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

The 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 demonstrate that mouse 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. Spermatozoa derived from Bbof1-knockout mice 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 and is also required for their stability. Our findings in mice suggest that Bbof1 could also be essential for human sperm motility and male fertility, thus is a novel potential candidate gene for asthenozoospermia diagnosis.

Automated summary

BBOF1 plays a crucial role in maintaining the integrity and function of the sperm flagellum through its interaction with ODF2 and MNS1 proteins. It is expressed exclusively in male germ cells and is required for sperm motility and male fertility. It has the potential to be a novel candidate gene for diagnosing asthenozoospermia.