Retinoic acid can improve autophagy through depression of the PI3K-Akt-mTOR signaling pathway via RARα to restore spermatogenesis in cryptorchid infertile rats

Chunlan Long; Yu Zhou; Lianju Shen; Yihang Yu; Dong Hu; Xing Liu; Tao Lin; Dawei He; Tao Xu; Deying Zhang; Jing Zhu; Guanghui Wei

doi:10.1016/j.gendis.2021.03.006

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Retinoic acid can improve autophagy through depression of the PI3K-Akt-mTOR signaling pathway via RARα to restore spermatogenesis in cryptorchid infertile rats

更新时间：2022-08-11

- Retinoic acid can improve autophagy through depression of the PI3K-Akt-mTOR signaling pathway via RARα to restore spermatogenesis in cryptorchid infertile rats
- Genes & Diseases Vol. 9, Issue 5, (2022)
- 作者机构：
  
  1. 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,PR China,400014
  2. Department of Urology, Children's Hospital of Chongqing Medical University,Chongqing,PR China,400014
  3. Bio-manufacturing Center, Department of Mechanical Engineering, Tsinghua University,Beijing,PR China,100084
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2021.03.006
  CLC：
- Published：2022，
  
  Published Online：1 September 2022，
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Chunlan Long, Yu Zhou, Lianju Shen, et al. Retinoic acid can improve autophagy through depression of the PI3K-Akt-mTOR signaling pathway via RARα to restore spermatogenesis in cryptorchid infertile rats. [J]. Genes & Diseases 9(5).(2022)
DOI：

Chunlan Long, Yu Zhou, Lianju Shen, et al. Retinoic acid can improve autophagy through depression of the PI3K-Akt-mTOR signaling pathway via RARα to restore spermatogenesis in cryptorchid infertile rats. [J]. Genes & Diseases 9(5).(2022) DOI： 10.1016/j.gendis.2021.03.006.

摘要

Abstract

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.

关键词

Keywords

CryptorchidismMale infertilityRetinoic acidSpermatogenesisTestis

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