Long Chunlan, Zhou Yu, Shen Lianju, Yu Yihang, Hu Dong, Liu Xing, Lin Tao, He Dawei, Xu Tao, Zhang Deying, Zhu Jing, Wei Guanghui
Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing 400014, PR China.
Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China.
Genes Dis. 2021 Apr 2;9(5):1368-1377. doi: 10.1016/j.gendis.2021.03.006. eCollection 2022 Sep.
Cryptorchidism-caused adult infertility is a common component of idiopathic reasons for male infertility. Retinoic acid (RA) has a vital effect on the spermatogenesis process. Here, we found that the expression of c-Kit, Stra8, and Sycp3 could be up-regulated via the activation of retinoic acid receptor α (RARα) after RA supplementation in neonatal cryptorchid infertile rats. We also demonstrated that the protein expression of PI3K, p-Akt/pan-Akt, and p-mTOR/mTOR was higher in cryptorchid than in normal testes, and could be suppressed with RA . After RA treatment in infertile cryptorchid testis , the levels of the autophagy proteins LC3 and Beclin1 increased and those of P62 decreased. Biotin tracer indicated that the permeability of blood-testis barrier (BTB) in cryptorchid rats decreased after RA administration. Additionally, after blocking the RARα with AR7 (an RARα antagonist) in testicle culture , we observed that compared with normal testes, the PI3K-Akt-mTOR signaling pathway and the autophagy pathway was increased and decreased, respectively, which were coincident with cryptorchisd testes . Additionally, the appropriate concentrations of RA treatment could depress the PI3K-Akt-mTOR signaling pathway and improve the autophagy pathway. The results confirmed that RA can rehabilitate BTB function and drive key protein levels in spermatogonial differentiation through depressing the PI3K-Akt-mTOR signaling pathway via RARα.
隐睾症导致的成年不育是男性不育特发性原因的常见组成部分。视黄酸（RA）在精子发生过程中具有至关重要的作用。在此，我们发现，在新生隐睾不育大鼠补充RA后，通过激活视黄酸受体α（RARα），c-Kit、Stra8和Sycp3的表达可上调。我们还证明，PI3K、p-Akt/pan-Akt和p-mTOR/mTOR的蛋白表达在隐睾中高于正常睾丸，且可被RA抑制。在不育隐睾睾丸中进行RA治疗后，自噬蛋白LC3和Beclin1的水平升高，而P62的水平降低。生物素示踪表明，给予RA后，隐睾大鼠血睾屏障（BTB）的通透性降低。此外，在睾丸培养中用AR7（一种RARα拮抗剂）阻断RARα后，我们观察到，与正常睾丸相比，PI3K-Akt-mTOR信号通路和自噬通路分别增强和减弱，这与隐睾睾丸的情况一致。此外，适当浓度的RA治疗可抑制PI3K-Akt-mTOR信号通路并改善自噬通路。结果证实，RA可通过RARα抑制PI3K-Akt-mTOR信号通路，恢复BTB功能并驱动精原细胞分化中的关键蛋白水平。
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