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 in vivo. After RA treatment in infertile cryptorchid testis in vivo, 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 in vitro, 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 in vivo. 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.

隐睾引起的成人不育是男性不育的特发性原因的常见组成部分。视黄酸 (RA) 对精子发生过程具有重要影响。在这里，我们发现新生隐睾不育大鼠补充 RA 后，c-Kit、Stra8 和 Sycp3 的表达可以通过激活视黄酸受体 α (RARα) 上调。我们还证明，隐睾中 PI3K、p-Akt/pan-Akt 和 p-mTOR/mTOR 的蛋白质表达高于正常睾丸，并且可以在体内被 RA 抑制。体内RA 治疗不育隐睾睾丸后, 自噬蛋白 LC3 和 Beclin1 的水平升高，而 P62 的水平降低。生物素示踪剂表明，RA 给药后隐睾大鼠血液睾丸屏障 (BTB) 的通透性降低。此外，在体外睾丸培养中，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加和减少，这与正常睾丸相一致。体内隐睾. 此外，适当浓度的 RA 治疗可以抑制 PI3K-Akt-mTOR 信号通路并改善自噬通路。结果证实，RA可以通过RARα抑制PI3K-Akt-mTOR信号通路来恢复BTB功能并驱动精原细胞分化中的关键蛋白水平。