Concentration-dependent transcriptome of zebrafish embryo for environmental chemical assessment. (April 2020)

• Record Type: Journal Article
• Authors: Wang, Pingping; Wang, Zhihao; Xia, Pu; Zhang, Xiaowei
• Is Part Of: Chemosphere. Volume 245(2020)
• Publication Date: 2020-04
• Subjects: Omics -- Phenotype-based screen -- Environmental chemicals -- Responsiveness -- Sensitivity -- Mechanistic differentiation; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2019.125632
• Languages: English
• ISSNs: 0045-6535

Abstract

Abstract: Mechanistic information is essential to screen and predict the adverse effects of a large number of chemicals during early-life exposure. Concentration-dependent omics can capture the extent of perturbations of biological pathways or processes and provide information on the mechanism of toxicity. However, the application of concentration-dependent transcriptome to assess the developmental toxicity of environmental chemicals is still limited. Here, twelve chemicals representing five different modes of action (MOAs) were tested by the concentration-dependent reduced zebrafish transcriptome approach (CRZT) in combination with a phenotype-based high content screen (PHCS). The responsiveness, sensitivity and mechanistic differentiation of CRZT were validated in comparison with PHCS. First, PHCS identified 10 chemicals with obvious embryotoxicity (LD50 range: 2.11–70.68 μM), while the potencies of the biological pathways perturbed by 12 chemicals (PODpath20 range: 0.002–2.1 μM) were demonstrated by CRZT. Second, although the potency of the transcriptome perturbations was positively correlated with lethality (LD50 ) (R 2 = 0.64, P-value < 0.05) for most tested chemicals, BbF was non-embryotoxic but was the most potent on the perturbance of biological pathways. Finally, the profiles of the perturbed biological processes and the transcriptome potency (PODpath20 ) captured by CRZT could effectively classify most chemicals corresponding to their known MOAs. In summary, CRZT could significantly improve testing the developmental toxicity of environmental chemicals. Highlights: Concentration dependent transcriptome (CRZT) could classify chemicals. BbF was non-embryotoxic but highly potent on biological pathway perturbance. CRZT improve the ability of prioritizing chemical of phenotype test.