霉菌毒素单独或联合暴露对睾丸间质细胞毒性作用研究进展
Research Progress on Toxic Effect of Individual or Combined Mycotoxins Exposure to Leydig Cells
-
摘要: 霉菌毒素是由霉菌产生的一系列有毒次级代谢产物，广泛存在于被污染的饲料或饲料原料中。这些代谢物在饲料储藏、运输或加工过程中均可产生，具有分布广、毒性强等特点，是食品和饲料中最主要的污染物，可对雄性生殖系统产生危害。霉菌毒素可导致睾酮合成和分泌能力下降、精子生成缺陷和质量下降，甚至造成不育等。睾丸间质细胞主要负责雄性激素的合成和分泌，对维持雄性机体生殖机能具有重要意义。然而这类细胞对玉米赤霉烯酮、T-2毒素等霉菌毒素比较敏感。研究表明，自然条件下多种毒素共同污染非常普遍，且多种毒素对动物健康和生殖系统的联合毒性比单一毒素的危害更严重。霉菌毒素已被证实可诱导的睾丸细胞DNA损伤、线粒体损伤以及细胞凋亡或自噬等。鉴于此，笔者综述了霉菌毒素对睾丸间质细胞毒性作用的研究进展，旨在为开展单一或多种霉菌毒素暴露对睾丸间质细胞的毒性作用机制研究提供思路和理论支持。Abstract: Mycotoxins are a group of secondary toxic metabolites produced by a variety of fungi, which could be detected in feedstuffs and feed ingredients at any stage of storage, transport, or processing. Due to high toxicity and widespread distribution, mycotoxins are considered among the most critical contaminants in foods and feeds, which generally results in a significant damage to male reproductive system in animals. The common clinical symptoms and signs are reduction of testosterone synthesis and secretion, defect in sperm production and low quality, and possibly even infertility. Leydig cells (LCs) responsible for the biosynthesis and secretion of androgens, which are critical for the development of the reproductive function in the male. As one of the major testicular cells, LCs are sensitive to certain mycotoxins, such as zearalenone and T-2 toxin. Co-contamination by multiple mycotoxins occurs naturally, and exerts greater negative impacts on health and productivity of animals than contamination by individual mycotoxin. Mycotoxin-induced DNA and mitochondrial damages, even cellular apoptosis or autophagy have been reported. In lights of above-mentioned, this study is aimed to provide theoretical supports for exploring the toxic mechanism of individual or multiple mycotoxins exposure to LCs by summarizing the recent developments of toxic effects of mycotoxins on LCs.
-
Key words:
- mycotoxins /
- zearalenone /
- T-2 toxin /
- Leydig cells /
- mechanism of toxicity
-
-
Ahmad A, Jae-Hyuk Y. Occurrence, toxicity, and analysis of major mycotoxins in food[J]. International Journal of Environmental Research and Public Health, 2017, 14(6):632-652 刘水灵, 车丽涛, 张春勇, 等. 饲料中霉菌毒素的研究进展[J]. 安徽农业科学, 2018, 46(31):4-7 Liu S L, Che L T, Zhang C Y, et al. Research progress of mycotoxin in feed[J]. Journal of Anhui Agricultural Science, 2018, 46(31):4-7(in Chinese)
Huang X L, Han J Z, Qu D F. Research advances in detection techniques of mycotoxin residues in animal tissues[J]. Food Science, 2013, 34(5):293-296 Rader J, D'Ovidio K, Oles C, et al. Determination of aflatoxins and ochratoxin A in ginseng and other botanical roots by immunoaffinity column cleanup and liquid chromatography with fluorescence detection[J]. Journal of AOAC International, 2006, 89(3):624-630 欧阳斌, 耿强. 针刺治疗男性不育症的疗效及作用机制述评[J]. 中国中西医结合杂志, 2018, 38(5):520-522 Ouyang B, Geng Q. Commentary on efficacy and mechanism of acupuncture for male infertility[J]. Chinese Journal of Integrative Medicine, 2018, 38(5):520-522(in Chinese)
Uriah N, Ibeh I N, Oluwafemi F. A study on the impact of aflatoxin on human reproduction[J]. African Journal of Reproductive Health, 2001, 5(1):106-110 刘建中, 郭海彬, 邓春华, 等. 大鼠睾丸Leydig细胞的培养和鉴定[J]. 中华男科学杂志, 2006, 12(1):14-17 Liu J Z, Guo H B, Deng C H, et al. The culture and identification of rat testis Leydig cell[J]. National Journal of Andrology, 2006, 12(1):14-17(in Chinese)
Bjerregaard P, Bro-Rasmussen F, Reumert T. Ultrastructural development of fetal rabbit testis[J]. Zeitschrift Für Zellforschung Und Mikroskopische Anatomie, 1974, 147(3):401-413 Park S Y, Minghan T, Larry J J. Distinct roles for steroidogenic factor 1 and desert hedgehog pathways in fetal and adult Leydig cell development[J]. Endocrinology, 2007, 148(8):3704-3710 郭隽, 张立实, 彭双清. 镰刀菌毒素生殖发育毒性研究进展[J]. 中国食品卫生杂志, 2013, 25(5):474-478 Guo J, Zhang L S, Peng S Q. Review of reproductive and developmental toxicity studies of fusarium toxins[J]. Chinese Journal of Food Hygiene, 2013, 25(5):474-478(in Chinese)
甄建伟. 玉米赤霉烯酮对睾丸间质细胞的毒性作用[D]. 扬州:扬州大学, 2012:1-62 Zhen J W. Toxicity of zearalenone to Leydig cells[D]. Yangzhou:Yangzhou University, 2012:1 -62(in Chinese)
郑王龙, 刘青, 王亚军, 等. 玉米赤霉烯酮对小鼠睾丸间质细胞线粒体的损伤作用[J]. 中国兽医学报, 2014, 34(7):1157-1161 Zheng W L, Liu Q, Wang Y J, et al. Toxicity of zearalenone on the mitochondria of mice Leydig cells[J]. Chinese Journal of Veterinary Science, 2014, 34(7):1157-1161(in Chinese)
王亚军. 玉米赤霉烯酮诱导大鼠Leydig细胞凋亡及自噬保护作用[D]. 扬州:扬州大学, 2014:1-51 Wang Y J. Zearalenone induces apoptosis and cytoprotective autophagy in primary Leydig cells[D]. Yangzhou:Yangzhou University, 2014:1 -51(in Chinese)
杨建英, 张勇法, 白雪飞, 等. T-2毒素对小鼠睾丸间质细胞活力和功能的影响[J]. 内蒙古农业大学学报:自然科学版, 2014, 35(4):10-13 Yang J Y, Zhang Y F, Bai X F, et al. Toxicity studies of T-2 toxin on primary cultured mouse Leydig cells[J]. Journal of Inner Mongolia Agricultural University:Natural Science Edition, 2014, 35(4):10-13(in Chinese)
Yang J Y, Zhang Y F, Meng X P, et al. T-2 toxin inhibits gene expression and activity of key steroidogenesis enzymes in mouse Leydig cells[J]. Toxicology in Vitro, 2015, 29(5):1166-1171 李顺意, 于秋香, 向腊, 等. 真菌毒素玉米赤霉烯酮生物降解的研究进展[J]. 生物工程学报, 2018, 34(4):489-500 Li S Y, Yu Q X, Xiang L, et al. Progress in bio-degradation of mycotoxin zearalenone[J]. Chinese Journal of Biotechnology, 2018, 34(4):489-500(in Chinese)
D'Mello J P F, Placinta C M, Macdonald A M C. Fusarium mycotoxins:A review of global implications for animal health, welfare and productivity[J]. Animal Feed Science and Technology, 1999, 80(3-4):183-205 李雨哲. 玉米赤霉烯酮对生殖靶器官细胞毒性机制研究[D]. 北京:中国农业大学, 2014:1-86 Li Y Z. Investigation of the mechanism of the reproductive toxicity of zearalenone on cells from target organ[D]. Beijing:China Agricultural University, 2014:1 -86(in Chinese)
Barth S, Glick D, Macleod K F. Autophagy:Assays and artifacts[J]. Journal of Pathology, 2010, 221(2):117-124 Yang D, Jiang T, Lin P, et al. Apoptosis inducing factor gene depletion inhibits zearalenone-induced cell death in a goat Leydig cell line[J]. Reproductive Toxicology, 2017, 67:129-139 Wang Y, Zheng W, Bian X, et al. Zearalenone induces apoptosis and cytoprotective autophagy in primary Leydig cells[J]. Toxicology Letters, 2014, 226(2):182-191 张焕, 王加启, 高亚男, 等. 霉菌毒素对多种细胞DNA损伤的研究进展[J]. 动物营养学报, 2017, 29(2):403-409 Zhang H, Wang J Q, Gao Y N, et al. Research progress of mycotoxins on DNA damage of different cells[J]. Chinese Journal of Animal Nutrition, 2017, 29(2):403-409(in Chinese)
黄沁怡. 玉米赤霉烯酮诱发睾丸间质肿瘤机制的体外研究[D]. 扬州:扬州大学, 2015:22-29 Huang Q Y. Study on the mechanism of zearalenone-induce testicular stromal tumor in vitro[D]. Yangzhou:Yangzhou University, 2015:22 -29(in Chinese)
马明慧, 马悦佼, 孙婕, 等. 线粒体代谢与干细胞的命运决定[J]. 中华细胞与干细胞杂志(电子版), 2018, 8(3):54-59 Ma M H, Ma Y J, Sun J, et al. Mitochondrial metabolism and stem cells fate[J]. Chinese Journal of Cell and Stem Cell (Electronic Edition), 2018, 8(3):54-59(in Chinese) Li Y, Zhang B, Huang K, et al. Mitochondrial proteomic analysis reveals the molecular mechanisms underlying reproductive toxicity of zearalenone in MLTC-1 cells[J]. Toxicology, 2014, 324(10):55-67 杨望, 邹鹏, 曹佳, 等. BPDE损伤线粒体抑制小鼠睾丸间质细胞睾酮生成[J]. 第三军医大学学报, 2019, 41(6):529-535 Yang W, Zou P, Cao J, et al. Role of mitochondrial damage in BPDE-induced inhibition of testosterone production in mouse Leydig cells[J]. Journal of Third Military Medical University, 2019, 41(6):529-535(in Chinese)
Shabalina I G, Landreh L, Edgar D, et al. Leydig cell steroidogenesis unexpectedly escapes mitochondrial dysfunction in prematurely aging mice[J]. The FASEB Journal:Official Publication of the Federation of American Societies for Experimental Biology, 2015, 29(8):3274-3286 Liu Q, Wang Y J, Gu J H, et al. Zearalenone inhibits testosterone biosynthesis in mouse Leydig cells via the crosstalk of estrogen receptor signaling and orphan nuclear receptor Nur77 expression[J]. Toxicology in Vitro, 2014, 28(4):647-656 董双, 何剑斌, 张燚, 等. 玉米赤霉烯酮对雄性小鼠生殖系统的毒性作用[J]. 畜牧与兽医, 2016, 48(6):25-29 Dong S, He J B, Zhang Y, et al. Toxic effects of zearalenone on male reproductive system in mice[J]. Animal Husbandry and Veterinary Medicine, 2016, 48(6):25-29(in Chinese)
Zhou S Y, Wang Y Y, Ma L K, et al. Zearalenone delays rat Leydig cell regeneration[J]. Toxicological Sciences, 2018, 164(1):60-71 向雨珂, 熊犍, 张晓琳, 等. T-2毒素脱毒菌株的筛选及脱毒机制初探[J]. 食品科技, 2017, 42(11):27-33 Xiang Y K, Xiong J, Zhang X L, et al. Screening of T-2 toxin detoxification strains and the mechanism of detoxification[J]. Food Science and Technology, 2017, 42(11):27-33(in Chinese)
李丽霞, 尚书凤. T-2毒素的毒性及其作用机制与代谢研究进展[J]. 湖北农业科学, 2015, 54(21):5207-5210 Li L X, Shang S F. Advances in toxicity, mechanism of action and metabolism of T-2 toxin[J]. Hubei Agricultural Science, 2015, 54(21):5207-5210(in Chinese)
Wu J, Huang W M, Xiao H S, et al. Procyanidins B2 reverses the T-2 toxin-induced mitochondrial apoptosis in TM3 Leydig cells[J]. Journal of Functional Foods, 2018, 45:118-128 Zhang Y F, Yang J Y, Li Y K, et al. Toxicity and oxidative stress induced by T-2 toxin in cultured mouse Leydig cells[J]. Toxicology Mechanisms and Methods, 2017, 27(2):100-106 Łuczaj W, Skrzydlewska E. DNA damage caused by lipid peroxidation products[J]. Cellular and Molecular Biology Letters, 2003, 8(2):391-413 Yuan Z H, Matias F B, Yi J E, et al. T-2 toxin-induced cytotoxicity and damage on TM3 Leydig cells[J]. Comparative Biochemistry and Physiology Part C:Toxicology & Pharmacology, 2016, 181-182:47-54 韩顺顺, 陈玉琪, 何浩荣, 等. T-2毒素通过PI3K/AKT/mTOR信号通路诱导鸡肝细胞自噬和凋亡[C]//第八届中国畜牧科技论坛论文集. 重庆:中国畜牧兽医学会信息学分会和重庆市畜牧科学院, 2018 周煜, 田亚南, 邬静. T-2毒素在L02细胞中诱导凋亡与自噬的研究[C]//中国毒理学会兽医毒理学委员会与中国畜牧兽医学会兽医食品卫生学分会联合学术研讨会暨中国毒理学会兽医毒理学委员会第5次全国会员代表大会会议论文集. 北京:中国毒理学会兽医毒理学委员会与中国畜牧兽医学会兽医食品卫生学分会, 2017 Yang J Y, Zhang Y F, Meng X P, et al. Delayed effects of autophagy on T-2 toxin-induced apoptosis in mouse primary Leydig cells[J]. Toxicology and Industrial Health, 2019, 35(3):256-263 张焕, 王加启, 高亚男, 等. 霉菌毒素对畜禽的危害及其毒性降解研究进展[J]. 中国饲料, 2017(4):12-16 Zhang H, Wang J Q, Gao Y N, et al. Research progress of the mycotoxins harm to livestock and its degradation toxicity[J]. China Feed, 2017 (4):12-16(in Chinese)
Krisztina B, Ildikó B, Tamás P, et al. Evaluation of spermatological parameters in ochratoxin A-challenged boars[J]. Theriogenology, 2003, 60(2):199-207 Dufau L M. Endocrine regulation and communicating functions of the Leydig cell[J]. Annual Review of Physiology, 1988, 50(1):483-508 Kalayou S, Ndossi D, Frizzell C, et al. An investigation of the endocrine disrupting potential of enniatin B using in vitro bioassays[J]. Toxicology Letters, 2015, 233(2):84-94 Eze U A, Huntriss J, Routledge M N, et al. Toxicological effects of regulated mycotoxins and persistent organochloride pesticides:in vitro cytotoxic assessment of single and defined mixtures on MA-10 murine Leydig cell line[J]. Toxicology in Vitro, 2018, 48:93-103 Savard C, Nogues P, Boyer A, et al. Prevention of deoxynivalenol- and zearalenone-associated oxidative stress does not restore MA-10 Leydig cell functions[J]. Toxicology, 2016, 341-343:17-27 -
点击查看大图
计量
- 文章访问数: 2149
- HTML全文浏览数: 2149
- PDF下载数: 49
- 施引文献: 0
下载:
