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,St...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.展开更多
This study aims to determine key genes and pathways that could play important roles in the spermatogenic process of patients with cryptorchidism.The gene expression profile data of GSE25518 was obtained from the Gene ...This study aims to determine key genes and pathways that could play important roles in the spermatogenic process of patients with cryptorchidism.The gene expression profile data of GSE25518 was obtained from the Gene Expression Omnibus(GEO)database.Microarray data were analyzed using BRB-Array Tools to identify differentially expressed genes(DEGs)between high azoospermia risk(HAZR)patients and controls.In addition,other analytical methods were deployed,including hierarchical clustering analysis,class comparison between patients with HAZR and the normal control group,gene ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis,and the construction of a proteineprotein interaction(PPI)network.In total,1015 upregulated genes and 1650 downregulated genes were identified.GO and KEGG analysis revealed enrichment in terms of changes in the endoplasmic reticulum cellular component and the endoplasmic reticulum protein synthetic process in the HAZR group.Furthermore,the arachidonic acid pathway and mTOR pathway were also identified as important pathways,while RICTOR and GPX8 were indentified as key genes involved in the spermatogenic process of patients with cryptorchidism.In present study,we found that changes in the synthesis of endoplasmic reticulum proteins,arachidonic acid and the mTOR pathway are important in the incidence and spermatogenic process of cryptorchidism.GPX8 and RICTOR were also identified as key genes associated with cryptorchidism.Collectively,these data may provide novel clues with which to explore the precise etiology and mechanism underlying cryptorchidism and cryptorchidism-induced human infertility.展开更多
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.[2018]230)the Chongqing Science and Technology Commission,China(No.cstc2018jcyjAX0193)。
文摘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.
基金The present study was financially supported by National Natural Science Foundation of China(Grant No.81771566)Entrepreneurship and Innovation Support Program for Returned Overseas Chinese Scholars,Chongqing(Grant No.cx2017015)Research and Innovation Project of Chongqing Graduate Students(Grant No.CYS17165).
文摘This study aims to determine key genes and pathways that could play important roles in the spermatogenic process of patients with cryptorchidism.The gene expression profile data of GSE25518 was obtained from the Gene Expression Omnibus(GEO)database.Microarray data were analyzed using BRB-Array Tools to identify differentially expressed genes(DEGs)between high azoospermia risk(HAZR)patients and controls.In addition,other analytical methods were deployed,including hierarchical clustering analysis,class comparison between patients with HAZR and the normal control group,gene ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis,and the construction of a proteineprotein interaction(PPI)network.In total,1015 upregulated genes and 1650 downregulated genes were identified.GO and KEGG analysis revealed enrichment in terms of changes in the endoplasmic reticulum cellular component and the endoplasmic reticulum protein synthetic process in the HAZR group.Furthermore,the arachidonic acid pathway and mTOR pathway were also identified as important pathways,while RICTOR and GPX8 were indentified as key genes involved in the spermatogenic process of patients with cryptorchidism.In present study,we found that changes in the synthesis of endoplasmic reticulum proteins,arachidonic acid and the mTOR pathway are important in the incidence and spermatogenic process of cryptorchidism.GPX8 and RICTOR were also identified as key genes associated with cryptorchidism.Collectively,these data may provide novel clues with which to explore the precise etiology and mechanism underlying cryptorchidism and cryptorchidism-induced human infertility.