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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
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 rece...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Chongqing Medical University
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293722/ https://www.ncbi.nlm.nih.gov/pubmed/35873030 http://dx.doi.org/10.1016/j.gendis.2021.03.006 |
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author | Long, Chunlan Zhou, Yu Shen, Lianju Yu, Yihang Hu, Dong Liu, Xing Lin, Tao He, Dawei Xu, Tao Zhang, Deying Zhu, Jing Wei, Guanghui |
author_facet | Long, Chunlan Zhou, Yu Shen, Lianju Yu, Yihang Hu, Dong Liu, Xing Lin, Tao He, Dawei Xu, Tao Zhang, Deying Zhu, Jing Wei, Guanghui |
author_sort | Long, Chunlan |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9293722 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Chongqing Medical University |
record_format | MEDLINE/PubMed |
spelling | pubmed-92937222022-07-21 Retinoic acid can improve autophagy through depression of the PI3K-Akt-mTOR signaling pathway via RARα to restore spermatogenesis in cryptorchid infertile rats Long, Chunlan Zhou, Yu Shen, Lianju Yu, Yihang Hu, Dong Liu, Xing Lin, Tao He, Dawei Xu, Tao Zhang, Deying Zhu, Jing Wei, Guanghui Genes Dis Full Length Article 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. Chongqing Medical University 2021-04-02 /pmc/articles/PMC9293722/ /pubmed/35873030 http://dx.doi.org/10.1016/j.gendis.2021.03.006 Text en © 2021 Chongqing Medical University. Production and hosting by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Full Length Article Long, Chunlan Zhou, Yu Shen, Lianju Yu, Yihang Hu, Dong Liu, Xing Lin, Tao He, Dawei Xu, Tao Zhang, Deying Zhu, Jing Wei, Guanghui Retinoic acid can improve autophagy through depression of the PI3K-Akt-mTOR signaling pathway via RARα to restore spermatogenesis in cryptorchid infertile rats |
title | Retinoic acid can improve autophagy through depression of the PI3K-Akt-mTOR signaling pathway via RARα to restore spermatogenesis in cryptorchid infertile rats |
title_full | Retinoic acid can improve autophagy through depression of the PI3K-Akt-mTOR signaling pathway via RARα to restore spermatogenesis in cryptorchid infertile rats |
title_fullStr | Retinoic acid can improve autophagy through depression of the PI3K-Akt-mTOR signaling pathway via RARα to restore spermatogenesis in cryptorchid infertile rats |
title_full_unstemmed | Retinoic acid can improve autophagy through depression of the PI3K-Akt-mTOR signaling pathway via RARα to restore spermatogenesis in cryptorchid infertile rats |
title_short | Retinoic acid can improve autophagy through depression of the PI3K-Akt-mTOR signaling pathway via RARα to restore spermatogenesis in cryptorchid infertile rats |
title_sort | retinoic acid can improve autophagy through depression of the pi3k-akt-mtor signaling pathway via rarα to restore spermatogenesis in cryptorchid infertile rats |
topic | Full Length Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293722/ https://www.ncbi.nlm.nih.gov/pubmed/35873030 http://dx.doi.org/10.1016/j.gendis.2021.03.006 |
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