核受体介导的阿特拉津致鹌鹑睾丸毒性效应研究
发布时间:2019-06-05 00:36
【摘要】:阿特拉津(Atrazine,ATR)是目前世界范围内应用量最大的三氯苯类除草剂,主要通过农业径流和灌溉用水等途径进入生态环境系统,由于其在生物体内的蓄积及通过食物链的传递从而对各物种机体都有损伤作用。近些年,由于ATR使用量大以及在环境中存留期长,对生物体表现出较为显著的雌激素样作用,其毒理学研究广受关注,然而ATR对禽类生殖毒性研究较少。本试验以雄性鹌鹑为受试动物,以灌胃方式进行ATR染毒,观察鹌鹑的整体状态及睾丸的病理学,检测了睾丸抗氧化功能、CYP450酶系、激素水平、下丘脑-垂体-睾丸轴类固醇激素相关因子及相关核受体表达。结果表明:1.ATR暴露引发鹌鹑睾丸组织病理组织学和超微结构改变,诱发睾丸发育障碍,并抑制鹌鹑生长。2.ATR暴露能够诱导鹌鹑睾丸组织中自由基含量增加,脂质过氧化物生成过量,抑制抗氧化酶系统活性,进而诱发氧化应激,发挥损伤鹌鹑睾丸组织的作用。3.ATR暴露能够激活芳香烃受体(AHR)、孕烷X受体(PXR)与组成型雄甾烷受体(CAR)等核受体的表达,调控睾丸组织中CYPs亚型mRNA的表达水平,增加CYP450含量,影响CYP450酶系相关酶活性,发挥致鹌鹑雄性生殖毒性作用。4.ATR暴露能够影响孕激素受体(PGR)和雌激素受体(ERα与ERβ)等核受体的表达,干扰下丘脑-垂体-睾丸轴类固醇激素相关因子的表达,降低CYP11A1和CYP17A1蛋白水平,干扰雄性鹌鹑性腺轴的正常调节功能,阻碍睾酮的合成通路,这是其致鹌鹑雄性生殖毒性的重要机制之一。得出结论,ATR暴露能够引起鹌鹑睾丸组织损伤,通过核受体介导可以调控CYP450酶系活性及CYPs亚型的基因表达,干扰性腺轴的调控功能,使性激素分泌紊乱,阻碍睾酮的合成对鹌鹑生殖系统产生严重的毒性作用。
[Abstract]:Atrazin (Atrazine,ATR) is the most widely used trichlorobenzene herbicide in the world, which mainly enters the ecological environment system through agricultural runoff and irrigation water. Because of its accumulation in organisms and its transmission through the food chain, it can damage the body of all species. In recent years, due to the large use of ATR and the long retention period in the environment, it has shown significant estrogen-like effect on organisms, so its toxicological research has attracted much attention, but the study of reproductive toxicity of ATR to poultry is less. In this experiment, male quail was exposed to ATR by intragastric administration. The overall state of quail and the pathology of testes were observed. The antioxidant function, CYP450 enzyme system and hormone level of testes were measured. Expression of steroid hormone related factors and related nuclear receptors in Hypothalamic-pituitary-testicular axis. The results showed that 1.ATR exposure induced pathological and ultrastructure changes in testicular tissue of quail, induced testicular development disorder and inhibited the growth of quail. 2. ATR exposure could induce the increase of free radical content in testicular tissue of quail. Excessive production of lipid peroxide, inhibition of antioxidant enzyme system activity, and then induce oxidative stress, play the role of injury to quail testicular tissue. 3. ATR exposure can activate aromatic hydrocarbon receptor (AHR), The expression of nuclear receptors such as progesterone X receptor (PXR) and constituent androsterane receptor (CAR) regulated the expression of CYPs subtypes mRNA in testicular tissue, increased the content of CYP450, and affected the activity of CYP450 enzyme related enzymes. 4. ATR exposure can affect the expression of progesterone receptor (PGR) and estrogen receptor (ER 伪 and ER 尾), and interfere with the expression of steroid hormone related factors in Hypothalamic pituitary testicular axis. It is one of the important mechanisms of male reproductive toxicity in quails to reduce the levels of CYP11A1 and CYP17A1 proteins, interfere with the normal regulation of sexual gland axis of male quails, and hinder the synthetic pathway of testosterone. It is concluded that ATR exposure can cause testicular tissue damage in quail, regulate the activity of CYP450 enzyme system and the gene expression of CYPs subtypes through nuclear receptor, interfere with the regulation function of gonadal axis, and disorder the secretion of sex hormones. Hindering the synthesis of testosterone has a serious toxic effect on the reproductive system of quail.
【学位授予单位】:东北农业大学
【学位级别】:硕士
【学位授予年份】:2016
【分类号】:S858.39
,
本文编号:2493117
[Abstract]:Atrazin (Atrazine,ATR) is the most widely used trichlorobenzene herbicide in the world, which mainly enters the ecological environment system through agricultural runoff and irrigation water. Because of its accumulation in organisms and its transmission through the food chain, it can damage the body of all species. In recent years, due to the large use of ATR and the long retention period in the environment, it has shown significant estrogen-like effect on organisms, so its toxicological research has attracted much attention, but the study of reproductive toxicity of ATR to poultry is less. In this experiment, male quail was exposed to ATR by intragastric administration. The overall state of quail and the pathology of testes were observed. The antioxidant function, CYP450 enzyme system and hormone level of testes were measured. Expression of steroid hormone related factors and related nuclear receptors in Hypothalamic-pituitary-testicular axis. The results showed that 1.ATR exposure induced pathological and ultrastructure changes in testicular tissue of quail, induced testicular development disorder and inhibited the growth of quail. 2. ATR exposure could induce the increase of free radical content in testicular tissue of quail. Excessive production of lipid peroxide, inhibition of antioxidant enzyme system activity, and then induce oxidative stress, play the role of injury to quail testicular tissue. 3. ATR exposure can activate aromatic hydrocarbon receptor (AHR), The expression of nuclear receptors such as progesterone X receptor (PXR) and constituent androsterane receptor (CAR) regulated the expression of CYPs subtypes mRNA in testicular tissue, increased the content of CYP450, and affected the activity of CYP450 enzyme related enzymes. 4. ATR exposure can affect the expression of progesterone receptor (PGR) and estrogen receptor (ER 伪 and ER 尾), and interfere with the expression of steroid hormone related factors in Hypothalamic pituitary testicular axis. It is one of the important mechanisms of male reproductive toxicity in quails to reduce the levels of CYP11A1 and CYP17A1 proteins, interfere with the normal regulation of sexual gland axis of male quails, and hinder the synthetic pathway of testosterone. It is concluded that ATR exposure can cause testicular tissue damage in quail, regulate the activity of CYP450 enzyme system and the gene expression of CYPs subtypes through nuclear receptor, interfere with the regulation function of gonadal axis, and disorder the secretion of sex hormones. Hindering the synthesis of testosterone has a serious toxic effect on the reproductive system of quail.
【学位授予单位】:东北农业大学
【学位级别】:硕士
【学位授予年份】:2016
【分类号】:S858.39
,
本文编号:2493117
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