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pyrifos通过抑制永生GnRH神经元中的mTOR途径来诱导自

Gabriele Lori¹, Lucia Coppola¹, Marialuisa Casella²

¹Center for Gender-Specific Medicine, Istituto Superiore di Sanità, Rome, Italy.

|June 30, 2024

概括

pyrifos (CPF) 农药暴露抑制了mTOR信号传递,并诱导了小鼠GNRH神经元的自,即使在人类相关的低度下,也会影响下丘脑-垂体-腺 (HPG) 轴.

科学领域:

神经内分泌学神经内分泌学
毒理学毒理学毒理学
细胞生物学细胞生物学

背景情况:

pyrifos (CPF) 是一种广泛使用的农药,与神经发育和生殖问题有关.
造成CPF影响的机制,特别是在下丘脑,仍然不清楚.
脑下垂体 - 脑下垂体 - 卵巢 (HPG) 轴对于生殖功能至关重要,并且可以因环境因素而受到干扰.

研究的目的:

在人体相关度 (1 nM-100 nM) 下,研究 CPF 作用的分子机制在小鼠下丘脑的 GnRH 神经元 (GT1-7) 中.
评估CPF对神经元活力,增殖,亡和功能的影响.
阐明CPF对基因和蛋白质表达的影响,特别是与HPG轴相关的影响.

主要方法:

进行了细胞活力,增殖和亡测试.
使用了基因表达,传输电子显微镜 (TEM) 和蛋白质组学.
免疫光学和西部涂抹 (WB) 验证了关键发现.

主要成果:

在100nM时,CPF降低了细胞活力和GnRH分泌/基因表达.
CPF诱导了雌激素受体α/β,雄激素受体,芳酶和催产素受体的基因表达.
CPF抑制了mTOR信号传递,导致自和线粒体损伤,由TEM和WB证实.

结论:

CPF作为一个mTOR路径抑制剂,诱导GnRH神经元的自.
建议在CPF的作用中可能涉及雌激素受体α/雄激素受体信号传递.
在纳米度下,CPF对下丘脑的不良影响引发了对HPG轴中断的担忧.

关键词:

自自是一种自的过程.基基酸盐是一种基基酸盐.下丘脑的下丘脑是什么意思核受体是一种核受体.蛋白质组学是指蛋白质组学.在mTOROR中使用.

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