尹晓宇,
周旖妮,
杨景峰,
董武,
内蒙古民族大学动物科学技术学院, 内蒙古自治区毒物监控及毒理学重点实验室, 通辽 028000
作者简介: 李嘉伟(1994-),男,硕士研究生,研究方向为毒理学,E-mail:lijiaweihonor@163.com.
通讯作者: 董武,dongwu@imun.edu.cn
基金项目: 国家自然科学基金资助项目(21267015,81360508,21567019);内蒙古民族大学特色交叉学科群建设项目(MDXK008);内蒙古毒物监控及毒理学重点实验室开放课题项目(MDK2019074);内蒙古民族大学研究生科研创新项目(NMDSS1860)中图分类号: X171.5
BDE-99 and 5-OH-BDE-99 Affect the Pigmentation of the Eyes of Zebrafish Embryos via THRβ
Li Jiawei,Yin Xiaoyu,
Zhou Yini,
Yang Jingfeng,
Dong Wu,
College of Animal Science and Technology, Inner Mongolia University for Nationalities, Inner Mongolia Key Laboratory of Toxicant Monitoring and Toxicology, Tongliao 028000, China
Corresponding author: Dong Wu,dongwu@imun.edu.cn
CLC number: X171.5
-->
摘要
HTML全文
图
参考文献
相关文章
施引文献
资源附件
访问统计
摘要:多溴联苯醚及其羟基代谢物(OH-BDEs)被认为是内分泌干扰物,特别是对甲状腺激素调节的影响。调查并比较了BDE-99及5-OH-BDE-99对甲状腺素受体的影响。斑马鱼胚胎暴露于不同浓度的BDE-99和5-OH-BDE-99中,导致斑马鱼眼球黑色素的色素沉着减少,使用原位杂交以及定量PCR方法检测,发现THRβ在斑马鱼前脑部位表达,并有明显的降低。通过体外实验也证实BDE-99和5-OH-BDE-99能够与THRβ受体结合,尤其是5-OH-BDE-99的结合更为强烈。研究表明,BDE-99和5-OH-BDE-99对斑马鱼胚胎早期THRβ的活性有干扰作用,并导致眼部黑色素沉积减少。上述研究结果对BDE-99和5-OH-BDE-99的生物毒理学机制研究有一定的借鉴意义。
关键词: PBDE/
斑马鱼胚胎/
色素沉着/
THRβ/
BDE-99/
5-OH-BDE-99
Abstract:Polybrominated diphenyl ethers and their hydroxyl metabolites (OH-BDEs) are considered to be endocrine disruptors. They are found in human serum and particularly involved in the regulation of thyroid hormones. The effects of BDE-99 and 5-OH-BDE-99 on the thyroxine receptors were investigated and compared in this study. Zebrafish embryos were exposed to different concentrations of BDE-99 and 5-OH-BDE-99. The results showed that exposure to BDE-99 and 5-OH-BDE-99 resulted in reduced pigmentation in the eyes of zebrafish embryos. In situ hybridization and quantitative PCR analyses revealed that THRβ was expressed in the forebrain and its transcriptional expression was significantly suppressed by the two chemicals. In addition, in vitro experiments demonstrated that BDE-99 and 5-OH-BDE-99 successfully bound to the THRβ receptor. This study indicates that BDE-99 and 5-OH-BDE-99 can disturb the thyroid endocrine system by altering the the expression of THRβ in zebrafish. This study helps better understand the mechanisms of the toxicity of BDE-99 and 5-OH-BDE-99 in zebrafish.
Key words:PBDE/
zebrafish embryos/
pigmentation/
THRβ/
BDE-99/
5-OH-BDE-99.
Zezza D, Tait S, Della Salda L, et al. Toxicological, gene expression and histopathological evaluations of environmentally realistic concentrations of polybrominated diphenyl ethers PBDE-47, PBDE-99 and PBDE-209 on zebrafish embryos[J]. Ecotoxicology and Environmental Safety, 2019, 183:109566 |
McDonald T A. A perspective on the potential health risks of PBDEs[J]. Chemosphere, 2002, 46(5):745-755 |
Giraudo M, Douville M, Letcher R J, et al. Effects of food-borne exposure of juvenile rainbow trout (Oncorhynchus mykiss) to emerging brominated flame retardants 1,2-bis(2,4,6-tribromophenoxy)ethane and 2-ethylhexyl-2,3,4,5-tetrabromobenzoate[J]. Aquatic Toxicology, 2017, 186:40-49 |
Brown F R, Winkler J, Visita P, et al. Levels of PBDEs, PCDDs, PCDFs, and coplanar PCBs in edible fish from California coastal waters[J]. Chemosphere, 2006, 64(2):276-286 |
Rose M, Fernandes A, Mortimer D, et al. Contamination of fish in UK fresh water systems:Risk assessment for human consumption[J]. Chemosphere, 2015, 122:183-189 |
Guo H, Zheng X, Ru S, et al. The leaching of additive-derived flame retardants (FRs) from plastics in avian digestive fluids:The significant risk of highly lipophilic FRs[J]. Journal of Environmental Sciences, 2019, 85:200-207 |
Boyles E, Nielsen C K. PBDEs and dechloranes in raccoons in the Midwestern United States[J]. Bulletin of Environmental Contamination and Toxicology, 2017, 98(6):758-762 |
Chen Y P, Zheng Y J, Liu Q, et al. PBDEs (polybrominated diphenyl ethers) pose a risk to captive giant pandas[J]. Environmental Pollution, 2017, 226:174-181 |
Wemken N, Drage D S, Cellarius C, et al. Emerging and legacy brominated flame retardants in the breast milk of first time Irish mothers suggest positive response to restrictions on use of HBCDD and Penta- and Octa-BDE formulations[J]. Environmental Reseach, 2019, 180:108805 |
Yin S, Guo F, Aamir M, et al. Multicenter biomonitoring of polybrominated diphenyl ethers (PBDEs) in colostrum from China:Body burden profile and risk assessment[J]. Environmental Research, 2019, 179:108828 |
Macaulay L J, Chen A, Rock K D, et al. Developmental toxicity of the PBDE metabolite 6-OH-BDE-47 in zebrafish and the potential role of thyroid receptor beta[J]. Aquatic Toxicology, 2015, 168:38-47 |
Yang J, Zhao H, Chan K M. Toxic effects of polybrominated diphenyl ethers (BDE-47 and 99) and localization of BDE-99 induced cyp1a mRNA in zebrafish larvae[J]. Toxicology Reports, 2017, 4:614-624 |
Chen L, Yu K, Huang C, et al. Prenatal transfer of polybrominated diphenyl ethers (PBDEs) results in developmental neurotoxicity in zebrafish larvae[J]. Environmental & Science Technology, 2012, 46(17):9727-9734 |
Wang F, Fang M, Hinton D E, et al. Increased coiling frequency linked to apoptosis in the brain and altered thyroid signaling in zebrafish embryos (Danio rerio) exposed to the PBDE metabolite 6-OH-BDE-47[J]. Chemosphere, 2018, 198:342-350 |
Linares V, Belles M, Domingo J L. Human exposure to PBDE and critical evaluation of health hazards[J]. Archives of Toxicology, 2015, 89(3):335-356 |
Abolaji A O, Kamdem J P, Lugokenski T H, et al. Involvement of oxidative stress in 4-vinylcyclohexene-induced toxicity in Drosophila melanogaster[J]. Free Radical Biology and Medicine, 2014, 71:99-108 |
Balch G C, Velez-Espino L A, Sweet C, et al. Inhibition of metamorphosis in tadpoles of Xenopus laevis exposed to polybrominated diphenyl ethers (PBDEs)[J]. Chemosphere, 2006, 64(2):328-338 |
Macaulay L J, Chernick M, Chen A, et al. Exposure to a PBDE/OH-BDE mixture alters juvenile zebrafish (Danio rerio) development[J]. Environmental Toxicology and Chemistry, 2017, 36(1):36-48 |
Levy-Bimbot M, Major G, Courilleau D, et al. Tetrabromobisphenol-A disrupts thyroid hormone receptor alpha function in vitro:Use of fluorescence polarization to assay corepressor and coactivator peptide binding[J]. Chemosphere, 2012, 87(7):782-788 |
Dong W, Macaulay L J, Kwok K W, et al. The PBDE metabolite 6-OH-BDE-47 affects melanin pigmentation and THRβ mRNA expression in the eye of zebrafish embryos[J]. Endocrine Disruptors, 2014, 2(1):e969072 |
Zheng J, Hashimoto A, Putnam M, et al. Development of a thyroid hormone receptor targeting conjugate[J]. Bioconjugate Chemistry, 2008, 19(6):1227-1234 |
Benvenuti S, Luciani P, Cellai I, et al. Thyroid hormones promote cell differentiation and up-regulate the expression of the seladin-1 gene in in vitro models of human neuronal precursors[J]. Journal of Endocrinology, 2008, 197(2):437-446 |
Xing W, Govoni K E, Donahue L R, et al. Genetic evidence that thyroid hormone is indispensable for prepubertal insulin-like growth factor-I expression and bone acquisition in mice[J]. Journal of Bone and Mineral Research, 2012, 27(5):1067-1079 |
Helbing C C, Bailey C M, Ji L, et al. Identification of gene expression indicators for thyroid axis disruption in a Xenopus laevis metamorphosis screening assay. Part 1. Effects on the brain[J]. Aquatic Toxicology, 2007, 82(4):227-241 |
Argumedo G S, Sanz C R, Olguin H J. Experimental models of developmental hypothyroidism[J]. Hormone Metabolic Research, 2012, 44(2):79-85 |
Rivas M, Naranjo J R. Thyroid hormones, learning and memory[J]. Genes Brain and Behavior, 2007, 6(1):40-44 |
Azadi S, Zhang Y, Caffe A R, et al. Thyroid-beta2 and the retinoid RAR-alpha, RXR-gamma and ROR-beta2 receptor mRNAs; expression profiles in mouse retina, retinal explants and neocortex[J]. Neuroreport, 2002, 13(6):745-750 |
Xing W, Aghajanian P, Goodluck H, et al. Thyroid hormone receptor-beta1 signaling is critically involved in regulating secondary ossification via promoting transcription of the Ihh gene in the epiphysis[J]. American Journal of Physiology Endocrinology and Metabolism, 2016, 310(10):E846-E854 |
Arbogast P, Flamant F, Godement P, et al. Thyroid hormone signaling in the mouse retina[J]. PLoS One, 2016, 11(12):e0168003 |
Jones I, Srinivas M, Ng L, et al. The thyroid hormone receptor beta gene:Structure and functions in the brain and sensory systems[J]. Thyroid, 2003, 13(11):1057-1068 |
Carlsson G, Kulkarni P, Larsson P, et al. Distribution of BDE-99 and effects on metamorphosis of BDE-99 and -47 after oral exposure in Xenopus tropicalis[J]. Aquatic Toxicology, 2007, 84(1):71-79 |
Wu L, Li Y, Ru H, et al. Parental exposure to 2,2',4,4'5-pentain polybrominated diphenyl ethers (BDE-99) causes thyroid disruption and developmental toxicity in zebrafish[J]. Toxicology Applied Pharmacology, 2019, 372:11-18 |