Integrative Analysis of KIF17 and FHL5 Confirms their Role in Spermatogenic Arrest and Male Infertility

Spermatogenic arrest is a major cause of male infertility characterized by disruption of germ cell development. This condition is attributed to genetic factors, but the underlying molecular mechanisms remain incompletely understood. Therefore, this study aims to investigate the association of KIF17 rs13375609 and FHL5 rs2273621 variants with spermatogenic arrest using an integrative method combining genetic analysis, mRNA expression profiling, and histopathological evaluation. Genotyping was performed using peripheral blood samples, while gene expression and histopathological analyses were conducted on FFPE testicular tissue. The results showed no significant association between KIF17 rs13375609 and spermatogenic arrest. Meanwhile, FHL5 rs2273621 was significantly associated with GG genotype, featuring a protective effect, and the A allele correlated with increased risk. FHL5 expression increased in higher Johnsen score groups, supporting its role in normal spermatogenesis. In this study, KIF17 expression presented a non-significant trend. In conclusion, FHL5 may play a more prominent role in spermatogenic regulation, potentially through CREM-mediated transcription, while KIF17 contributes to intracellular transport processes in spermiogenesis. This integrative analysis provides insight into the molecular mechanisms underlying spermatogenic arrest and underscores the potential of FHL5 as a candidate molecular marker in male infertility.