Ionizing radiation-induced disruption of Rela-Bclaf1-spliceosome regulatory axis in primary spermatocytes causing spermatogenesis dysfunction
Abstract Introduction Ionizing radiation (IR) poses a significant threat to male fertility by inducing substantial changes in the testis, yet the mechanisms underlying IR-induced spermatogenesis disorders remain poorly understood, necessitating the development of more effective radioprotective agent...
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| Format: | Article |
| Language: | English |
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BMC
2025-01-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-025-02067-5 |
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| author | Hongjian Zhou Zhipeng Xu Chun Jiang Qiuyue Wu Chuanyue Zhang Zhenyu Liu Xiaoxue Zhang Weiwei Li Yujia Pang Jing Zhang Wenju Pan Min Chen Xinyi Xia |
| author_facet | Hongjian Zhou Zhipeng Xu Chun Jiang Qiuyue Wu Chuanyue Zhang Zhenyu Liu Xiaoxue Zhang Weiwei Li Yujia Pang Jing Zhang Wenju Pan Min Chen Xinyi Xia |
| author_sort | Hongjian Zhou |
| collection | DOAJ |
| description | Abstract Introduction Ionizing radiation (IR) poses a significant threat to male fertility by inducing substantial changes in the testis, yet the mechanisms underlying IR-induced spermatogenesis disorders remain poorly understood, necessitating the development of more effective radioprotective agents. Methods We employed Bulk RNA-seq and single-cell RNA-seq (scRNA-seq) on Balb/c mice testes models following IR exposure to assess cellular and transcriptional alterations. Histological examination, sperm concentration and motility analysis, Western blotting (WB), and reverse transcription quantitative PCR (RT-qPCR) were used to evaluate testicular injury. The therapeutic potential of NF-κB agonists was investigated in an IR-induced spermatogenesis disorder model. Results A 6 Gy IR dose induced spermatogenesis disorder and suppressed the spliceosome pathway, predominantly affecting the cell abundance of spermatogonia and primary spermatocytes. Bioinformatics analysis revealed that IR induced splicing disorders in differentiation-related genes, thereby impairing the differentiation ability of primary spermatocytes. Mechanistically, This IR-induced disruption was linked to IR-induced inhibition of NF-κB/Rela and Bclaf1 activity. Notably, NF-κB agonists were found to ameliorate this damage via upregulating Bclaf1 and spliceosome-related genes expression, thereby normalizing splicing patterns and rescuing IR-induced spermatogenesis disorders. Conclusion This study reveals a novel IR-mediated Rela-Bclaf1-spliceosome regulatory axis in primary spermatocytes and propose Rela as a potential drug target for mitigating IR-induced spermatogenesis disorders. This study not only provides new insights for further research into IR-induced damage and spermatogenic disorders caused by other factors, but also offers potential therapeutic strategies for developing radioprotective agents in cancer radiotherapy. |
| format | Article |
| id | doaj-art-a972f60ee2a743bdb9c238dbdd0ce726 |
| institution | Kabale University |
| issn | 1478-811X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj-art-a972f60ee2a743bdb9c238dbdd0ce7262025-02-02T12:34:30ZengBMCCell Communication and Signaling1478-811X2025-01-0123112110.1186/s12964-025-02067-5Ionizing radiation-induced disruption of Rela-Bclaf1-spliceosome regulatory axis in primary spermatocytes causing spermatogenesis dysfunctionHongjian Zhou0Zhipeng Xu1Chun Jiang2Qiuyue Wu3Chuanyue Zhang4Zhenyu Liu5Xiaoxue Zhang6Weiwei Li7Yujia Pang8Jing Zhang9Wenju Pan10Min Chen11Xinyi Xia12Institute of Laboratory Medicine, Jinling Hospital, First School of Clinical Medicine, Nanjing University School of Medicine, Southern Medical UniversityCenter for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical SchoolInstitute of Laboratory Medicine, Jinling Hospital, First School of Clinical Medicine, Nanjing University School of Medicine, Southern Medical UniversityInstitute of Laboratory Medicine, Jinling Hospital, First School of Clinical Medicine, Nanjing University School of Medicine, Southern Medical UniversityInstitute of Laboratory Medicine, Jinling Hospital, First School of Clinical Medicine, Nanjing University School of Medicine, Southern Medical UniversityInstitute of Laboratory Medicine, Jinling Hospital, First School of Clinical Medicine, Nanjing University School of Medicine, Southern Medical UniversityInstitute of Laboratory Medicine, Jinling Hospital, First School of Clinical Medicine, Nanjing University School of Medicine, Southern Medical UniversityInstitute of Laboratory Medicine, Jinling Hospital, First School of Clinical Medicine, Nanjing University School of Medicine, Southern Medical UniversityInstitute of Laboratory Medicine, Jinling Hospital, First School of Clinical Medicine, Nanjing University School of Medicine, Southern Medical UniversityInstitute of Laboratory Medicine, Jinling Hospital, First School of Clinical Medicine, Nanjing University School of Medicine, Southern Medical UniversityInstitute of Laboratory Medicine, Jinling Hospital, First School of Clinical Medicine, Nanjing University School of Medicine, Southern Medical UniversityInstitute of Laboratory Medicine, Jinling Hospital, First School of Clinical Medicine, Nanjing University School of Medicine, Southern Medical UniversityInstitute of Laboratory Medicine, Jinling Hospital, First School of Clinical Medicine, Nanjing University School of Medicine, Southern Medical UniversityAbstract Introduction Ionizing radiation (IR) poses a significant threat to male fertility by inducing substantial changes in the testis, yet the mechanisms underlying IR-induced spermatogenesis disorders remain poorly understood, necessitating the development of more effective radioprotective agents. Methods We employed Bulk RNA-seq and single-cell RNA-seq (scRNA-seq) on Balb/c mice testes models following IR exposure to assess cellular and transcriptional alterations. Histological examination, sperm concentration and motility analysis, Western blotting (WB), and reverse transcription quantitative PCR (RT-qPCR) were used to evaluate testicular injury. The therapeutic potential of NF-κB agonists was investigated in an IR-induced spermatogenesis disorder model. Results A 6 Gy IR dose induced spermatogenesis disorder and suppressed the spliceosome pathway, predominantly affecting the cell abundance of spermatogonia and primary spermatocytes. Bioinformatics analysis revealed that IR induced splicing disorders in differentiation-related genes, thereby impairing the differentiation ability of primary spermatocytes. Mechanistically, This IR-induced disruption was linked to IR-induced inhibition of NF-κB/Rela and Bclaf1 activity. Notably, NF-κB agonists were found to ameliorate this damage via upregulating Bclaf1 and spliceosome-related genes expression, thereby normalizing splicing patterns and rescuing IR-induced spermatogenesis disorders. Conclusion This study reveals a novel IR-mediated Rela-Bclaf1-spliceosome regulatory axis in primary spermatocytes and propose Rela as a potential drug target for mitigating IR-induced spermatogenesis disorders. This study not only provides new insights for further research into IR-induced damage and spermatogenic disorders caused by other factors, but also offers potential therapeutic strategies for developing radioprotective agents in cancer radiotherapy.https://doi.org/10.1186/s12964-025-02067-5Ionizing radiationSpermatogenesis dysfunctionscRNA-seqSpliceosomeBclaf1Rela |
| spellingShingle | Hongjian Zhou Zhipeng Xu Chun Jiang Qiuyue Wu Chuanyue Zhang Zhenyu Liu Xiaoxue Zhang Weiwei Li Yujia Pang Jing Zhang Wenju Pan Min Chen Xinyi Xia Ionizing radiation-induced disruption of Rela-Bclaf1-spliceosome regulatory axis in primary spermatocytes causing spermatogenesis dysfunction Cell Communication and Signaling Ionizing radiation Spermatogenesis dysfunction scRNA-seq Spliceosome Bclaf1 Rela |
| title | Ionizing radiation-induced disruption of Rela-Bclaf1-spliceosome regulatory axis in primary spermatocytes causing spermatogenesis dysfunction |
| title_full | Ionizing radiation-induced disruption of Rela-Bclaf1-spliceosome regulatory axis in primary spermatocytes causing spermatogenesis dysfunction |
| title_fullStr | Ionizing radiation-induced disruption of Rela-Bclaf1-spliceosome regulatory axis in primary spermatocytes causing spermatogenesis dysfunction |
| title_full_unstemmed | Ionizing radiation-induced disruption of Rela-Bclaf1-spliceosome regulatory axis in primary spermatocytes causing spermatogenesis dysfunction |
| title_short | Ionizing radiation-induced disruption of Rela-Bclaf1-spliceosome regulatory axis in primary spermatocytes causing spermatogenesis dysfunction |
| title_sort | ionizing radiation induced disruption of rela bclaf1 spliceosome regulatory axis in primary spermatocytes causing spermatogenesis dysfunction |
| topic | Ionizing radiation Spermatogenesis dysfunction scRNA-seq Spliceosome Bclaf1 Rela |
| url | https://doi.org/10.1186/s12964-025-02067-5 |
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