The role of specific centrosomal protein dysfunctions in specific sperm defects

Zhuoming Xu^1,#, Jialu Xin^2,#, Weiqing Xu¹, Guicheng Liu¹, Liang Dong^2,*, Xujun Yu^3,*
1 TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
2 School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
3 The Second Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
* Corresponding Author: Liang Dong. Email: email ; Xujun Yu. Email: email
# These authors contributed equally to this work

Canadian Journal of Urology https://doi.org/10.32604/cju.2026.077071

Received 01 December 2025; Accepted 01 April 2026; Published online 15 June 2026

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Abstract

The centrosome is essential for preserving germ-cell integrity across evolution and for safeguarding paternal inheritance in humans. This evolutionarily conserved subcellular structure serves as the primary microtubule-organizing center in mammalian cells, coordinating the assembly of microtubule-based structures that mediate sperm head–neck coupling, flagellar biogenesis and other cytoskeletal rearrangements required for spermatogenesis and early embryogenesis. A rapidly expanding literature now implicates centrosomal proteins in male infertility: structural or functional defects of the centrosome consistently correlate with aberrant sperm morphology, motility failure and distinct pathological phenotypes. The research objective is to review the role of centrosomal protein dysfunctions in specific sperm defects and to discuss their molecular mechanisms and clinical implications for male infertility. Here we review infertility-linked mutations in a select group of centrosomal proteins and dissect their molecular roles in centriole duplication, axonemal assembly and head–neck connection. We outline how pathogenic variants disrupt the spermatogenic program, ultimately producing morphologically abnormal, immotile spermatozoa. Finally, we discuss the clinical utility of these findings for genetic counselling and predictive assessment of male fertility, and we place them in an evolutionary context by highlighting the conserved ultrastructural features of human spermatozoa that depend on an intact centrosome.