TTC6-Mediated Stabilization of the Flagellum Annulus Ensures the Rapid and Directed Motion of Sperm
Ziqi Wang,
Kailun Fang,
Yanling Wan,
Yingying Yin,
Mengjing Li,
Ke Xu,
Tongtong Li,
Yongzhi Cao,
Yue Lv,
Gang Lu,
Hongbin Liu,
Tao Huang
Affiliations
Ziqi Wang
Center for Reproductive Medicine, Shandong University, Jinan 250012, China
Kailun Fang
Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China
Yanling Wan
Center for Reproductive Medicine, Shandong University, Jinan 250012, China
Yingying Yin
Center for Reproductive Medicine, Shandong University, Jinan 250012, China
Mengjing Li
Center for Reproductive Medicine, Shandong University, Jinan 250012, China
Ke Xu
Center for Reproductive Medicine, Shandong University, Jinan 250012, China
Tongtong Li
Center for Reproductive Medicine, Shandong University, Jinan 250012, China
Yongzhi Cao
Center for Reproductive Medicine, Shandong University, Jinan 250012, China
Yue Lv
CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China
Gang Lu
Center for Reproductive Medicine, Shandong University, Jinan 250012, China
Hongbin Liu
Center for Reproductive Medicine, Shandong University, Jinan 250012, China
Tao Huang
Center for Reproductive Medicine, Shandong University, Jinan 250012, China
Sperm motility and structural integrity are essential for successful fertilization in vivo, and any hindrance of the correct assembly of the axoneme and peri-axonemal structures in the sperm flagellum can lead to fertility problems. While there has been considerable advancement in studying diseases related to the flagellum, the underlying mechanisms that control sperm movement are not yet fully understood. In this study, we reveal that the tetratricopeptide repeat protein 6 (Ttc6) gene, expressed mainly in the testes, plays a crucial role in maintaining male fertility in mice. We further demonstrate that the knockout of Ttc6 in mice results in decreased sperm motility and induces an abnormal circular swimming pattern, consequently leading to male subfertility. Morphological analysis showed an atypical hairpin-like appearance of the spermatozoa, and ultrastructural studies showed unsheathed flagella at the juncture between the midpiece and principal piece. Collectively, these findings suggest that TTC6 plays an essential role in maintaining the stability of the annulus region of the sperm flagellum, thus ensuring the swift and directed motion of sperm.
