Potential Biomarkers and Therapeutic Targets for Ferroptosis in Spermatogenic Dysfunction

Abstract

Ferroptosis plays a pivotal role in cellular demise, encompassing processes involving germ cells, and it is intricately associated with spermatogenesis. However, the role of ferritinase-associated genes in spermatogenic dysfunction has not been comprehensively elucidated. In this study, we retrieved relevant information and Ferritin-Related Genes (FRGs) associated with spermatogenic dysfunction from the Gene Expression Omnibus (GEO) and the FerrDb ferritin database, resulting in a total of 24 Differentially Expressed Ferritin-Related Genes (DE-FRGs) linked to spermatogenic dysfunction. Subsequently, the application of LASSO and SVM-RFE algorithms identified KLHDC3 from the pool of DE-FRGs as the candidate marker gene. Subsequent functional enrichment analysis indicated that the identified candidate marker gene may function through involvement in regulating ferroptosis, autophagy, apoptosis, and various kinases in the pathogenesis of spermatogenic dysfunction. The constructed ceRNA network revealed intricate regulatory relationships centered around the candidate marker gene. We have established a diagnostic efficacy and offered insights into the mechanisms underlying spermatogenic dysfunction. Prior to clinical implementation, further investigation is warranted to validate its diagnostic value for spermatogenic dysfunction.