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Published on: December 12, 2011
The cilia and flagella associated protein CFAP52 orchestrated with CFAP45 is required for sperm motility in mice
Bingbing Wu1, Rachel Li2, Shuang Ma1
1Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; University of the Chinese Academy of Sciences, Beijing, China.
Abstract:
Asthenozoospermia characterized by decreased sperm motility is a major cause of male infertility, but the majority of the etiology remains unknown. Here, we showed that the cilia and flagella associated protein 52 (Cfap52) gene was predominantly expressed in testis and its deletion in a Cfap52 knockout mouse model resulted in decreased sperm motility and male infertility. Cfap52 knockout also led to the disorganization of the midpiece-principal piece junction of the sperm tail but had no effect on the axoneme ultrastructure in spermatozoa. Furthermore, we found that CFAP52 interacted with the cilia and flagella associated protein 45 (CFAP45) and knockout of Cfap52 decreased the expression level of CFAP45 in sperm flagellum, which further disrupted the microtubule sliding produced by dynein ATPase. Together, our studies demonstrate that CFAP52 plays an essential role in sperm motility by interacting with CFAP45 in sperm flagellum, providing insights into the potential pathogenesis of the infertility of the human CFAP52 mutations.
Insights
Cilia and flagella associated protein 52 (Cfap52) is crucial for sperm motility and male fertility. Its absence in knockout mice caused infertility by disrupting sperm tail structure and CFAP45 interaction.
Area of Science:
- Reproductive Biology
- Molecular Biology
- Genetics
Background:
- Asthenozoospermia, characterized by reduced sperm motility, is a significant cause of male infertility with largely unknown etiology.
- Sperm motility is essential for natural fertilization.
Purpose of the Study:
- To investigate the role of cilia and flagella associated protein 52 (Cfap52) in sperm function and male fertility.
- To elucidate the molecular mechanisms underlying Cfap52's contribution to sperm motility.
Main Methods:
- Generation and analysis of a Cfap52 knockout mouse model.
- Assessment of sperm motility, sperm tail ultrastructure, and protein interactions within the sperm flagellum.
- Quantitative analysis of CFAP45 expression in wild-type and knockout sperm.
Main Results:
- Cfap52 is predominantly expressed in the testis.
- Cfap52 knockout mice exhibited decreased sperm motility and male infertility.
- Sperm from knockout mice showed disorganization at the midpiece-principal piece junction but intact axoneme ultrastructure.
- CFAP52 interacts with CFAP45, and its absence reduces CFAP45 levels in the sperm flagellum, impairing dynein-driven microtubule sliding.
Conclusions:
- CFAP52 is essential for maintaining sperm motility and male fertility.
- CFAP52 regulates sperm motility through interaction with CFAP45, impacting flagellar function.
- These findings provide insights into the pathogenesis of male infertility associated with human CFAP52 mutations.
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