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
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.
