与GenX相关的分子特征与丸衰老和男性不孕症重叠:一个多omics整合分析
Zhuozhi Gong1, Qiujian Feng2, Siyuan Tang3
1Department of Andrology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China.
概括
通过影响精子老化和细胞间通信,GenX暴露会导致丸毒性. 像SOD1和FOXO3这样的关键基因可能作为GenX生殖毒性的生物标志物.
科学领域:
- 环境毒理学环境毒理学
- 生殖生物学 生殖生物学
- 基因组学就是基因组学.
背景情况:
- 基因X (HFPO-DA) 是一种和多基基物质 (PFAS) 替代品,与丸毒性有关.
- 了解GenX对丸衰老和男性不孕症的影响至关重要.
研究的目的:
- 研究细胞类型特定的衰老敏感性和衰老人类丸的细胞间通信.
- 确定关键的基因和途径参与GenX诱导的丸毒性和男性不孕.
- 为了验证GenX生殖毒性的潜在生物标志物.
主要方法:
- 综合单细胞RNA测序 (scRNA-seq) 数据来自人类丸衰老和男性不孕不育数据集.
- 使用LASSO回归和SVM-RFE来识别枢纽基因.
- 在使用RT-qPCR的GenX暴露的老鼠丸组织中验证了枢纽基因表达.
- 进行了分子对接,以评估GenX蛋白相互作用.
主要成果:
- 精子体表现出最高的衰老灵敏度与细胞间通信下降.
- 四个枢纽基因 (SOD1,XRCC5,FOXO3,POLB) 被确定为男性不孕症的潜在诊断标记物.
- 在暴露于GenX的老鼠中,RT-qPCR证实了SOD1,XRCC5,FOXO3 (上调) 和POLB (下调) 的差异表达.
- 功能丰富分析突出了FoxO信号传递,细胞衰老和DNA修复途径.
结论:
- SOD1,XRCC5,FOXO3和POLB是GenX诱导的生殖毒性的候选生物标志物.
- 氧化应激和基因组维护是GenX丸毒性的关键机制.
- 暴露于GenX会破坏丸衰老和细胞间通信,导致男性不孕.
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