Microtubule-associated CCDC112 is essential for spermiogenesis and male fertility in mice

Abstract Defective sperm motility is frequently associated with male infertility. The immotile short-tail sperm (ISTS) defect is a rare condition in which most sperm cells have abnormally short tails, impairing their motility and leading to infertility. Despite its implications, the genetic factors related to the ISTS defect remain largely unclear. In this study, we identify coiled-coil domain-containing 112 (CCDC112) as a critical factor for sperm tail formation. CCDC112 can associate with microtubules and interact with multiple centrosomal proteins, including PCM1, TEX9, and taxilin. Disruption of CCDC112 expression profoundly affects the cellular distribution of PCM1. Interestingly, the knockout of Ccdc112 in mice impacts spermiogenesis, resulting in the ISTS defect and ultimately causing male infertility. Furthermore, quantitative proteomic analysis highlights the essential role of CCDC112 in regulating axonemal microtubule inner proteins. We thus characterize CCDC112 as a microtubule-associated protein and substantiate its genetic link to ISTS-related male infertility.