RPS14 as an aging-related biomarker for early-onset alterations of testicular senescence-associated genes in spermatogenic dysfunction at childbearing age

The early-onset transcriptional phenotype of senescence has been revealed in spermatogenic dysfunctional testes of patients at childbearing age. However, limited studies have reported the biomarker and function of testicular senescence-associated genes (SAGs) in the spermatogenic dysfunction of young men. In this study, two single-cell RNA sequencing (scRNA-seq) datasets, three bulk microarray datasets, and testicular tissue from older mice, older male, patients at childbearing age with full spermatogenesis or spermatogenic dysfunction were employed to recognize the aging-related biomarker for early-onset alterations of testicular SAGs. We found RPS14, an upregulated testicular SAGs in testes of older men, was an important biomarker for early-onset alterations of testicular SAG in young spermatogenic dysfunctional testes. RPS14 was significantly upregulated in young patients' testes with spermatogenic dysfunction. Importantly, RPS14 showed significant correlation with Johnsen scores and follicle-stimulating hormone levels and had potential predictive value in sperm retrieval surgery. Besides, RPS14 was found to be deeply involved in the testicular immune microenvironment and significantly correlated with testicular mast cells. The scRNA-seq analyses and immunofluorescence illustrated the partially similar expression pattern and distribution of RPS14 in testes of both older males and young males with spermatogenic dysfunction. Moreover, the ribosome pathway might be the core mechanism through which this gene regulates the function of testicular cells. RPS14 was shown to be an aging-related biomarker, which might be involved in the pathogenesis of spermatogenic dysfunction of young patients. The findings might offer a potential diagnostic marker as well as a therapeutic target for young patients diagnosed with male infertility.