CCDC181 is required for sperm flagellum biogenesis and male fertility in mice.

IF 4 1区 生物学 Q1 ZOOLOGY Zoological Research Pub Date : 2024-09-18 DOI:10.24272/j.issn.2095-8137.2024.075
Xiang-Jun Zhang, Xiao-Ning Hou, Jian-Teng Zhou, Bao-Lu Shi, Jing-Wei Ye, Meng-Lei Yang, Xiao-Hua Jiang, Bo Xu, Li-Min Wu, Qing-Hua Shi
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Abstract

The structural integrity of the sperm flagellum is essential for proper sperm function. Flagellar defects can result in male infertility, yet the precise mechanisms underlying this relationship are not fully understood. CCDC181, a coiled-coil domain-containing protein, is known to localize on sperm flagella and at the basal regions of motile cilia. Despite this knowledge, the specific functions of CCDC181 in flagellum biogenesis remain unclear. In this study, Ccdc181 knockout mice were generated. The absence of CCDC181 led to defective sperm head shaping and flagellum formation. Furthermore, the Ccdc181 knockout mice exhibited extremely low sperm counts, grossly aberrant sperm morphologies, markedly diminished sperm motility, and typical multiple morphological abnormalities of the flagella (MMAF). Additionally, an interaction between CCDC181 and the MMAF-related protein LRRC46 was identified, with CCDC181 regulating the localization of LRRC46 within sperm flagella. These findings suggest that CCDC181 plays a crucial role in both manchette formation and sperm flagellum biogenesis.

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CCDC181 是小鼠精子鞭毛生物发生和雄性生育能力的必要条件。
精子鞭毛结构的完整性对精子的正常功能至关重要。鞭毛缺陷可导致男性不育,但这种关系的确切机制尚不完全清楚。众所周知,CCDC181 是一种含线圈结构域的蛋白质,定位于精子鞭毛和运动纤毛的基部区域。尽管如此,CCDC181 在鞭毛生物发生过程中的具体功能仍不清楚。本研究生成了 Ccdc181 基因敲除小鼠。CCDC181 的缺失导致精子头部塑形和鞭毛形成缺陷。此外,Ccdc181 基因敲除小鼠表现出极低的精子数量、严重异常的精子形态、明显减弱的精子活力以及典型的鞭毛多重形态异常(MMAF)。此外,还发现了 CCDC181 与 MMAF 相关蛋白 LRRC46 之间的相互作用,CCDC181 可调节 LRRC46 在精子鞭毛内的定位。这些研究结果表明,CCDC181 在芒棘形成和精子鞭毛生物发生过程中都起着至关重要的作用。
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来源期刊
Zoological Research
Zoological Research Medicine-General Medicine
CiteScore
7.60
自引率
10.20%
发文量
1937
审稿时长
8 weeks
期刊介绍: Established in 1980, Zoological Research (ZR) is a bimonthly publication produced by Kunming Institute of Zoology, the Chinese Academy of Sciences, and the China Zoological Society. It publishes peer-reviewed original research article/review/report/note/letter to the editor/editorial in English on Primates and Animal Models, Conservation and Utilization of Animal Resources, and Animal Diversity and Evolution.
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