CEP164 is essential for efferent duct multiciliogenesis and male fertility.
CEP164 is essential for efferent duct multiciliogenesis and male fertility.
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DOI：
10.1530/rep-21-0042
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发表时间：
2021-07-08
期刊：
影响因子：
--
通讯作者：
Takemaru KI
中科院分区：
文献类型：
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作者：
Hoque M;Chen D;Hess RA;Li FQ;Takemaru KI
纤毛是进化上保守的基于微管的结构，执行不同的生物学功能。纤毛组装在基体上，并通过远端附属物锚定在质膜上。在男性生殖道中，传出导管（ED）中的多纤毛以鞭子状运动，以防止精子凝集。以前，我们证明了远端附属蛋白CEP 164招募Chibby 1（Cby 1）到基体，以促进基体对接和纤毛发生。在多纤毛细胞（MCCs）中缺乏CEP 164的小鼠（FoxJ 1-Cre; CEP 164 fl/fl）显示气管、输卵管和室管膜中的多纤毛的显著损失。此外，我们观察到雄性不育，然而，CEP 164在雄性育性中的确切作用仍然未知。在这里，我们报告FoxJ 1-Cre; CEP 164 fl/fl小鼠的曲细精管和睾丸网表现出大幅扩张，表明ED中多毛功能失调。我们发现，虽然FoxJ 1阳性的未成熟细胞存在，但在FoxJ 1-Cre; CEP 164 fl/fl小鼠的ED中几乎检测不到多纤毛。在FoxJ 1-Cre; CEP 164 fl/fl小鼠的生精小管和ED的管腔中通常可观察到精子聚集和凝集。在FoxJ 1-Cre中;在CEP 164 fl/fl小鼠中，Cby 1和过渡区标记物NPHP 1的顶端定位严重减少，表明基底体对接缺陷。ED的TEM分析进一步证实了MCC细胞质中的基体积累。总的来说，我们得出结论，FoxJ 1-Cre; CEP 164 fl/fl小鼠的雄性不育是由于精子凝集和ED阻塞，由于损失的多纤毛。因此，我们的研究揭示了远端附件蛋白CEP 164在男性生育中的重要作用。
Cilia are evolutionarily conserved microtubule-based structures that perform diverse biological functions. Cilia are assembled on basal bodies and anchored to the plasma membrane via distal appendages. In the male reproductive tract, multicilia in efferent ducts (EDs) move in a whip-like motion to prevent sperm agglutination. Previously, we demonstrated that the distal appendage protein CEP164 recruits Chibby1 (Cby1) to basal bodies to facilitate basal body docking and ciliogenesis. Mice lacking CEP164 in multiciliated cells (MCCs) (FoxJ1-Cre;CEP164fl/fl) show a significant loss of multicilia in the trachea, oviduct, and ependyma. In addition, we observed male sterility, however, the precise role of CEP164 in male fertility remained unknown. Here, we report that the seminiferous tubules and rete testis of FoxJ1-Cre;CEP164fl/fl mice exhibit substantial dilation, indicative of dysfunctional multicilia in the EDs. We found that multicilia were hardly detectable in the EDs of FoxJ1-Cre;CEP164fl/fl mice although FoxJ1-positive immature cells were present. Sperm aggregation and agglutination were commonly noticeable in the lumen of the seminiferous tubules and EDs of FoxJ1-Cre;CEP164fl/fl mice. In FoxJ1-Cre;CEP164fl/fl mice, the apical localization of Cby1 and the transition zone marker NPHP1 was severely diminished, suggesting basal body docking defects. TEM analysis of EDs further confirmed basal body accumulation in the cytoplasm of MCCs. Collectively, we conclude that male infertility in FoxJ1-Cre;CEP164fl/fl mice is caused by sperm agglutination and obstruction of EDs due to loss of multicilia. Our study, therefore, unravels an essential role of the distal appendage protein CEP164 in male fertility.