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. 2024 Sep 18;45(5):1061-1072.
doi: 10.24272/j.issn.2095-8137.2024.075.

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

Xiang-Jun Zhang  1 , Xiao-Ning Hou  1 , Jian-Teng Zhou  1 , Bao-Lu Shi  1 , Jing-Wei Ye  1 , Meng-Lei Yang  1 , Xiao-Hua Jiang  1 , Bo Xu  1 , Li-Min Wu  2 , Qing-Hua Shi  3
Affiliations

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

Xiang-Jun Zhang et al. Zool Res. .

Abstract
in English, Chinese

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.

鞭毛结构的完整性对于精子的正常功能至关重要，它的缺陷常导致男性不育，目前相关致病机制尚不明确。卷曲螺旋结构域蛋白CCDC181定位于精子鞭毛和动纤毛基底部，它在精子鞭毛发生中的具体功能研究尚是空白。为了研究CCDC181蛋白在精子发生中发挥的功能，我们构建了 Ccdc181基因敲除小鼠模型，发现CCDC181蛋白的缺失会导致精子头部塑形和鞭毛形成的缺陷。 Ccdc181基因敲除小鼠生殖表型具体表现为精子数量减少、精子形态畸形、精子运动能力丧失以及典型的鞭毛多发形态异常（MMAF）。此外，该研究还发现CCDC181蛋白与已报道的MMAF相关蛋白LRRC46存在相互作用，且CCDC181蛋白缺失后影响了LRRC46在精子鞭毛的定位。综上所述，该研究表明，CCDC181蛋白在精子领和精子鞭毛形成过程中都起着至关重要的作用。.

Keywords: CCDC181; Flagellum biogenesis; MMAF; Male infertility; Spermiogenesis.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Generation and reproduction of Ccdc181 knockout mice
Figure 2
Figure 2
CCDC181 deficiency causes a significant decrease in elongated spermatids
Figure 3
Figure 3
CCDC181 deficiency impairs manchette formation and sperm head shaping
Figure 4
Figure 4
CCDC181 deficiency results in typical multiple morphological abnormalities of flagella phenotype in male mice
Figure 5
Figure 5
LRRC46 interacts with CCDC181 and its localization along flagella is dependent on CCDC181
Figure 6
Figure 6
Schematic showing localization of CCDC181 protein
See this image and copyright information in PMC

References

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