Protective Efficacy of Met-Ser-Arg Against Irradiation-Related Testicular Injury

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ID: 315130
2026
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Abstract
Ionizing radiation poses a significant risk to male fertility by inducing testicular damage, yet effective protective strategies remain limited. The tripeptide Met-Ser-Arg (MSA) has demonstrated potential in alleviating radiation-induced oxidative stress and lipid metabolic disorders, prompting investigation into its protective effects on the male reproductive system. Male BALB/c mice were exposed to X-ray irradiation (0.5 Gy/day for 5 days) to establish a testicular injury model, followed by MSA treatment. Testicular structure and function were evaluated through histology, electron microscopy, computer-assisted sperm analysis (CASA), and quantitative PCR. MSA significantly alleviated radiation-induced testicular damage, restoring the structural integrity and function of spermatogenesis tubules while increasing both the height of the spermatogenic epithelium and germ cell number. Sperm quality and motility were markedly improved, and the expression of several sperm cell molecular markers was favorably adjusted. Mechanistic investigations revealed that MSA regulated lipid metabolism by upregulating fatty acid β-oxidation enzymes, including ACSL3 and CPT1A, while downregulating the lipid synthase DGAT2, thereby reducing lipid droplet accumulation. MSA also attenuated radiation-induced reactive oxygen species and malondialdehyde levels, enhanced antioxidant capacity through upregulation of NRF2 and HO-1, and preserved mitochondrial structure and function via upregulation of PGC1A. Furthermore, MSA reduced apoptosis by lowering the levels of Cleaved-caspase 3 and γH2AX. Collectively, these findings demonstrate that MSA ameliorates radiation-induced testicular injury and improves sperm quality through coordinated regulation of lipid metabolism, antioxidant pathway activation, mitochondrial protection, and apoptosis inhibition, providing a theoretical basis for its potential clinical application in the context of radiotherapy.
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Authors Huapei Wang, Nengliang Duan, Long Sun, Yuanshuai Ran, Luo Ya, Yufan Xu, Fengmei Cui, Yao Yan, Boxin Xue, Q Chen, Xiaolong Liu
Journal biology of reproduction
Year 2026
DOI
10.1093/biolre/ioag110
URL
https://doi.org/10.1093/biolre/ioag110
Keywords Keywords not found

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