Arrdc4-dependent extracellular vesicle biogenesis is required for sperm maturation.
Arrdc4-dependent extracellular vesicle biogenesis is required for sperm maturation.
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精子成熟需要依赖于Arrdc4的胞外囊泡生物发生。
DOI：
10.1002/jev2.12113
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发表时间：
2021-06
影响因子：
16
通讯作者：
Kumar S
中科院分区：
文献类型：
--
作者：
Foot NJ;Gonzalez MB;Gembus K;Fonseka P;Sandow JJ;Nguyen TT;Tran D;Webb AI;Mathivanan S;Robker RL;Kumar S
细胞外囊泡（EV）是生殖系统细胞间通讯的重要参与者。值得注意的是，已经在男性生殖道中发现并表征了EV，然而，缺乏其在介导精子功能中的重要性的直接功能证据。我们之前已经证明，Arrdc 4，α-arrestin蛋白家族的成员，参与细胞外囊泡的生物发生和释放。在这里，我们表明Arrdc 4介导的细胞外囊泡生物合成是正常精子功能所必需的。来自Arrdc 4-/-小鼠的精子通过睾丸正常发育，但通过附睾未能获得足够的运动和受精能力，如运动力降低、顶体过早反应、透明质酸结合减少和双细胞胚胎产生所观察到的。我们发现Arrdc 4-/-附睾上皮细胞产生的细胞外囊泡显著减少，此外，用额外的囊泡补充Arrdc 4-/-精子抑制了顶体反应缺陷并恢复了透明质酸结合。这些结果表明，Arrdc 4是重要的适当的精子成熟，通过控制细胞外囊泡的生物发生。
Extracellular vesicles (EVs) are important players in cell to cell communication in reproductive systems. Notably, EVs have been found and characterized in the male reproductive tract, however, direct functional evidence for their importance in mediating sperm function is lacking. We have previously demonstrated that Arrdc4, a member of the α‐arrestin protein family, is involved in extracellular vesicle biogenesis and release. Here we show that Arrdc4‐mediated extracellular vesicle biogenesis is required for proper sperm function. Sperm from Arrdc4–/– mice develop normally through the testis but fail to acquire adequate motility and fertilization capabilities through the epididymis, as observed by reduced motility, premature acrosome reaction, reduction in zona pellucida binding and two‐cell embryo production. We found a significant reduction in extracellular vesicle production by Arrdc4–/‐ epididymal epithelial cells, and further, supplementation of Arrdc4–/– sperm with additional vesicles dampened the acrosome reaction defect and restored zona pellucida binding. These results indicate that Arrdc4 is important for proper sperm maturation through the control of extracellular vesicle biogenesis.