在初级精子细胞中,电离辐射诱导的Rela-Bclaf1-spliceosome调节轴的破坏,导致精子生成功能障碍
Hongjian Zhou1, Zhipeng Xu2, Chun Jiang1
1Institute of Laboratory Medicine, Jinling Hospital, First School of Clinical Medicine, Nanjing University School of Medicine, Southern Medical University, Zhongshan East Road 305, Nanjing, Jiangsu, 210002, China.
Cell communication and signaling : CCS
|January 31, 2025
概括
电离辐射 (IR) 通过Rela-Bclaf1-spliceosome通路破坏精子生成,从而损害男性的生育能力. NF-κB激动剂显示出作为放射性保护剂的潜力,以恢复精子功能.
科学领域:
- 生殖生物学 生殖生物学
- 分子生物学分子生物学
- 辐射生物学 辐射生物学
背景情况:
- 电离辐射 (IR) 通过引起丸损伤,严重威胁男性生育能力.
- 红外线诱导的精子生成障碍的确切机制尚未完全理解.
- 需要有效的辐射保护剂来缓解IR诱导的男性不孕症.
研究的目的:
- 为了阐明潜在的分子机制,IR诱导的精子生成障碍.
- 研究NF-κB激动剂作为辐射保护剂的治疗潜力.
主要方法:
- 在IR后的小鼠丸上进行批量和单细胞RNA测序 (scRNA-seq).
- 组织学分析,精子分析,西部涂抹和RT-qPCR.
- 在IR诱导的精子生成障碍模型中评估NF-κB激动剂.
主要成果:
- 6 Gy IR剂量诱导了精子生成障碍,影响了精子和初级精子细胞.
- 通过抑制Rela和Bclaf1.1,IR抑制了结合体通路,并损害了初级精子细胞分化.
- NF-κB激动剂通过上调Bclaf1和spliceosome基因来改善IR诱导的损伤,恢复正常的剪接和精子生成.
结论:
- 在初级精子细胞中确定了一种新的IR介导的Rela-Bclaf1-spliceosome调节轴.
- 瑞拉被提议作为一种潜在的药物标,用于减轻IR诱导的精子生成障碍.
- 研究结果提供了有关红外线损伤的见解,以及辐射保护剂的潜在治疗策略.
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