CCDC181 对于精子鞭毛的发生和雄性小鼠的生育能力是必需的。

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

机构信息

Division of Reproduction and Genetics, First Affiliated Hospital of University of Science and Technology of China (USTC), Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei, Anhui 230001, China.

出版信息

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

DOI:10.24272/j.issn.2095-8137.2024.075

PMID:39245650

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11491787/

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, knockout mice were generated. The absence of CCDC181 led to defective sperm head shaping and flagellum formation. Furthermore, the 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.

摘要

精子鞭毛的结构完整性对于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。已知卷曲螺旋域蛋白 181 (CCDC181) 定位于精子鞭毛和运动纤毛的基底区域。尽管有这些知识，但 CCDC181 在鞭毛发生中的具体功能仍不清楚。在这项研究中，生成了 CCDC181 基因敲除小鼠。CCDC181 的缺失导致精子头部形状和鞭毛形成缺陷。此外，CCDC181 基因敲除小鼠的精子计数极低，精子形态明显异常，运动能力显著降低，鞭毛具有典型的多种形态异常（MMAF）。此外，还鉴定到 CCDC181 与与 MMAF 相关的蛋白 LRRC46 之间存在相互作用，CCDC181 调节 LRRC46 在精子鞭毛中的定位。这些发现表明 CCDC181 在顶体囊形成和精子鞭毛发生中都起着关键作用。