хлорпирифос通过塞尔托利细胞中的铁死诱导精子生成功能障碍
Yan Fu1,2, Xu Huang1,2, Siyuan Wang1,2
1Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
Genes & diseases
|July 11, 2025
概括
通过诱导塞尔托利细胞中的铁亡,通过增强的钟食症和减少HIF-1α信号传递,暴露于杀剂化物破坏了老鼠丸,损害了血液丸屏障和精子生成.
科学领域:
- 环境毒理学环境毒理学
- 生殖生物学 生殖生物学
- 细胞毒理学 细胞毒理学
背景情况:
- pyrifos (CPF) 是一种被广泛使用的有机酸盐农药,已知具有神经毒性.
- 新出现的证据表明,CPF可能会对男性生殖健康产生负面影响,特别是精子生成.
- 导致CPF引起的生殖毒性背后的精确分子机制在很大程度上是未知的.
研究的目的:
- 研究CPF诱导异常精子生成的分子机制.
- 确定铁和钟在CPF诱导的丸功能障碍中的作用.
- 阐明CPF对血液丸屏障 (BTB) 完整性的影响.
主要方法:
- 雄性斯普拉格-道利大鼠在30天内暴露在不同度的CPF中.
- 在Sertoli细胞上进行RNA测序,以确定差异表达的基因.
- 在丸组织和塞尔托利细胞中评估了铁亡标记物,氧化应激指标和钟活动.
- 用费罗斯塔丁-1 (ferroptosis抑制剂) 和Arntl敲击来评估功能影响.
主要成果:
- 暴露在CPF中破坏了血液丸屏障 (BTB) 和受损的精子生成.
- RNA测序揭示了塞尔托利细胞中铁灭相关基因的显著改变.
- 暴露于CPF引发了铁亡,由增加的甲和Fe2+水平以及降低的谷氨水平证明.
- 费罗斯塔丁-1治疗恢复了塞尔托利细胞的结节功能,而Arntl敲击破坏了它.
- 钟活动增强,伴随着RNATL和HIF-1α表达的减少.
结论:
- CPF诱导丸塞尔托利细胞中的铁亡,导致BTB破坏和精子生成功能障碍.
- 增强的钟和随后的HIF-1α下调是CPF毒性的关键机制.
- 这些发现凸显了铁亡作为农药诱导的男性生殖毒性的关键途径.
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