Genetic deficiency of EXOSC10 ribonuclease disrupts spermatogenesis and male fertility in mice

Male germ cell meiosis is essential for the generation of haploid spermatozoa in mammals. Oocyte-specific KO of Exosc10 results in female subfertility by impairing germinal vesicle breakdown and disrupting the transcriptome during oocyte maturation. However, the involvement of EXOSC10 in the regulation of male germ cell meiosis remains poorly understood. This study explores the pivotal role of EXOSC10 ribonuclease in male germ cell meiosis in mice. Conditional deletion of Exosc10 in premeiotic germ cells impedes spermatogonial differentiation and obstructs meiotic progression in spermatocytes, characterized by abnormal synapsis and defective meiotic recombination. These disruptions lead to heightened apoptosis, defective meiosis, compromised spermatogenesis, and resultant male sterility. Single-cell RNA-Seq analysis further corroborates these meiotic defects, demonstrating that Exosc10 deficiency disrupts RNA metabolism, misregulates meiotic gene expression, and impairs rRNA processing. Consequently, the meiotic process is compromised, spermatogenesis is disrupted, and male infertility ensues. Collectively, these findings underscore the critical role of EXOSC10 in maintaining a proper transcriptome during spermatocyte meiotic progression, thereby ensuring normal spermatogenesis and male fertility.