| In recent years, infertility is a major health problem that affects 10–15% of couples and ~50% of infertility cases are attributed to the male partner. NOA, the etiology affecting approximately 60-75% of azoospermic men, results from defective sperm production, obstruction or physical blockage of the reproductive tract, inflammation or immunological dysfunction or sexual disorders. In 10–15% of cases, numeric and structural abnormalities of chromosomes and Y chromosome deletions that encompass critical spermatogenesis genes are detected; in the remaining cases, the cause of infertility is unknown Although with assisted reproductive technologies such as single sperm intracytoplasmic injection(ICSI) development, for the infertile patients provides can procreate, but ICSI bypasses sperm fertilization in the process of natural selection mechanism are pass on genetic defects to the next generation of risk. Therefore, it is important to understand the genetic basis of spermatogenesis, which is important to elucidate the etiology of idiopathic male infertility.Spermatogenesis is a complex developmental process in which undifferentiated spermatogonia are differentiated into spermatocytes and spermatids through two rounds of meiotic division and finally giving rise to mature spermatozoa(sperm). These processes involve many testis- or male germ cell-specific gene products that undergo strict developmental regulations. In the spermatogenesis and meiosis of haploid formation process, transcriptional activity is increased and translation is inhibited which is regulated by post-transcriptional,such as micro RNAs(mi RNAs). Testis specific protein 15(TEX15) is closely related to the process of meiosis and loss of TEX15 function in mice causes a failure in meiotic recombination which leads male infertility. Therefore, TEX15 is likely to play an important role in the occurrence of NOA patients, but the specific mechanism of TEX15 transcriptional and post transcriptional regulation is unknown. In this study, we found that the expression of TEX15 m RNA in NOA patients was significantly lower than in normal controls. Immunohistochemical results also confirmed that the TEX15 protein expression was significantly down regulated in spermatogonial cells of NOA patients. Using multiple databases, including Target Scan, Pic Tar, and mi Randa, one conserved mi R-183 target site in the TEX15 3’UTR was predicted. The results of luciferase reporter assay confirmed that TEX15 was the targer of mi R-183. Moreover, we observed that the expression of TEX15 m RNA was significantly promoted in the U2 OS cell transfected with mi R-183 inhibitor. In addition, the expression of mi R-183 in NOA patients was significantly increased compared with the control which was significant negative correlation with TEX15 expression. Ferthermore, we examined the expression of TEX15 and mi R-183 in different stages of mouse testis, including 8d,14 d,16d,18 d,25d,2m, which showed significant negative correlation. Our data indicated that mi R-183 suppresed the translation of TEX15 by binding to the TEX15 3’UTR which may directly results in meiotic chromosome synapsis, genetic recombination and DNA repair of double stranded obstacles, and ultimately leads to infertility.In this study, we demonstrate that mi R-183 regulates the process of spermatogenesis by targeting TEX15. Our study will provide a new understanding of the molecular mechanism of sperm defects. |
