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吡虫啉通过与雄性小鼠的雄激素受体相互作用来扰乱内分泌系统。

Imidacloprid disrupts the endocrine system by interacting with androgen receptor in male mice.

机构信息

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China.

Research Institute of Poyang Lake, Jiangxi Academy of Sciences, Nanchang 330029, China.

出版信息

Sci Total Environ. 2020 Mar 15;708:135163. doi: 10.1016/j.scitotenv.2019.135163. Epub 2019 Nov 20.

Abstract

In the current study, six-week-old male ICR mice were administered imidacloprid (IMI) at concentrations of 3, 10 and 30 mg/L for a duration of 10 weeks to investigate the toxicity of IMI on the endocrine system. We observed that testicular morphology was severely impaired and damaged, and the levels of serum testosterone (T) and the expression of androgen receptor (AR) decreased significantly. Molecular docking analysis suggested that IMI docks into the active site of AR successfully and that three key hydrogen bonds were formed with the active site residues Glu11, Gln41 and Lys138. The binding free energy value of the AR-IMI complex suggested a stable binding between IMI and AR. All these results indicated that IMI could interact with AR. In addition, major genes in the testis involved in the synthesis of cholesterol and T were generally inhibited, and the serum cholesterol sources were also reduced. Moreover, the aromatase in male mice was lacking after subchronic IMI exposure. The data acquired from the present study indicated that IMI could lead to endocrine disruption by interacting with AR and influence the expression of genes involved in the production of T in male mice.

摘要

在本研究中,将六周龄雄性 ICR 小鼠以 3、10 和 30mg/L 的浓度给予吡虫啉(IMI),持续 10 周,以研究 IMI 对内分泌系统的毒性。我们观察到睾丸形态严重受损,血清睾酮(T)水平和雄激素受体(AR)的表达显著降低。分子对接分析表明,IMI 成功对接入 AR 的活性位点,并与活性位点残基 Glu11、Gln41 和 Lys138 形成三个关键氢键。AR-IMI 复合物的结合自由能值表明 IMI 和 AR 之间存在稳定的结合。所有这些结果表明 IMI 可以与 AR 相互作用。此外,睾丸中参与胆固醇和 T 合成的主要基因通常受到抑制,血清胆固醇来源也减少。此外,雄性小鼠在亚慢性 IMI 暴露后缺乏芳香酶。本研究获得的数据表明,IMI 可以通过与 AR 相互作用导致内分泌失调,并影响雄性小鼠 T 产生相关基因的表达。

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