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Volume 35, No 8, Aug 2025

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 35 Issue 8, August 2025: 551-567   |  Open Access

ORIGINAL ARTICLES

In situ structure of the mouse sperm central apparatus reveals mechanistic insights into asthenozoospermia

Yun Zhu1,†,* , Tingting Lin2,3,† , 1,4,* , Linhua Tai1,4 , Lianwan Chen1 , Jing Ma2,3 , Guoning Huang2,3 , Yi Lu5 , Zhiyong Zhang5,6 , Binbin Wang7,8,9 , Suren Chen10,* , Fei Sun1,4,11,12,*

1National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
2Chongqing Key Laboratory of Human Embryo Engineering and Precision Medicine, Center for Reproductive Medicine, Women and Children’s Hospital of Chongqing Medical University, Chongqing, China
3Chongqing Clinical Research Center for Reproductive Medicine, Chongqing Health Center for Women and Children, Chongqing, China
4School of Life Sciences, University of Chinese Academy of Sciences, Beijing, China
5Department of Physics, University of Science and Technology of China, Hefei, Anhui, China
6MOE Key Laboratory for Cellular Dynamics, University of Science and Technology of China, Hefei, Anhui, China
7Graduate School, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
8Department of Urology, Peking Union Medical College Hospital, Beijing, China
9Center for Genetics, National Research Institute of Family Planning, Beijing, China
10Education Key Laboratory of Cell Proliferation and Regulation Biology, College of Life Sciences, Beijing Normal University, Beijing, China
11Center for Biological Imaging, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
12Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, China
†These authors contributed equally: Yun Zhu, Tingting Lin
Correspondence: Yun Zhu(zhuyun@ibp.ac.cn)()Suren Chen(chensr@bnu.edu.cn)Fei Sun(feisun@ibp.ac.cn)

The central apparatus (CA) within the sperm axoneme is vital for sperm motility, yet its molecular architecture and functional mechanisms remain incompletely understood. Combining cryo-electron tomography and AlphaFold2, we resolved the in-cell structure of mouse sperm CA at a subnanometer resolution and built a near-complete atomic model. Our analysis identified 39 CA-associated proteins, including eight previously unreported components. By presenting the full-length structures of CFAP47 and HYDIN, we elucidate their molecular roles in tethering the C1 and C2 microtubules within the CA. Specifically, HYDIN forms a semicircular chain that encircles C1 and C2, with its N-terminal half driving the C1–C2 connection and its C-terminal half providing axial support in C2. CFAP47, the core structural component of the bridge, binds C1 through its N-terminal domains, interacts with HYDIN via its central CFAP47-ring, and anchors to C2 through its C-terminal region. The significantly reduced sperm motility and impaired CA structure observed in Cfap47-knockout mice confirmed the important role of CFAP47. Furthermore, genetic analysis of infertile Chinese men with asthenozoospermia identified previously unreported mutations in the CFAP47. The CA structural model elucidates the pathogenic mechanisms of these mutations, establishing a direct link between CFAP47 dysfunction and impaired sperm motility. Therefore, our study provides mechanistic insights into CA-related fertility disorders.


https://doi.org/10.1038/s41422-025-01135-2

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