BBOF1 is required for sperm motility and male fertility by stabilizing the flagellar axoneme

Abstract

AbstractThe sperm flagellum is a specialized type of motile cilium composed of a typical “9 + 2” axonemal structure with peri-axonemal structures, such as outer dense fibers (ODFs). This flagellar arrangement is crucial for sperm movement and fertilization. However, the association of axonemal integrity with ODFs remains poorly understood. Here, we demonstrat that mammalian BBOF1 could interact with both MNS1, an axonemal component, and ODF2, an ODF protein, and is required for sperm flagellar axoneme maintenance and male fertility. BBOF1 is expressed exclusively in male germ cells from the pachytene stage onwards and is detected in sperm axoneme fraction. Sperm derived fromBbof1-knockout males exhibit a normal morphology, however reduced motility due to the absence of certain microtubule doublets, resulting in the failure to fertilize mature oocytes. Furthermore, BBOF1 is found to interact with ODF2 and MNS1, which is also required for their stability. Our findings suggest that BBOF1 is a novel potential marker for asthenozoospermia diagnosis.