EXOSC10, an Exosome-Associated RNase, Is Essential for Mouse Spermatogonia Maintenance and Spermatogenesis

Mammalian spermatogenesis comprises three phases: the mitotic phase of spermatogonia (involving self-renewal and proliferation), the meiotic phase of spermatocytes (producing haploid round spermatids), and the spermiogenic phase (transforming round spermatids into spermatozoa). This process depends critically on maintaining a normal transcriptome and proteome. While recent studies demonstrated that conditional knockout of Exosc10 in male germ cells prior to meiosis disrupts meiosis, causing spermatogenic defects and male infertility, the role of EXOSC10 in spermatogonial maintenance remained unknown. This study reveals the critical role of EXOSC10 in maintaining mouse spermatogonia. Knockout of Exosc10 in embryonic (E15.5) male germ cells using Ddx4-Cre mice disrupts spermatogonial maintenance. This is manifested by reduced germ cell proliferation, arrested spermatogenesis, failed sperm production, and consequent male infertility. Transcriptomic and proteomic analyses confirmed that Exosc10 deficiency disrupts the expression of genes and proteins associated with spermatogenesis, ribosome biogenesis, germline stem cell maintenance, and regulation of reproductive processes, thereby impairing spermatogonial maintenance and blocking spermatogenesis. In summary, this study highlights that EXOSC10 safeguards normal sperm production and male fertility by maintaining the transcriptome and proteome essential for spermatogenesis, particularly at the spermatogonial stage.