气候变化领域集成服务门户(CCPortal): Absence of murine CFAP61 causes male infertility due to multiple morphological abnormalities of the flagella

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DOI	10.1016/j.scib.2020.01.023
	Absence of murine CFAP61 causes male infertility due to multiple morphological abnormalities of the flagella
	Huang T.; Yin Y.; Liu C.; Li M.; Yu X.; Wang X.; Zhang H.; Muhammad T.; Gao F.; Li W.; Chen Z.-J.; Liu H.; Ma J.
发表日期	2020
ISSN	20959273
起始页码	854
结束页码	864
卷号	65 期号:10
英文摘要	Impaired flagellar development and impaired motility of sperm is a cause of infertility in males. Several genes, including those of the AKAP, CCDC, CFAP, and DNAH families, among others, are involved in the “multiple morphological abnormalities of the flagella” (MMAF) phenotype; these are the most common causes of male infertility. The Cilia-and flagella-associated protein (CFAP) family includes six members reported to cause MMAF phenotypes: CFAP43, CFAP44, CFAP69, CFAP65, CFAP70, and CFAP251. Here, we found that cilia-and flagella-associated protein 61 (Cfap61) is highly expressed specifically in murine testes and show that the Cfap61-knockout male mice demonstrate MMAF phenotype, including sperm with short, coiled, and irregular flagella. Deletion of Cfap61 resulted in severe morphological and behavior abnormalities in sperm, reduced total sperm counts, impaired sperm motility, and led to male infertility. Notably, absence of Cfap61 impaired sperm flagella ultrastructural abnormalities on account of numerous distortions in multiple flagellum components. Immunostaining experiments in wild-type mice and healthy adult humans indicated that Cfap61 is initially localized at the neck of sperm, where it potentially functions in flagellum formation, and is later localized to the midpiece of the sperm. Thus, our study provides compelling evidence that dysregulation of Cfap61 affects sperm flagellum development and induces male infertility in mice. Further investigations of the CFAP61 gene in humans alongside clinical evidence showing MMAF phenotype in humans should contribute to our understanding of developmental processes underlying sperm flagellum formation and the pathogenic mechanisms that cause male infertility. © 2020 Science China Press
关键词	Cfap61 Flagellum development Male infertility Multiple morphological abnormalities of the flagella (MMAF)
英文关键词	Genes; Proteins; Cfap61; Flagellum development; Immunostaining; Male infertility; Pathogenic mechanisms; Sperm counts; Sperm motility; The multiple morphological abnormalities of the flagella (MMAF); Mammals
语种	英语
来源期刊	Science Bulletin
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/207068
作者单位	Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, 250012, China; Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, 250012, China; Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, 250012, China; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China; Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200000, China; Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, 200000, China
推荐引用方式 GB/T 7714	Huang T.,Yin Y.,Liu C.,et al. Absence of murine CFAP61 causes male infertility due to multiple morphological abnormalities of the flagella[J],2020,65(10).
APA	Huang T..,Yin Y..,Liu C..,Li M..,Yu X..,...&Ma J..(2020).Absence of murine CFAP61 causes male infertility due to multiple morphological abnormalities of the flagella.Science Bulletin,65(10).
MLA	Huang T.,et al."Absence of murine CFAP61 causes male infertility due to multiple morphological abnormalities of the flagella".Science Bulletin 65.10(2020).