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通过激活cGAS-STING通路并降低小鼠卵细胞质量,托利德暴露会触发卵巢炎症

Si-Yao Cheng¹, Yi-Fan Yang¹, Ya-Long Wang²

¹Medical College, Guangxi University, Nanning, Guangxi, 530004, China.

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association

|December 13, 2024

概括

ptolide (TPL) 通过影响线粒体功能和激活炎症通路而导致卵巢损伤. 这导致生育能力和卵细胞质量下降,阻碍卵泡发育.

科学领域:

毒理学毒理学毒理学
生殖生物学生殖生物学
分子生物学分子生物学

背景情况:

来自Tripterygium wilfordii的Triptolide (TPL) 具有抗瘤和抗免疫用途.
TPL导致多器官毒性,包括女性生殖系统损伤.
由于TPL引起的卵巢损伤的机制尚不清楚.

研究的目的:

研究TPL诱导的卵巢毒性的机制.
评估TPL对卵巢功能和卵细胞质量的影响.
确定涉及TPL生殖副作用的分子途径.

主要方法:

对于TPL暴露的小鼠毒理模型.
评估卵巢系数和生育能力.
对线粒体功能,mtDNA释放和cGAS-STING通路激活的分析.
评估卵细胞中介性成熟,螺旋和MTOC形态.
减少表示双硫酸盐序列 (RRBS) 进行确认.

主要成果:

在小鼠中,TPL暴露降低了卵巢系数和生育能力.
TPL破坏了线粒体功能,导致mtDNA释放和cGAS-STING通路激活.
观察到卵巢炎症和卵泡发育障碍.
TPL 损害了卵细胞中介成熟,影响了螺旋和MTOCs.

结论:

TPL通过线粒体功能障碍和炎症途径诱导卵巢损伤.
毛囊发育受损和卵细胞质量下降是TPL暴露的关键后果.
了解这些机制对于管理TPL的生殖毒性至关重要.

关键词:

在表观遗传学上,表观遗传学是表观遗传学.卵巢卵巢卵巢三托利德是一种三托利德.在cGAS-STING路径中.释放mtDNA的时间

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