Abstract:
The integrity of the sperm flagellum is essential for normal sperm function. Defects in the flagellum can lead to male infertility, however, the mechanisms underlying this relationship are largely unknown. CCDC181, a protein containing a coiled-coil domain, localizes on the sperm flagella and the basal parts of motile cilia. The roles of CCDC181 in flagellum biogenesis have remained elusive. In this study, Ccdc181 knockout mice were generated. The absence of CCDC181 resulted in defective sperm head shaping and flagellum formation. Ccdc181 knockout mice exhibited extremely low sperm counts, completely aberrant sperm morphologies, nearly absent sperm motility, and the typical multiple morphological abnormalities of the flagella (MMAF). Additionally, we identified that CCDC181 can interact with the MMAF-related protein LRRC46 and regulate the localization of LRRC46 in sperm flagella. Therefore, our findings suggest that CCDC181 plays a crucial role in both manchette formation and sperm flagellum biogenesis.
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