Transcriptomic effects of tributyltin (TBT) in zebrafish eleutheroembryos. A functional benchmark dose analysis

被引:38
作者
Martinez, Ruben [1 ,2 ]
Codina, Anna E. [3 ,4 ]
Barata, Carlos [1 ]
Tauler, Roma [1 ]
Pina, Benjamin [1 ]
Navarro-Martin, Laia [1 ]
机构
[1] IDAEA CSIC, Inst Environm Assessment & Water Res, Barcelona 08034, Catalunya, Spain
[2] Univ Barcelona UB, Barcelona 08007, Catalunya, Spain
[3] Barcelona Inst Sci & Technol BIST, Ctr Genom Regulat CRG, CNAG CRG, Barcelona 08028, Spain
[4] Univ Pompeu Fabra UPF, Barcelona 08003, Spain
基金
欧盟地平线“2020”; 欧洲研究理事会;
关键词
Tributyltin; Zebrafish; Endocrine disruption; RNA-Seq; Benchmark dose; VITAMIN-D-RECEPTOR; ORGANOTIN COMPOUNDS; RNA-SEQ; ENDOCRINE DISRUPTION; NUCLEAR RECEPTORS; GENE-EXPRESSION; PATHWAYS; EXPOSURE; TOOL; CONCORDANCE;
D O I
10.1016/j.jhazmat.2020.122881
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
Exposure to the antifouling tributyltin (TBT) has been related to imposex in mollusks and to obesogenicity, adipogenesis and masculinization in fish. To understand the underlying molecular mechanisms, we evaluated dose-response effects of TBT (1.7-56 nM) in zebrafish eleutheroembryos transcriptome exposed from 2 to 5 days post-fertilization. RNA-sequencing analysis identified 3238 differentially expressed transcripts in eleutheroembryos exposed to TBT. Benchmark dose analyses (BMD) showed that the point of departure (PoD) for transcriptomic effects (9.28 nM) was similar to the metabolomic PoD (11.5 nM) and about one order of magnitude lower than the morphometric PoD (67.9 nM) or the median lethal concentration (LC50: 93.6 nM). Functional analysis of BMD transcriptomic data identified steroid metabolism and cholesterol and vitamin D-3 biosynthesis as the most sensitive pathways to TBT (< 50% PoD). Conversely, transcripts related to general stress and DNA damage became affected only at doses above the PoD. Therefore, our results indicate that transcriptomes can act as early molecular indicators of pollutant exposure, and illustrates their usefulness for the mechanistic identification of the initial toxic events. As the estimated molecular PoDs are close to environmental levels, we concluded that TBT may represent a substantial risk in some natural environments.
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页数:11
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