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Ccdc38 is required for sperm flagellum biogenesis and male fertility in mouse

Ruidan Zhang, Bingbing Wu, Chao Liu, Xiuge Wang, Liying Wang, Sai Xiao, Yinghong Chen, Huafang Wei, Fei Gao, Li Yuan, View ORCID ProfileWei Li
doi: https://doi.org/10.1101/2022.01.10.475757
Ruidan Zhang
1State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
2University of the Chinese Academy of Sciences, Beijing 100049, China
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Bingbing Wu
1State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
2University of the Chinese Academy of Sciences, Beijing 100049, China
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Chao Liu
1State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
3Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 510623 Guangzhou, China
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Xiuge Wang
1State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
2University of the Chinese Academy of Sciences, Beijing 100049, China
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Liying Wang
1State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
3Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 510623 Guangzhou, China
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Sai Xiao
1State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
2University of the Chinese Academy of Sciences, Beijing 100049, China
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Yinghong Chen
1State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
2University of the Chinese Academy of Sciences, Beijing 100049, China
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Huafang Wei
1State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
3Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 510623 Guangzhou, China
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Fei Gao
1State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
2University of the Chinese Academy of Sciences, Beijing 100049, China
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  • For correspondence: leways@ioz.ac.cn yuanli@ucas.ac.cn gaof@ioz.ac.cn
Li Yuan
4Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China
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  • For correspondence: leways@ioz.ac.cn yuanli@ucas.ac.cn gaof@ioz.ac.cn
Wei Li
1State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
3Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 510623 Guangzhou, China
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  • ORCID record for Wei Li
  • For correspondence: leways@ioz.ac.cn yuanli@ucas.ac.cn gaof@ioz.ac.cn
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Abstract

Sperm flagellum is essential for male fertility, defects in flagellum biogenesis are associated with male infertility. Deficiency of CCDC42 is associated with malformation of the mouse sperm flagella. Here, we find that the testis-specific expressed protein CCDC38 (coiled-coil domain containing 38) interacts with CCDC42 and localizes on manchette and sperm tail during spermiogenesis. Inactivation of CCDC38 in male mice results in distorted manchette, multiple morphological abnormalities of the flagella (MMAF) of spermatozoa, and eventually male sterility. Furthermore, we find that CCDC38 interacts with intra-flagellar transport protein 88 (IFT88) as well as the outer dense fibrous 2 (ODF2), and its depletion reduces the transportation of ODF2 to flagellum. Altogether, our results uncover the essential role of CCDC38 during sperm flagellum biogenesis, and suggesting the defects of these genes might be associated with male infertility in human being.

Summary statement We demonstrated that CCDC38, localizes on manchette and sperm tail, is crucial for male fertility.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted January 11, 2022.
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Ccdc38 is required for sperm flagellum biogenesis and male fertility in mouse
Ruidan Zhang, Bingbing Wu, Chao Liu, Xiuge Wang, Liying Wang, Sai Xiao, Yinghong Chen, Huafang Wei, Fei Gao, Li Yuan, Wei Li
bioRxiv 2022.01.10.475757; doi: https://doi.org/10.1101/2022.01.10.475757
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Ccdc38 is required for sperm flagellum biogenesis and male fertility in mouse
Ruidan Zhang, Bingbing Wu, Chao Liu, Xiuge Wang, Liying Wang, Sai Xiao, Yinghong Chen, Huafang Wei, Fei Gao, Li Yuan, Wei Li
bioRxiv 2022.01.10.475757; doi: https://doi.org/10.1101/2022.01.10.475757

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