Oxidative Stress-Associated Alterations in Sperm ACTL7A Expression and Function in Men With Varicocele

Actin-like 7A (ACTL7A) is a testis-specific cytoskeletal protein essential for spermiogenesis, acrosome formation, and oocyte activation. Given its critical role in sperm integrity and fertilization, ACTL7A protein may be particularly susceptible to oxidative and thermal stress associated with varicocele. This study aimed to evaluate ACTL7A gene, and protein expression in the sperm of infertile men with varicocele.

Semen samples from infertile men with varicocele (n = 35) and fertile controls (n = 35) were assessed for standard sperm parameters (WHO 2021), redox status (2',7'-dichlorodihydrofluorescein diacetate [DCFH-DA] and BODIPY probes), chromatin packaging (Chromomycin A3 [CMA3] and Aniline Blue staining), DNA integrity (Sperm Chromatin Structure Assay [SCSA]), ACTL7A gene, and protein expression (quantitative real-time PCR and Western blotting).

Compared to fertile controls, the varicocele group exhibited significantly lower sperm quality, elevated oxidative stress, increased lipid peroxidation, and greater chromatin immaturity and DNA fragmentation (p < 0.01). Notably, ACTL7A gene and ACTL7A protein expression levels were significantly reduced (p < 0.05), with inverse correlations observed between ACTL7A gene and markers of chromatin packaging defects, including protamine deficiency and residual histones (p < 0.05).

ACTL7A gene expression and ACTL7A protein are significantly reduced in sperm from men with varicocele, likely causing defective chromatin remodeling and abnormal sperm head formation. This study first links varicocele-associated oxidative stress to ACTL7A, suggesting its potential as a biomarker of testicular dysfunction. Future research should explore whether interventions like antioxidant therapy, varicocelectomy, or varicocele severity and duration improve sperm quality and reproductive outcomes.