甲状腺
斑马鱼
生物
转录组
三碘甲状腺素
不良结局途径
激素
生物标志物
计算生物学
内分泌学
基因表达
基因
遗传学
作者
Hannes Reinwald,Azora König,Steve Ayobahan,Julia Alvincz,Levente Şipoş,Bernd Göckener,Gisela Böhle,Orr Shomroni,Henner Hollert,Gabriela Salinas,Christoph Schäfers,Elke Eilebrecht,Sebastian Eilebrecht
标识
DOI:10.1016/j.scitotenv.2020.143914
摘要
Endocrine disruption (ED) can trigger far-reaching effects on environmental populations, justifying a refusal of market approval for chemicals with ED properties. For the hazard assessment of ED effects on the thyroid system, regulatory decisions mostly rely on amphibian studies. Here, we used transcriptomics and proteomics for identifying molecular signatures of interference with thyroid hormone signaling preceding physiological effects in zebrafish embryos. For this, we analyzed the thyroid hormone 3,3′,5-triiodothyronine (T3) and the thyroid peroxidase inhibitor 6-propyl-2-thiouracil (6-PTU) as model substances for increased and repressed thyroid hormone signaling in a modified zebrafish embryo toxicity test. We identified consistent gene expression fingerprints for both modes-of-action (MoA) at sublethal test concentrations. T3 and 6-PTU both significantly target the expression of genes involved in muscle contraction and functioning in an opposing fashion, allowing for a mechanistic refinement of key event relationships in thyroid-related adverse outcome pathways in fish. Furthermore, our fingerprints identify biomarker candidates for thyroid disruption hazard screening approaches. Perspectively, our findings will promote the AOP-based development of in vitro assays for thyroidal ED assessment, which in the long term will contribute to a reduction of regulatory animal tests.
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