TERT转录和转移到线粒体中调节了小鼠精子细胞中[a]皮林/BPDE诱导的衰老和线粒体损伤
Haonan Cui1, Wang Yang1, Shijun He1
1Key Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
Toxicology and applied pharmacology
|August 14, 2023
概括
[a]烯 (BaP) 暴露会通过抑制端粒和线粒体功能来损害男性生殖细胞. 这项研究揭示了BaP.
科学领域:
- 环境毒理学环境毒理学
- 生殖生物学 生殖生物学
- 分子机制的分子机制
背景情况:
- 甲 (BaP) 是一种环境污染物,与男性生殖毒性有关.
- 精确的分子机制的BaP诱导的损伤的端粒和线粒体在精子细胞需要进一步的调查.
研究的目的:
- 探索 TERT 调节在 BaP 诱导的端粒和精子细胞中的线粒体损伤中的分子机制.
- 研究SIRT1/FOXO3a/c-MYC通路在BaP诱导的TERT抑制中的作用.
- 评估线粒体TERT表达对细胞功能的影响.
主要方法:
- 在实验室中,来自小鼠精子细胞的GC-2细胞暴露于[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE).
- 建立过度表达SIRT1,FOXO3a,c-MYC,野生型TERT和向线粒体的TERT的细胞模型.
- 在体内研究,涉及向ICR小鼠输入胃内BaP.
主要成果:
- 在GC-2细胞中,BPDE诱导了端粒功能障碍,S相停止和与衰老相关的分泌表型 (SASP),由端粒酶激动剂 (ABG) 缓解.
- 通过SIRT1/FOXO3a/c-MYC通路,BPDE抑制了TERT转录,导致端粒功能障碍和线粒体损伤,包括复合I损害.
- 针对线粒体的TERT过度表达比野生型TERT过度表达更有效地改善了线粒体功能;体内BaP暴露在小鼠中复制了这些发现.
结论:
- 通过抑制TERT转录和线粒体TERT表达来诱导精子细胞中的端粒和线粒体损伤,BAP暴露会导致男性生殖功能障碍.
- 这项研究阐明了BaP男性生殖毒性的分子机制,突出了TERT调节作为一个关键因素.
- 这些发现为开发针对BAP诱导的男性生殖损害的干预措施提供了新的视角.
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