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10.4103/aja202620
Abscopal effect-induced acephalic spermatozoa and testicular dysfunction implicate Cep112 and PI3K/Akt-mTOR signaling
Zhi-Xiang Mao1
Li-Xiu Lv2
Jin-Jin Chu3
Ming-Zheng Li1
Yao-Yao Dong4
Fei Xue5
Xiang-Long Li1
Xiao-Ji Lin5
Wen-Jian Guo5
Wen-Jie Sun1
Cong-Ying Xie1,6
C Yan Cheng7,
Lin-Xi Li1,
1Zhejiang Engineering Research Center for Innovation and Application of Intelligent Radiotherapy Technology, Zhejiang-Hong Kong Precision Theranostics of Thoracic Tumors Joint Laboratory, Wenzhou Key Laboratory of Basic Science and Translational Research of Radiation Oncology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, China
2Research Center of Basic Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, China
3Ningbo Clinical Pathology Diagnosis Center, Ningbo 315000, China
4Department of Pharmacy, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, China
5Department of Oncology and Radiotherapy, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, China
6Department of Radiation and Medical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
7Department of Urology and Andrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China
Correspondence: Dr. LX Li (lilinxi1234@163.com) or Dr. CY Cheng (l211064@zju.edu.cn)
Received: 23 November 2025; Accepted: 19 April 2026; published online: 20 October 2026
| Abstract |
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The abscopal effect, a systemic phenomenon induced by localized irradiation and associated with inflammatory factor activation, has attracted significant interest in the context of radiotherapy combined with immunotherapy. While recognized as potentially beneficial in oncology, this effect can have detrimental off-target consequences. The underlying mechanisms for abscopal effect-induced testicular dysfunction remain unclear. In this study, we observed a pronounced testicular disruption phenotype characterized by abnormalities in meiosis, blood-testis barrier integrity, and spermatid orientation. Notably, we report the novel finding that the abscopal effect can induce acephalic spermatozoa (headless sperm). Transcriptional analysis by quantitative real-time polymerase chain reaction revealed the dysregulation of the expression of centrosomal proteins, known regulators of meiosis and spermiogenesis. By employing RNA interference to knock down centrosomal protein 112 (Cep112), we demonstrated its critical role in spermiogenesis and established its close association with the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) and mechanistic target of rapamycin/ribosomal protein S6 (mTOR/rpS6) signaling pathways. Our findings indicate that Cep112 mediates cytoskeletal organization in testes and sperm formation via the PI3K/Akt and mTOR/rpS6 pathways, suggesting that Cep112 significantly contributes to abscopal effect-induced spermatogenic dysfunction.
Keywords: abscopal effect; centrosomal protein 112; sperm; spermatogenesis; testis
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