CCDC176 stabilizes microtubule doublets 1 and 9 to ensure proper sperm movement
Year: 2023
Type: article
Abstract: The molecular mechanism underlying asymmetric axonemal complexes in sperm flagella is still largely unknown. Here, we showed that the knockout of the coiled-coil domain-containing 176 (CCDC176) in mice led to male infertility due to decreased sperm motility. Ccdc176 knockout specifically destabilized microtubule doublets (MTDs) 1 and 9 during sperm maturation in the corpus epididymis. Single-sperm immunofluorescence showed that most CCDC176 was distributed along the axoneme, and further super-resolution imaging revealed that CCDC176 is asymmetrically localized in the sperm axoneme. CCDC176 could cooperate with microtubule and radial spoke proteins to stabilize MTDs 1 and 9, and its knockout results in the destabilization of some proteins in sperm flagella. Furthermore, as predicted by the sperm multibody dynamics (MBD) model, we found that MTDs 1 and 9 jutted out from the sperm flagellum annulus region in Ccdc176 −/− spermatozoa, and these flagellar defects alter sperm flagellar beat patterns and swimming paths, potentially owing to the reduction and disequilibration of bending torque on the central pair. These results demonstrate that CCDC176 specifically stabilizes MTDs 1 and 9 in the sperm flagellum to ensure proper sperm movement for fertilization.
Source: Current Biology
Institutions: Chinese Academy of Sciences, Guangzhou Women and Children Medical Center, Institute of Zoology, State Key Laboratory of Stem Cell and Reproductive Biology, Guangzhou Medical University, Wenzhou Institute, University of Chinese Academy of Sciences, Institute of Biophysics, University of Chinese Academy of Sciences, Shandong University, Hospital for Reproductive Medicine Affiliated to Shandong University, Nanjing Medical University, Center for Excellence in Molecular Cell Science, Wuhan University, Zhejiang University
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $6,830
OpenAlex ID: W4385250131