College of Life Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, China.
Zhejiang University-University of Edinburgh Institute (ZJU-UoE Institute), Zhejiang University School of Medicine, Zhejiang University, 718 East Haizhou Road, Haining, 314400, China.
Cell Mol Life Sci. 2023 May 17;80(6):152. doi: 10.1007/s00018-023-04800-0.
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.
精子鞭毛是一种特殊的运动性纤毛，由典型的“9+2”轴丝结构和周边轴丝结构组成，如外周致密纤维（ODF）。这种鞭毛排列对于精子的运动和受精至关重要。然而，轴丝完整性与 ODF 的关联仍知之甚少。在这里，我们证明了小鼠 BBOF1 可以与轴丝成分 MNS1 和 ODF 蛋白 ODF2 相互作用，并且对于精子鞭毛轴丝的维持和雄性生育能力是必需的。BBOF1 仅在从粗线期开始的雄性生殖细胞中表达，并在精子轴丝部分检测到。源自 Bbof1 敲除小鼠的精子表现出正常的形态，但是由于某些微管二联体的缺失导致运动能力降低，从而导致无法使成熟卵子受精。此外，发现 BBOF1 与 ODF2 和 MNS1 相互作用，并且对于它们的稳定性也是必需的。我们在小鼠中的发现表明，Bbof1 对于人类精子的运动和男性生育能力也可能是必不可少的，因此是弱精症诊断的一个新的潜在候选基因。
