Retinoic acid can improve autophagy through depression of the PI3K-Akt-mTOR signaling pathway via RARαto restore spermatogenesis in cryptorchid infertile rats
作者机构：Chongqing Key Laboratory of Children Urogenital Development and Tissue EngineeringMinistry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Key Laboratory of PediatricsChongqing 400014PR China Department of UrologyChildren’s Hospital of Chongqing Medical UniversityChongqing 400014PR China Bio-manufacturing CenterDepartment of Mechanical EngineeringTsinghua UniversityBeijing 100084PR China
出 版 物：《Genes & Diseases》 (基因与疾病（英文）)
年 卷 期：2022年第9卷第5期
页 面：1368-1377页
核心收录：
学科分类：0710[理学-生物学] 0831[工学-生物医学工程（可授工学、理学、医学学位）] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 0703[理学-化学] 10[医学]
基 金：supported by the National Natural Science Foundation of China(No.81771566),the Science and Technology Research Program of Chongqing Municipal Education Commission,China(No.KJQN201900444) the Highlevel Medical Reserved Personnel Training Project of Chongqing,China(No.230) the Chongqing Science and Technology Commission,China(No.cstc2018jcyjAX0193)。
主 题：Cryptorchidism Male infertility Retinoic acid Spermatogenesis Testis
摘 要：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 receptorα(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 RARαwith AR7(an RARαantagonist)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.
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