| 王华沛,段能亮,高志翔,等.电离辐射暴露后睾丸的单细胞转录组分析及生殖毒性机制初步探讨[J].中华放射医学与防护杂志,2026,46(1):29-35.Wang Huapei,Duan Nengliang,Gao Zhixiang,et al.Single-cell transcriptome analysis of testes following ionizing radiation exposure and preliminary exploration of reproductive toxicity mechanisms[J].Chin J Radiol Med Prot,2026,46(1):29-35 |
| 电离辐射暴露后睾丸的单细胞转录组分析及生殖毒性机制初步探讨 |
| Single-cell transcriptome analysis of testes following ionizing radiation exposure and preliminary exploration of reproductive toxicity mechanisms |
| 投稿时间：2024-12-30 |
| DOI：10.3760/cma.j.cn112271-20241230-00500 |
| 中文关键词: 电离辐射 睾丸损伤 单细胞测序 间质细胞 |
| 英文关键词:Ionizing radiation Testicular injury Single-cell sequencing Leydig cell |
| 基金项目:江苏省职业健康科研项目(JSZJ20233201);苏州市科技局重点临床技术(SKY2023004);苏州市社会发展项目(2023SS19) |
| 作者 | 单位 | E-mail | | 王华沛 | 苏州大学附属第二医院泌尿外科, 苏州 215000 | | | 段能亮 | 苏州大学附属第二医院泌尿外科, 苏州 215000 | | | 高志翔 | 苏州大学附属第二医院泌尿外科, 苏州 215000 | | | 冉元帅 | 苏州大学附属第二医院泌尿外科, 苏州 215000 | | | 孙龙 | 苏州大学附属第二医院泌尿外科, 苏州 215000 | | | 龚世炜 | 苏州大学附属第二医院泌尿外科, 苏州 215000 | | | 崔凤梅 | 苏州大学放射医学与防护学院, 苏州 215000 | | | 陈秋 | 苏州大学放射医学与防护学院, 苏州 215000 | liuxiaolong2005@suda.edu.cn | | 薛波新 | 苏州大学附属第二医院泌尿外科, 苏州 215000 | | | 刘晓龙 | 苏州大学附属第二医院泌尿外科, 苏州 215000 | |
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| 中文摘要: |
| 目的 从单细胞层面分析电离辐射对人睾丸细胞基因表达的影响及相关机制。方法 获取意外暴露于192Ir源9个月后的男性睾丸组织单细胞RNA测序数据,应用Seurat包进行细胞分群注释,计算辐射损伤组织和正常组织中各群细胞的基因表达变化,获取差异基因并进行功能富集分析,使用Monocle包分析间质细胞发育轨迹,使用CellChat包评估全部睾丸细胞间的通信通路变化。结果 电离辐射暴露导致睾丸生殖细胞显著减少,如未分化精原细胞和精母细胞的比例从正常组的78%骤降至1.1%。统计共筛选出7 758个差异表达基因(log2FC≥0.25,P<0.05),其中主要富集于精子发生(P=1.2×10-10)、PI3K-AKT-mTOR(P=3.1×10-8)信号通路、Notch(P=6.7×10-5)信号通路等,提示生殖功能相关通路明显受影响。电离辐射暴露后间质细胞比例由34.62%增至43.16%,内皮细胞比例由28.73%降至18.64%,且间质细胞中磷脂酶Cγ2(PLCG2)、胰岛素样生长因子1(IGF1)等增殖相关基因上调,提示细胞成分和功能的重构。支持细胞在总细胞中的比例下降,但在体细胞群中占比上升。结论 从单细胞层面证实了电离辐射通过削弱生殖细胞和重塑体细胞格局,显著干扰男性生殖系统功能,为深入理解和干预辐射所致生殖毒性提供了分子依据。 |
| 英文摘要: |
| Objective To investigate how ionizing radiation affects gene expression and toxicity mechanisms in human testicular cells at the single-cell level. Methods Single-cell RNA sequencing was performed on testicular tissue from a male patient nine months after accidental 192Ir exposure. Data analysis included cell clustering and annotation (Seurat), identification of differentially expressed genes (DEGs) and their functional enrichment, developmental analysis of Leydig cells (Monocle), and assessment of cell-cell communication (CellChat). Results Ionizing radiation induced a sharp reduction in germ cells, with undifferentiated spermatogonia and spermatocytes dropping from 78% in controls to 1.1%. A total of 7 758 DEGs (log2FC≥0.25, P<0.05) were predominatly enriched in pathways associated with spermatogenesis (P = 1.2×10-10), PI3K-AKT-mTOR (P = 3.1×10-8), and Notch (P = 6.7×10-5), indicating significant disruption of reproductive functions. The proportion of Leydig cells increased from 34.62% to 43.16%, whereas endothelial cells decreased from 28.73% to 18.64%. Proliferation-related genes, such as phospholipase C gamma 2(PLCG2) and insulin like growth factor 1(IGF1) were upregulated in Leydig cells, reflecting alternations in cell composition and function. Although the overall proportion of Sertoli cells declined, their relative abundance among somatic cells increased. Conclusions This study demonstrates at the single-cell level that ionizing radiation significantly disrupts male reproductive system function by depleting germ cells and reshaping the somatic cell landscape, thereby providing a molecular foundation for deeper understanding and targeted intervention of radiation-induced reproductive toxicity. |
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