| 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].Chinese Journal of Radiological Medicine and Protection,2026,46(1):29-35 |
| Single-cell transcriptome analysis of testes following ionizing radiation exposure and preliminary exploration of reproductive toxicity mechanisms |
| Received:December 30, 2024 |
| DOI：10.3760/cma.j.cn112271-20241230-00500 |
| KeyWords:Ionizing radiation Testicular injury Single-cell sequencing Leydig cell |
| FundProject: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) |
| Author Name | Affiliation | E-mail | | Wang Huapei | Department of Urology, Second Hospital Affiliated to Soochow University, Suzhou 215000, China | | | Duan Nengliang | Department of Urology, Second Hospital Affiliated to Soochow University, Suzhou 215000, China | | | Gao Zhixiang | Department of Urology, Second Hospital Affiliated to Soochow University, Suzhou 215000, China | | | Ran Yuanshuai | Department of Urology, Second Hospital Affiliated to Soochow University, Suzhou 215000, China | | | Sun Long | Department of Urology, Second Hospital Affiliated to Soochow University, Suzhou 215000, China | | | Gong Shiwei | Department of Urology, Second Hospital Affiliated to Soochow University, Suzhou 215000, China | | | Cui Fengmei | School of Radiation Medicine and Protection, Soochow University, Suzhou 215000, China | | | Chen Qiu | School of Radiation Medicine and Protection, Soochow University, Suzhou 215000, China | liuxiaolong2005@suda.edu.cn | | Xue Boxin | Department of Urology, Second Hospital Affiliated to Soochow University, Suzhou 215000, China | | | Liu Xiaolong | Department of Urology, Second Hospital Affiliated to Soochow University, Suzhou 215000, China | |
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| Abstract:: |
| 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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