Autophagy maintains the homeostatic environment in the male reproductive accessory organs playing a key role in fertility
Autophagy maintains the homeostatic environment in the male reproductive accessory organs playing a key role in fertility
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DOI：
10.1101/2023.07.21.549845
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发表时间：
2023-07
期刊：
影响因子：
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通讯作者：
A. Jaulim;Liam D. Cassidy;A. Young;A. Chan;A. Warren;A. Taylor;W. Arlt;Guocheng Lan;M. Blayney;Olivia Davidson;C. L. Barratt;S. Pacey;M. Narita
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文献类型：
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作者：
A. Jaulim;Liam D. Cassidy;A. Young;A. Chan;A. Warren;A. Taylor;W. Arlt;Guocheng Lan;M. Blayney;Olivia Davidson;C. L. Barratt;S. Pacey;M. Narita
自噬与男性生育能力有关，但其在睾丸后器官中的具体作用尚不清楚。在这里，我们在表达强力霉素诱导的抗Atg5 (Atg5i) RNAi的小鼠中研究了这一点。Atg5i小鼠的全身自噬抑制导致雄性副性器官在形态和功能上的丧失，导致雄性不育。然而，睾丸在很大程度上受到了保护，可能是由于强力霉素通过血睾丸屏障的渗透性有限。有趣的是，Atg5i小鼠停用强力霉素后自噬的恢复导致附属器官表型的显著恢复。该模型提供了一个独特的机会来剖析自噬在睾丸前和睾丸后的作用，突出了自噬对男性生育能力的非自主性影响。
Autophagy has been implicated in male fertility but its specific role in the post-testicular organs remains unclear. Here, we investigate this in mice expressing a doxycycline-inducible RNAi against Atg5 (Atg5i). Systemic autophagy inhibition in Atg5i mice resulted in the morphological and functional abrogation of the male accessory sex organs, leading to male subfertility. However, the testis was largely protected, likely due to the limited permeability of doxycycline through the blood-testis barrier. Interestingly, restoration of autophagy by doxycycline withdrawal in Atg5i mice led to substantial recovery of the phenotype in the accessory organs. This model offers a unique opportunity to dissect the pre- and post-testicular roles of autophagy, highlighting the non-autonomous impact of autophagy on male fertility.