Abscopal effect-induced acephalic spermatozoa and testicular dysfunction implicate Cep112 and PI3K/Akt-mTOR signaling.

Abstract

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.