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左炔诺孕酮对稀有鮈鲫脂质代谢的干扰效应
Disrupting effects of levonorgestrel on lipid metabolism in Chinese rare minnow
为探究孕激素左炔诺孕酮（LNG）对鱼类脂质代谢的影响，将刚孵化的稀有鮈鲫仔鱼置于0.8和6.5ng/L LNG暴露6个月至性成熟，考察其生长指标、肝脏组织病理学变化、脂质和脂蛋白含量及脂质代谢相关基因的表达情况.结果显示：（1）0.8，6.5ng/L LNG暴露显著降低70dph稀有鮈鲫的体重和肥满度，且6.5ng/L LNG暴露显著降低180dph雌、雄鱼的体长或体重；（2）0.8，6.5ng/L LNG暴露导致180dph成鱼肝脏出现细胞空泡、肝细胞肿胀等损伤；（3）0.8，6.5ng/L LNG暴露显著降低180dph雌鱼肝脏中甘油三酯、胆固醇的含量，且6.5ng/L LNG暴露显著降低雌鱼血浆中甘油三酯的含量，但对雄鱼肝脏及血浆的脂质含量无显著影响；（4）0.8，6.5ng/L LNG暴露显著降低180dph雌鱼肝脏中脂肪酸合成酶基因（fasn） mRNA的表达水平，且6.5ng/L LNG暴露显著降低180dph雄鱼肝脏中fasn及乙酰辅酶A羧化酶基因（acaca） mRNA的表达水平.由此可见，LNG长期低剂量暴露可抑制稀有鮈鲫的生长、诱导肝细胞损伤、引起肝脏和血浆脂质含量发生性别差异性变化，并影响肝脏中脂质代谢相关基因的表达，表明LNG在低浓度下可干扰稀有鮈鲫的脂质代谢，提示LNG对鱼类种群具有较高的潜在生态风险.
In order to explore the effects of progestin levonorgestrel (LNG) on lipid metabolism in fish, newly hatched Chinese rare minnow larvae were exposed to 0.8 and 6.5ng/L LNG for 6months until adults, and the growth parameters, hepatic histopathologic changes, lipids and lipoproteins contents and expression levels of lipid metabolism related genes were investigated. The results showed that the body weights and condition factors of rare minnow at 70dph were significantly decreased by exposure to 0.8 and 6.5ng/L LNG, and the body lengths or body weights were also significantly decreased in females and males at 180dph after exposure to 6.5ng/L LNG. Hepatic damages such as cellular vacuolation and swelling of hepatocytes were induced in adults at 180dph after exposure to 0.8 and 6.5ng/L LNG. The hepatic triglyceride and cholesterol contents in females at 180dph were significantly decreased by exposure to 0.8 and 6.5ng/L LNG, and the serum triglyceride contents were also significantly decreased after exposure to 6.5ng/L LNG, but no effects were observed on male hepatic and serum lipid contents. Besides, the hepatic mRNA expression level of fatty acid synthase gene (fasn) was significantly decreased in females at 180dph by exposure to 0.8 and 6.5ng/L LNG, and the hepatic mRNA expression levels of fasn and acetyl-CoA carboxylase gene (acaca) were also significantly decreased in males at 180dph after exposure to 6.5ng/L LNG. As can be concluded from the results, long-term exposure of rare minnow to low concentrations of LNG inhibited growth, induced hepatic damages, caused sex-specific changes on hepatic and serum lipid contents, and affected mRNA expression of lipid metabolism related genes in the liver. The present study demonstrates that LNG could disrupt lipid metabolism in rare minnow at low concentrations, indicating high potential ecological risks of LNG to fish populations.
长期暴露 / 稀有鮈鲫 / 孕激素 / 脂质代谢 / 左炔诺孕酮
Chinese rare minnow / levonorgestrel / lipid metabolism / long-term exposure / progestin
[1] Fent K. Progestins as endocrine disrupters in aquatic ecosystems:Concentrations, effects and risk assessment[J]. Environment International, 2015,84:115-130.
[2] Kumar V, Johnson A C, Trubiroha A, et al. The challenge presented by progestins in ecotoxicological research:a critical review[J]. Environmental Science & Technology, 2015,49:2625-2638.
[3] Lopez de Alda M J, Gil A, Paz E, et al. Occurrence and analysis of estrogens and progestogens in river sediments by liquid chromatography-electrospray-mass spectrometry[J]. Analyst, 2002,127:1299-1304.
[4] Vulliet E, Wiest L, Baudot R, et al. Multi-residue analysis of steroids at sub-ng/L levels in surface and ground-waters using liquid chromatography coupled to tandem mass spectrometry[J]. Journal of Chromatography A, 2008,1210:84-91.
[5] Liu S, Ying G G, Zhao J L, et al. Trace analysis of 28steroids in surface water, wastewater and sludge samples by rapid resolution liquid chromatography-electrospray ionization tandem mass spectrometry[J]. Journal of Chromatography A, 2011,1218:1367-1378.
[6] Yarahmadi H, Duy S V, Hachad M, et al. Seasonal variations of steroid hormones released by wastewater treatment plants to river water and sediments:Distribution between particulate and dissolved phases[J]. Science of the Total Environment, 2018,635:144-155.
[7] Al-Odaini N A, Zakaria M P, Yaziz M I, et al. Occurrence of synthetic hormones in sewage effluents and Langat River and its tributaries. Malaysia[J]. International Journal of Environmental Analytical Chemistry, 2013,93:1457-1469.
[8] Zeilinger J, Steger-Hartmann T, Maser E, et al. Effects of synthetic gestagens on fish reproduction[J]. Environmental Toxicology and Chemistry, 2009,28(12):2663-2670.
[9] Runnalls T J, Beresford N, Losty E, et al. Several synthetic progestins with different potencies adversely affect reproduction of fish[J]. Environmental Science & Technology, 2013,47:2077-2084.
[10] Kroupova H K, Trubiroha A, Lorenz C, et al. The progestin levonorgestrel disrupts gonadotropin expression and sex steroid levels in pubertal roach (Rutilus rutilus)[J]. Aquatic Toxicology, 2014,154:154-162.
[11] Frankel T, Yonkos L, Frankel J. Exposure effects of levonorgestrel on oogenesis in the fathead minnow (Pimephales promelas)[J]. Environmental Toxicology and Chemistry, 2017,36(12):3299-3304.
[12] Frankel T, Yonkos L, Ampy F, et al. Exposure to levonorgestrel increases nest acquisition success and decreases sperm motility in the male fathead minnow (Pimephales promelas)[J]. Environmental Toxicology and Chemistry, 2018,37(4):1131-1137.
[13] Ellestad L E, Cardon M, Chambers I G, et al. Environmental gestagens activate fathead minnow (Pimephales promelas) nuclear progesterone and androgen receptors in vitro[J]. Environmental Science & Technology, 2014,48(14):8179-8187.
[14] Bain P A, Kumar A, Ogino Y, et al. Nortestosterone-derived synthetic progestogens do not activate the progestogen receptor of Murray-Darling rainbowfish (Melanotaenia fluviatilis) but are potent agonists of androgen receptors alpha and beta[J]. Aquatic Toxicology, 2015,163:97-101.
[15] Brockmeier E K, Scott P D, Denslow N D, et al. Transcriptomic and physiological changes in eastern mosquitofish (Gambusia holbrooki) after exposure to progestins and anti-progestagens[J]. Aquatic Toxicology, 2016,179:8-17.
[16] Hua J, Han J, Guo Y, et al. The progestin levonorgestrel affects sex differentiation in zebrafish at environmentally relevant concentrations[J]. Aquatic Toxicology, 2015,166:1-9.
[17] Svensson J, Mustafa A, Fick J, et al. Developmental exposure to progestins causes male bias and precocious puberty in zebrafish (Danio rerio)[J]. Aquatic Toxicology, 2016,177:316-323.
[18] Kretzschmar M, Giese R, Franke H, et al. Hepatic actions of levonorgestrel:correlations between biochemical and morphological findings[J]. Chemico-Biological Interactions, 1989,70(1/2):157-166.
[19] Khokha R, Walton P A, Possmayer F, et al. Effects of levonorgestrel on enzymes responsible for synthesis of triacylglycerols in rat liver[J]. Biochimica et Biophysica Acta, 1987,918(2):120-125.
[20] Khokha R, Wolfe B M. Hypotriglyceridemic effects of levonorgestrel in rats[J]. Atherosclerosis, 1984,52(3):329-338.
[21] Cardoso P G, Resende-de-Oliveira R, Rocha E, et al. Combined effects of increased temperature and levonorgestrel exposure on zebrafish female liver, using stereology and immunohistochemistry against catalase, CYP1A, HSP90and vitellogenin[J]. Environmental Pollution, 2019,252(Pt B):1059-1067.
[22] 王剑伟,曹文宣.中国本土鱼类模式生物稀有鮈鲫研究应用的历史与现状[J]. 生态毒理学报, 2017,12(2):20-33. Wang J, Cao W. Gobiocypris rarus as a Chinese native model organism:history and current situation[J]. Asian Journal of Ecotoxicology, 2017,12(2):20-33.
[23] Guan Y, Gao J, Zhang Y, et al. Effects of bisphenol A on lipid metabolism in rare minnow Gobiocypris rarus[J]. Comparative Biochemistry and Physiology Part C:Toxicology & Pharmacology, 2016,179:144-149.
[24] Yan S, Wang M, Liang X, et al. Environmentally relevant concentrations of carbamazepine induce liver histopathological changes and a gender-specific response in hepatic proteome of Chinese rare minnows (Gobiocypris rarus)[J]. Environmental Pollution, 2018,243:480-491.
[25] Zha J, Sun L, Zhou Y, et al. Assessment of 17α-ethinylestradiol effects and underlying mechanisms in a continuous, multigeneration exposure of the Chinese rare minnow (Gobiocypris rarus)[J]. Toxicology and Applied Pharmacology, 2008,226(3):298-308.
[26] Hua J, Han J, Guo Y, et al. Endocrine disruption in Chinese rare minnow (Gobiocypris rarus) after long-term exposure to low environmental concentrations of progestin megestrol acetate[J]. Ecotoxicology and Environmental Safety, 2018,163:289-297.
[27] Overturf M D, Overturf C L, Carty D R, et al. Levonorgestrel exposure to fathead minnows (Pimephales promelas) alters survival, growth, steroidogenic gene expression and hormone production[J]. Aquatic Toxicology, 2014,148:152-161.
[28] Tocher D R. Metabolism and functions of lipids and fatty acids in teleost fish[J]. Reviews in Fisheries Science, 2003,11:107-184.
[29] Field K, Dow C, Michael M. Part I:liver function in oncology:biochemistry and beyond[J]. The Lancet Oncology, 2008,9:1092-1101.
[30] Cheng J, Lv S, Nie S, et al. Chronic perfluorooctane sulfonate (PFOS) exposure induces hepatic steatosis in zebrafish[J]. Aquatic Toxicology, 2016,176:45-52.
[31] Qian L, Zhang J, Chen X, et al. Toxic effects of boscalid in adult zebrafish (Danio rerio) on carbohydrate and lipid metabolism[J]. Environmental Pollution, 2019,247:775-782.
[32] Baybutt R C, Rosales C, Brady H, et al. Dietary fish oil protects against lung and liver inflammation and fibrosis in monocrotaline treated rats[J]. Toxicology, 2002,175(1):1-13.
[33] Bouchard-Mercier A, Rudkowska I, Lemieux S, et al. Polymorphisms, de novo lipogenesis, and plasma triglyceride response following fish oil supplementation[J]. Journal of Lipid Research, 2013,54:2866-2873.
[34] Nagahama Y, Yoshikuni M, Yamashita M, et al. Molecular endocrinology of oocyte growth and maturation in fish[J]. Fish Physiology and Biochemistry, 1993,11(1-6):3-14.
[35] 李清亚,张松,祝扬,等.不同年龄及性别国人体脂和总体水分含量的测量分析[J]. 解放军预防医学杂志, 2007,25(6):412-415. Li Q Y, Zhang Y, Zhu Y, et al. Measurement and analysis of body fat and total body water in chinese with different age and sex[J]. Journal of Preventive Medicine of Chinese People's Liberation Army, 2007,25(6):412-415.
[36] 吴俊琳.鱼类脂肪组织核磁共振成像研究及斑马鱼(Danio rerio)脂代谢中的性别差异[D]. 上海:华东师范大学, 2015:35-53. Wu J L. Evaluation of the distribution of fatty tissues in fish using magnetic resonance imaging (MRI) and effects of gender on lipid metabolism in zebrafish, Danio rerio[J]. Shanghai:China Normal University, 2015:35-53.
[37] Alves-Bezerra M, Ramos I B, De Paula I F, et al. Deficiency of glycerol-3-phosphate acyltransferase 1decreases triacylglycerol storage and induces fatty acid oxidation in insect fat body[J]. Biochimica et Biophysica Acta, 2017,1862:324-336.
[38] Gimeno R E, Cao J. Thematic review series:glycerolipids. Mammalian glycerol-3-phosphate acyltransferases:new genes for an old activity[J]. Journal of Lipid Research, 2008,49:2079-2088.
[39] Raimondo S, Saieva L, Cristaldi M, et al. Label-free quantitative proteomic profiling of colon cancer cells identifies acetyl-CoA carboxylase alpha as antitumor target of Citrus limon-derived nanovesicles[J]. Journal of Proteomics, 2018,173:1-11.
[40] Hennigar R A, Pochet M, Hunt D A, et al. Characterization of fatty acid synthase in cell lines derived from experimental mammary tumors[J]. Biochimica et Biophysica Acta, 1998,1392:85-100.
[41] Semenkovich C F. Regulation of fatty acid synthase (FAS)[J]. Progress in Lipid Research, 1997,36:43-53.
[42] Zhang J, Sun P, Kong T, et al. Tributyltin promoted hepatic steatosis in zebrafish (Danio rerio) and the molecular pathogenesis involved[J]. Aquatic Toxicology, 2016,170:208-215.
[43] 李松林,廖凯,袁禹惠,等.DHA通过调控脂肪合成代谢影响大黄鱼肝脂沉积[OL]. 中国科技论文在线, 2016. Li S L, Liao K, Yuan Y H, et al. Regulation of DHA on hepatic lipid deposition through affecting lipogenesis in large yellow croaker[OL]. Chinese Scientific Paper Online, 2016.
[44] Eisenberg S. Metbolism of apolipoproteins and lipoproteins[J]. Curropinlipidol, 1990,1:205-215.
[45] Johnson W J, Mahlberg F H, Rothblat G H, et al. Cholesterol transport between cells and high-density lipoproteins[J]. Biochimica et Biophysica Acta-Molecular and Cell Biology of Lipids, 1991,1085:273-298.
[46] Longo N, Frigeni, M, Pasquali M. Carnitine transport and fatty acid oxidation[J]. Biochimica et Biophysica Acta, 2016,1863:2422-2435.
[47] Kerner J, Hoppel C. Fatty acid import into mitochondria[J]. Biochimica et Biophysica Acta-Molecular and Cell Biology of Lipids, 2000,1486:1-17.
湖北省自然科学基金资助项目（2018CFB324）；湖北省教育厅科学技术研究项目（Q20182010）；湖北中医药大学“青苗计划”项目（2017ZZX009）
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