母体暴露环境浓度盐酸四环素对F1代斑马鱼胚胎骨骼发育的影响
Parental Tetracycline Hydrochloride Exposure and Resultant Offspring Cartilage Toxicity
-
摘要: 抗生素被广泛应用于兽药和饲料添加剂中，尤其是四环素等广谱抗生素，长期滥用于养殖业中。四环素是目前用量最大、应用范围最广泛的一种抗生素。抗生素在体内蓄积，或者以原型随粪便排入环境中，造成环境污染。实验用斑马鱼为模式动物来评价低浓度四环素对斑马鱼下一代（F1）发育的毒性影响。选取4月龄亲代斑马鱼（F0），分别给予0.1、1和100 μg·L-1盐酸四环素（tetracycline hydrochloride，TCH）处理30 d后，实施交配后获得F1代斑马鱼胚胎。结果表明，F1代胚胎随母体TCH暴露浓度的升高而孵化率降低、畸形率和死亡率增加。同时斑马鱼幼鱼下颌骨长度、下颌弓长度变长、下颌骨宽度和舌骨角长度缩短。进一步检测与幼鱼骨骼发育相关基因表达，发现TCH抑制了runx1、sox9a、sox10和col2α1a mRNA的表达。以上研究结果表明，TCH的残留和污染可能会影响斑马鱼胚胎的发育，尤其是对胚胎软骨发育有影响。Abstract: Antibiotics are widely used as veterinary drugs and feed additives, especially for broad-spectrum antibiotics such as tetracycline, which have been abused in the breeding industry. Tetracycline is the antibiotics with the largest dosage and the widest application. Antibiotics accumulate in the body or are excreted into the environment via feces as a prototype, causing environmental pollution. This experiment used zebrafish as a model organism to evaluate the effects of low concentration of tetracycline on the transgenerational (F1) zebrafish. Parent zebrafish (F0, approximantely 4-month-old) were exposed to 0.1, 1 and 100 μg·L-1 of tetracycline hydrochloride (TCH) for 30 d. The F1 generation zebrafish embryos were obtained. The results showed that the F1 generation embryos had a decreased hatching rate and an increased malformation rate and mortality rate, all of which were concentration-dependent. In addition, the zebrafish juvenile had longer mandible and mandibular arch and more narrow mandible and shorter hyoid bone. Furthermore, transcriptional expression of runx1, sox9a, sox10 and col2α1a (genes related to skeletal development of juvenile fish) were inhibited by exposure to TCH. This study demonstrates that TCH showed a transgenerational effect by affecting the development of zebrafish embryos, especially the development of embryonic cartilage.
-
Key words:
- tetracycline hydrochloride /
- zebrafish embryo /
- F1 generation /
- toxicity /
- cartilage development
-
-
Faria M, Lopez M A, Fernandez-Sanjuan M, et al. Comparative toxicity of single and combined mixtures of selected pollutants among larval stages of the native freshwater mussels (Unio elongatulus) and the invasive zebra mussel (Dreissena polymorpha)[J]. Science of the Total Environment, 2010, 408(12):2452-2458 Boxall A B, Fogg L A, Blackwell P A, et al. Veterinary medicines in the environment[J]. Reviews of Environmental Contamination and Toxicology, 2004, 180:1-91 魏维芮. 浅谈我国抗生素的滥用问题及对策[J]. 化工管理, 2018(3):92, 94 Ben W, Qiang Z, Adams C, et al. Simultaneous determination of sulfonamides, tetracyclines and tiamulin in swine wastewater by solid-phase extraction and liquid chromatography-mass spectrometry[J]. Journal of Chromatography A, 2008, 1202(2):173-180 徐永刚, 宇万太, 马强, 等. 环境中抗生素及其生态毒性效应研究进展[J]. 生态毒理学报, 2015, 10(3):11-27 Xu Y G, Yu W T, Ma Q, et al. The antibiotic in environment and its ecotoxicity:A review[J]. Asian Journal of Ecotoxicology, 2015, 10(3):11-27(in Chinese)
雷慧宁. 规模化猪场废水处理工艺中抗生素和重金属残留及其生态风险[D]. 上海:华东师范大学, 2016:26 Lei H N. Antibiotic and heavy metal residues and ecological risks in large-scale pig farm wastewater treatment process[D]. Shanghai:East China Normal University, 2016:26(in Chinese) Yu X, Wu Y, Deng M, et al. Tetracycline antibiotics as PI3K inhibitors in the Nrf2-mediated regulation of antioxidative stress in zebrafish larvae[J]. Chemosphere, 2019, 226:696-703 Meyer M T, Bumgarner J E, Varns J L, et al. Use of radioimmunoassay as a screen for antibiotics in confined animal feeding operations and confirmation by liquid chromatography/mass spectrometry[J]. Science of the Total Environment, 2000, 248(2-3):181-187 Keerthisinghe T P, Wang F, Wang M, et al. Long-term exposure to TET increases body weight of juvenile zebrafish as indicated in host metabolism and gut microbiome[J]. Environment Internationnal, 2020, 139:105705 Qiu W, Sun J, Fang M, et al. Occurrence of antibiotics in the main rivers of Shenzhen, China:Association with antibiotic resistance genes and microbial community[J]. Science of the Total Environment, 2019, 653:334-341 Yuan J, Ni M, Liu M, et al. Occurrence of antibiotics and antibiotic resistance genes in a typical estuary aquaculture region of Hangzhou Bay, China[J]. Marine Pollution Bulletin, 2019, 138:376-384 Zhu Y G, Johnson T A, Su J Q, et al. Diverse and abundant antibiotic resistance genes in Chinese swine farms[J]. Proceedings of the National Academy of Sciences of the United States of America, 2013, 110(9):3435-3440 Franco G C, Kajiya M, Nakanishi T, et al. Inhibition of matrix metalloproteinase-9 activity by doxycycline ameliorates RANK ligand-induced osteoclast differentiation in vitro and in vivo[J]. Experimental Cell Research, 2011, 317(10):1454-1464 Kim Y, Kim J, Lee H, et al. Tetracycline analogs inhibit osteoclast differentiation by suppressing MMP-9-mediated histone H3 cleavage[J]. International Journal of Molecular Sciences, 2019, 20(16):4038 Dorman G, Cseh S, Hajdu I, et al. Matrix metalloproteinase inhibitors:A critical appraisal of design principles and proposed therapeutic utility[J]. Drugs, 2010, 70(8):949-964 Vandooren J, Knoops S, Aldinucci Buzzo J L, et al. Differential inhibition of activity, activation and gene expression of MMP-9 in THP-1 cells by azithromycin and minocycline versus bortezomib:A comparative study[J]. PLoS One, 2017, 12(4):e0174853 Dong W, Hinton D E, Kullman S W. TCDD disrupts hypural skeletogenesis during medaka embryonic development[J]. Toxicological Sciences, 2012, 125(1):91-104 Zhang G, Eames B F, Cohn M J. Chapter 2. Evolution of vertebrate cartilage development[J]. Current Topics in Developmental Biology, 2009, 86:15-42 Karsenty G. Transcriptional control of skeletogenesis[J]. Annual Review of Genomics and Human Genetics, 2008, 9:183-196 Flores M V, Lam E Y, Crosier P, et al. A hierarchy of Runx transcription factors modulate the onset of chondrogenesis in craniofacial endochondral bones in zebrafish[J]. Developmental Dynamics, 2006, 235(11):3166-3176 Enomoto H, Furuichi T, Zanma A, et al. Runx2 deficiency in chondrocytes causes adipogenic changes in vitro[J]. Journal of Cell Science, 2004, 117:417-425 Bell D M, Leung K K, Wheatley S C, et al. SOX9 directly regulates the type-Ⅱ collagen gene[J]. Nature Genetics, 1997, 16(2):174-178 Lefebvre V, Huang W, Harley V R, et al. SOX9 is a potent activator of the chondrocyte-specific enhancer of the pro alpha1(Ⅱ) collagen gene[J]. Molecular and Cellular Biology, 1997, 17(4):2336-2346 Sekiya I, Tsuji K, Koopman P, et al. SOX9 enhances aggrecan gene promoter/enhancer activity and is up-regulated by retinoic acid in a cartilage-derived cell line, TC6[J]. The Journal of Biological Chemistry, 2000, 275(15):10738-10744 Bridgewater L C, Lefebvre V, de Crombrugghe B. Chondrocyte-specific enhancer elements in the Col11a2 gene resemble the Col2a1 tissue-specific enhancer[J]. The Journal of Biological Chemistry, 1998, 273(24):14998-15006 Goldring M B, Peng H, Ijiri K, et al. ESE1 inhibits COL2A1 promoter activity via Sox9 and CBP[J]. Matrix Biology, 2006, 25(S1):S90 何加发. 诺氟沙星对稀有鮈鲫雌性亲本胚胎及子代骨骼发育的影响[D]. 杨凌:西北农林科技大学, 2019:1 He J F. The influence of embryo and bone development treated with norfloxacin in rare minnow Gobiocypris rarus offspring[D]. Yangling:Northwest A&F University, 2019:1(in Chinese) Crump J G, Swartz M E, Eberhart J K, et al. Moz-dependent Hox expression controls segment-specific fate maps of skeletal precursors in the face[J]. Development, 2006, 133(14):2661-2669 Dutton J R, Antonellis A, Carney T J, et al. An evolutionarily conserved intronic region controls the spatiotemporal expression of the transcription factor Sox10[J]. BMC Developmental Biology, 2008, 8:105 Halpern M E, Hatta K, Amacher S L, et al. Genetic interactions in zebrafish midline development[J]. Developmental Biology, 1997, 187(2):154-170 Renn J, Winkler C, Schartl M, et al. Zebrafish and medaka as models for bone research including implications regarding space-related issues[J]. Protoplasma, 2006, 229(2-4):209-214 Brannen K C, Panzica-Kelly J M, Danberry T L, et al. Development of a zebrafish embryo teratogenicity assay and quantitative prediction model[J]. Birth Defects Research Part B, Developmental and Reproductive Toxicology, 2010, 89(1):66-77 Dong W, Wang F, Fang M, et al. Use of biological detection methods to assess dioxin-like compounds in sediments of Bohai Bay, China[J]. Ecotoxicology and Environmental Safety, 2019, 173:339-346 Osman A G, Wuertz S, Mekkawy I A, et al. Lead induced malformations in embryos of the African catfish Clarias gariepinus (Burchell, 1822)[J]. Environmental Toxicology, 2007, 22(4):375-389 梁伟放, 赵建国, 柳贤德. 四环素对斑马鱼胚胎发育及CAT和SOD活性的影响[J]. 热带农业工程, 2017, 41(1):17-20 Liang W F, Zhao J G, Liu X D, et al. Effect of tetracycline on zebrafish embryonic development and CAT and SOD activities[J]. Tropical Agricultural Engineering, 2017, 41(1):17-20(in Chinese)
Jonsson M E, Kubota A, Timme-Laragy A R, et al. Ahr2-dependence of PCB126 effects on the swim bladder in relation to expression of CYP1 and cox-2 genes in developing zebrafish[J]. Toxicology and Applied Pharmacology, 2012, 265(2):166-174 Yabe K, Satoh H, Ishii Y, et al. Early pathophysiologic feature of arthropathy in juvenile dogs induced by ofloxacin, a quinolone antimicrobial agent[J]. Veterinary Pathology, 2004, 41(6):673-681 Goto K, Yabe K, Suzuki T, et al. Chondrotoxicity and toxicokinetics of novel quinolone antibacterial agents DC-159a and DX-619 in juvenile rats[J]. Toxicology, 2010, 276(2):122-127 Bi W, Deng J M, Zhang Z, et al. Sox9 is required for cartilage formation[J]. Nature Genetics, 1999, 22(1):85-89 Akiyama H, Chaboissier M C, Martin J F, et al. The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6[J]. Genes & Development, 2002, 16(21):2813-2828 Cheah K S, Au P K, Lau E T, et al. The mouse Col2a-1 gene is highly conserved and is linked to Int-1 on chromosome 15[J]. Mammalian Genome, 1991, 1(3):171-183 Wood A, Ashhurst D E, Corbett A, et al. The transient expression of type Ⅱ collagen at tissue interfaces during mammalian craniofacial development[J]. Development, 1991, 111(4):955-968 Li S W, Khillan J, Prockop D J. The complete cDNA coding sequence for the mouse pro alpha 1(Ⅰ) chain of type Ⅰ procollagen[J]. Matrix Biology, 1995, 14(7):593-595 Cheah K S, Lau E T, Au P K, et al. Expression of the mouse alpha 1(Ⅱ) collagen gene is not restricted to cartilage during development[J]. Development, 1991, 111(4):945-953 -
点击查看大图
计量
- 文章访问数: 2329
- HTML全文浏览数: 2329
- PDF下载数: 69
- 施引文献: 0
下载:
