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微囊素-LR通过改变Sertoli细胞中的m6A修饰来诱导乳酸生产中断
Xiannan Meng1, Wenju Li2, Qingxuan Wu1
1Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu 221004, China.
Ecotoxicology and environmental safety
|July 23, 2023
概括
微囊素-LR (MC-LR) 暴露会通过降低乳酸脱酶A (Ldha) 表达来损害男性生育能力. 这种由甲基转移酶3 (Mettl3) 介导的表观遗传变化会导致精子损伤和生殖细胞亡.
科学领域:
- 环境毒理学环境毒理学
- 生殖生物学 生殖生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 微囊素-LR (MC-LR) 是一种已知会损害男性生殖功能的毒素.
- 之前的研究表明,在暴露于MC-LR后,小鼠丸的功能变化.
研究的目的:
- 调查 MC-LR 诱导的男性不孕症背后的分子机制.
- 探索乳酸脱酶A (Ldha) 的作用及其对MC-LR毒性的调节.
主要方法:
- 小鼠通过口服暴露在不同剂量的MC-LR中,持续180天.
- 高通量测序用于分析丸中的基因表达变化.
- 研究了甲基转移酶3 (Mettl3) 在调节Ldha mRNA甲基化 (m6A) 中的作用.
主要成果:
- 暴露于MC-LR导致生殖细胞亡的增加和精子质量的降低.
- 乳酸脱酶A (Ldha) 表达在暴露于MC-LR的丸中显著下降.
- 在塞尔托利细胞中,MC-LR降低了Mettl3的调节,减少了Ldha mRNA的甲基化和稳定性.
结论:
- MC-LR以M6A-依赖的方式抑制Ldha表达,导致男性不育.
- 这种涉及Mettl3和Ldha的表观遗传机制会影响精子细胞亡和精子质量.
- 这些发现为MC-LR诱导的男性生殖毒性提供了新的视角.
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