Sperm-associated antigen 6 (SPAG6) as a potential marker of sperm function in diagnosing male infertility

Background: While male infertility has become a significant global health concern, conventional analysis of semen has not made progress in the detection of contraindicated molecular biomarkers, such as sperm-associated antigen 6 (SPAG6), which is a protein involved in axonemal structure and flagellar motility. Hypothesis: Expression of SPAG6 correlates with sperm motility and structural integrity. This means that its dysregulation may serve as a molecular indicator of impaired sperm performance. Methods: A comprehensive review of recent studies was conducted with a focus on SPAG6’s molecular characteristics, expression patterns in normal versus abnormal spermatozoa, and the role it plays in motility-related disorders. To assess SPAG6’s diagnostic value, experimental data from immunohistochemical analyses, gene knockout models, and clinical semen samples were evaluated. Findings: SPAG6 is consistently expressed in the central apparatus of the sperm axoneme and dysregulation correlates to abnormal flagellar architecture, often resulting in impairment of motility and asthenozoospermia. This highlights its utility as a molecular marker for diagnosis of sperm dysfunction, and its potential to guide targeted therapeutic strategies. Conclusion: SPAG6 is a promising biomarker to evaluate sperm function. Its expression level offers greater mechanistic insights than can be achieved in conventional semen analysis. Further validation in clinical settings may establish its role in improving the precision of diagnosis to guide targeted treatment for male infertility.