暴露影响的特定基因。总体而言，本研究结果基于转录组数据的通路分析，提供了有关所测试污染物对健康不利影响的新信息。此外，研究结果还鉴定出一些可能用于筛查环境污染物的新生物标志物。
