Down-regulation of centrosomal Cep290 contributes to testes aging via single cell RNA-Seq data analysis

Male reproductive aging represents a significant global health concern that profoundly impacts men's well-being. While existing studies have demonstrated that the structure and function of centrosomes are compromised in aging human oocytes, the alterations in centrosomal characteristics during the aging process of male testicular cells remain insufficiently elucidated. This study aims to elucidate the functional alterations of centrosomes in aged testicular tissues, identify key molecular targets associated with these changes, and investigate how centrosomal dysfunction affects sperm motility through single-cell analysis technologies. Human and mouse single-cell RNA sequencing datasets were obtained from the OMIX and GEO databases, respectively. Analytical methods included pseudo-time trajectory analysis, intercellular communication inference, hdWGCNA (hybrid weighted gene co-expression network analysis), and SCEIN (single-cell expression interaction network) construction. Our data showed that abnormal sperms were significantly increased in aging epididymidis when compared to that in young ones. Futher single-cell RNA sequence analysis indicates a significant decline in centrosome function in aged testes compared to young ones, particularly in ciliary assembly and centrosome duplication processes. Early spermatocytes were identified as the earliest stage at which centrosomal functional changes occur during spermatogenesis. A conserved pattern of centrosome dysfunction was observed in aging human testes. Cep290 was identified as a core regulatory gene associated with centrosomal changes in aging testes. Further analysis indicates that Brac1 might be a key upstream positive regulator of Cep290. Our results indicate that dysfunctional centrosome is attributed to the dysregulation of Cep290 expression in aged germ cells.