Abstract
Asthenozoospermia, characterized by low sperm motility, is one of the most common causes of male infertility. While many intrinsic and extrinsic factors are involved in the etiology of asthenozoospermia, the molecular basis of this condition remains unclear. Since sperm motility results from a complex flagellar structure, an in-depth proteomic analysis of the sperm tail can uncover mechanisms underlying asthenozoospermia. This study quantified the proteomic profile of 40 asthenozoospermic sperm tails and 40 controls using TMT-LC–MS/MS. Overall, 2140 proteins were identified and quantified where 156 proteins have not been described earlier in sperm tail. There were 409 differentially expressed proteins (250 upregulated and 159 downregulated) in asthenozoospermia which by far is the highest number reported earlier. Further, bioinformatics analysis revealed several biological processes, including mitochondrial-related energy production, oxidative phosphorylation (OXPHOS), citric acid cycle (CAC), cytoskeleton, stress response, and protein metabolism altered in asthenozoospermic sperm tail samples. Collectively, our findings reveal the importance of mitochondrial energy production and induced stress response as potential mechanisms involved in the loss of sperm motility in asthenozoospermia.
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Acknowledgements
We express our heartfelt appreciation to Morteza Abyadeh for his great help in writing this manuscript. We also thank Mehdi Alikhani for helping with preliminary data analysis and providing valuable contributions.
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This work was supported by a research grant (91000398) from the Royan Institute.
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TRT and ASH conceived the idea and designed the study. SM performed mass spectrometry and bioinformatic analysis. TRT, SM, and PR carried out the experiments. The first draft was written by TRT and completed by MNB. All authors read and edited the final version of the manuscript.
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This case–control study was approved by the Institutional Ethics Committee of Royan Institute, Tehran, Iran (IR.ACECR.ROYAN.REC.1391.398).
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Mirshahvaladi, S., Topraggaleh, T.R., Bucak, M.N. et al. Quantitative proteomics of sperm tail in asthenozoospermic patients: exploring the molecular pathways affecting sperm motility. Cell Tissue Res 392, 793–810 (2023). https://doi.org/10.1007/s00441-023-03744-y
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DOI: https://doi.org/10.1007/s00441-023-03744-y