Integrated thyroid endocrine disrupting effect on zebrafish (Danio rario) larvae via simultaneously repressing type II iodothyronine deiodinase and activating thyroid receptor-mediated signaling following waterborne exposure to trace azocyclotin. (December 2019)

• Record Type: Journal Article
• Authors: Jiao, Fang; Qiao, Kun; Jiang, Yao; Li, Shuying; Zhao, Jinghao; Gui, Wenjun
• Is Part Of: Environmental pollution. Volume 255(2019)Part 2
• Publication Date: 2019-12
• Subjects: Azocyclotin -- Zebrafish -- Thyroid endocrine disruption -- Deiodinase -- TR-Mediated signaling; Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2019.113328
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: As a widely used organotin acaricide nowadays, azocyclotin (ACT) could induce thyroidal endocrine disruption in fishes and amphibians, but its dominant disrupting mode remains unknown. In this study, zebrafish were firstly exposed to ACT (0.18–0.36 ng/mL) from 2 hpf (hours post fertilization) to 30 dpf (days post fertilization), and a series of developmental toxicological endpoints and thyroid hormones were measured. Result showed that no developmental toxicity to zebrafish was found in 0.18 and 0.24 ng/mL groups except decreased body weight (30 dpf, 0.24 ng/mL). However, exposed to 0.36 ng/mL ACT led to reductions in heartbeat (48 hpf), hatching rate (72 hpf) and bodyweight (30 dpf). General tendencies of decreases in free T3 but increases in free T4 and reductions in ratio of free T3/T4 were also found, inferring that type II deiodinase (Dio2) was repressed. This inference was confirmed by Western analysis that Dio2 expression reduced by 42.7% after 0.36 ng/mL ACT treatment. Moreover, RNA-Seq analysis implied that exposed to 0.36 ng/mL ACT altered the genome-wide gene expression profiles of zebrafish. Totally 5660 genes (involving 3154 down-regulated and 2596 up-regulated genes) were differentially expressed, and 13 deferentially expressed genes including down-regulated dio2 were significantly enriched in thyroid hormone signaling pathway. Subsequently, an in vitro thyroid receptor-reporter gene assay using GH3 cells was performed to further explore the potential disrupting mechanism. Result showed that luciferase activity slightly increased after exposure to ACT alone or ACT combined with low level T3, but was suppressed when combined with high level T3. It indicted there probably existed a competitive relationship in some extent between ACT and T3 in vivo . Overall, the present study provided preliminary evidences that long-term exposure to trace ACT repressed Dio2 expression, declined T3 and then activated thyroid receptor-mediated signaling, thereby leading to integrated thyroid endocrine disruption in zebrafish larvae. Graphical abstract: Image 1 Highlights: Azocyclotin caused developmental and thyroid endocrine toxicities on zebrafish larvae. Azocyclotin caused increase in T4 but decrease in T3 in zebrafish larvae. RNA-Seq analysis suggested azocyclotin disrupted thyroid hormone signaling pathway. Western blotting indicated azocyclotin repressed Dio2 expression in zebrafish larvae. Azocyclotin in vivo bound RXR to activate TR-mediated signaling as a T3 antagonist. Abstract : Azocyclotin distinctly reduced T3 via repressing Dio2 expression, subsequently activated TR-mediated signaling, thereby inducing integrated thyroid endocrine disruption in larva1zebrafish.