Ionizing Radiation-induced Disruption of Rela-Bclaf1-spliceosome Regulatory Axis in Primary Spermatocytes Causing Spermatogenesis Dysfunction

Overview

Journal Cell Commun Signal

Publisher Biomed Central

Date 2025 Jan 31

PMID 39891142

Authors

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

Affiliations

Soon will be listed here.

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.

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