Otud6a Knockout Leads to Male Subfertility in Mice

ABSTRACT Ovarian tumor ubiquitinating 6A (OTUD6A) is a deubiquitinating enzyme whose aberrant expression has been linked to various diseases, including inflammation and prostate cancer. Research indicates that deubiquitinating enzymes (DUBs) play a significant role in spermatogenesis in mice. However, the role of OTUD6A in spermatogenesis remains unclear. To investigate the function of OTUD6A in mouse spermatogenesis, we generated Otud6a‐ knockout mice using the CRISPR/Cas9 system. Our results showed that OTUD6A is predominantly expressed in the testis and localized to the cytoplasm of spermatogonia and spermatocytes. Although no significant differences were observed in testicular size or morphology between Otud6a‐ knockout and wild‐type mice, the knockout mice exhibited increased germ cell apoptosis, decreased epididymal sperm counts, abnormalities in sperm motility and subfertility. These findings indicate that Otud6a‐ knockout leads to male subfertility in mice.