Expression And Significance Of MiR-34c And Nanos2 In Cryptorchidism

Objective Cryptorchidism as a genitourinary malformation is one of the common causes of male infertility.Highly conserved mi R-34 c plays an important role in spermatogenesis,Nanos2 maintains spermatogonial cell pool stability by inhibiting spermatogonial cell differentiation.However,the expression of micro RNA-34 c and Nanos2 in cryptorchidism remain unclear.In the present study,we explored the expression of mi R-34 c and Nanos2 in cryptorchidism and their association with spermatogenesis failure in cryptorchidism patients.Methods The testicular tissues of six cryptorchidism patients and six obstructive azoospermia patients were collected,the relative expression of mi R-34 c was detected by quantitative RT-PCR in testicular tissues of cryptorchidism patients.We used bioinformatics tools Target Scan and mi RDB to predict the target of mi R-34 c,and examined the effects of mi R-34 c overexpression and knockdown on Nanos2 expression in GC-1 mouse spermatogonial cell.We established a mouse model of cryptorchidism to detect the expression of mi R-34 c and Nanos2 in the model.In addition,we counted the number of Plzf-positive spermatogonia to investigate the effect of abnormal expression of mi R-34 c and Nanos2 on the stability of spermatogonial cell pool in cryptorchid mouse.Results In the present study,we found that cryptorchidism can seriously damage spermatogenesis in the testis,and the expression of mi R-34 c in testicular tissue of cryptorchidism patients was significantly down-regulated compared with obstructive azoospermia.Bioinformatics predictions suggest that Nanos2 may be one of the targets of mi R-34 c,and the results of GC-1 mouse spermatogonial cell showed that mi R-34 c could regulate the expression of Nanos2 and the expression level of both was negatively correlated.In mouse model of cryptorchidism,the expression level of mi R-34 c was significantly down-regulated and that of Nanos2 was significantly up-regulated,there was a negative correlation between the expression level of mi R-34 c and Nanos2 in this model.In addition,the number of Plzf-positive spermatogonia in mouse model of cryptorchidism increased significantly on the 14 th day after operation,and the stability of spermatogonia pool was changed.Conclusion Cryptorchidism can seriously damage spermatogenesis in the testis and the expression of mi R-34 c in testicular tissue of cryptorchidism patients was significantly down-regulated.Abnormal expression of the mi R-34c/Nanos2 pathway disturbs the balance between self-renewal and differentiation of spermatogonial stem cells and destroys the stability of spermatogonial cell pool,eventually damaging the spermatogenesis of cryptorchid testes.Our study provides new insight for the pathogenesis of spermatogenesis failure in cryptorchidism patients and we propose that mi R-34 c may serve as a novel target for treatment of male infertility caused by cryptorchidism.