Ecotoxicogenomics to Support Ecological Risk Assessment: A Case Study with Bisphenol A in Fish

Effects of bisphenol A (BPA) on ovarian transcript profiles as well as targeted end points with endocrine/reproductive relevance were examined in two fish species, fathead minnow (Pimephales promelas) and zebrafish (Danio rerio), exposed in parallel using matched experimental designs. Four days of waterborne exposure to 10 μg BPA/L caused significant vitellogenin induction in both species. However, zebrafish were less sensitive to effects on hepatic gene expression and steroid production than fathead minnow and the magnitude of vitellogenin induction was more modest (i.e., 3-fold compared to 13 000-fold in fathead minnow). The concentration–response at the ovarian transcriptome level was nonmonotonic and violated assumptions that underlie proposed methods for estimating hazard thresholds from transcriptomic results. However, the nonmonotonic profile was consistent among species and there were nominal similarities in the functions associated with the differentially expressed genes, suggesting potential activation of common pathway perturbation motifs in both species. Overall, the results provide an effective case study for considering the potential application of ecotoxicogenomics to ecological risk assessments and provide novel comparative data regarding effects of BPA in fish.

本研究采用匹配的实验设计，对两种鱼类——黑头软口鲦（fathead minnow，学名Pimephales promelas）与斑马鱼（zebrafish，学名Danio rerio）进行平行暴露实验，探究双酚A（bisphenol A，BPA）对其卵巢转录谱以及内分泌/生殖相关靶标终点的影响。经10 μg BPA/L的水体暴露4天后，两种鱼类均出现显著的卵黄蛋白原诱导现象。但相较于黑头软口鲦，斑马鱼对肝脏基因表达与类固醇生成相关影响的敏感性更低，且卵黄蛋白原诱导的幅度更为有限（仅为3倍，而黑头软口鲦可达13000倍）。卵巢转录组层面的浓度-效应关系呈非单调特征，违背了基于转录组学结果估算危害阈值的现有方法所依托的假设前提。不过，两种鱼类的非单调特征谱具有一致性，且差异表达基因所关联的功能存在名义上的相似性，这提示二者可能均激活了共通的通路扰动基序。总体而言，本研究结果为探讨生态毒理基因组学在生态风险评估中的潜在应用提供了一则优质案例，同时也为双酚A对鱼类的影响提供了全新的比较研究数据。