期刊
BIOLOGY OF REPRODUCTION
卷 101, 期 1, 页码 50-62出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/biolre/ioz062
关键词
CFTR; spermatogenesis; miR-15b; CDC25A
资金
- National Nature Science fund of China [81370747]
- National Key Research and Development Program of China [SQ2018YFC1003603]
MicroRNAs (miRNAs) have recently been shown to be important for spermatogenesis; both DROSHA and Dicer1 KO mice exhibit infertility due to abnormal miRNA expression. However, the roles of individual miRNAs in spermatogenesis remain elusive. Here we demonstrated that miR-15b, a member of the miR-15/16 family, is primarily expressed in testis. A miR-15b transgenic mouse model was constructed to investigate the role of miR-15b in spermatogenesis. Impaired spermatogenesis was observed in miR-15b transgenic mice, suggesting that appropriate expression of miR-15b is vital for spermatogenesis. Furthermore, we demonstrated that overexpression of miR-15b reduced CDC25A gene post-transcriptional activity by targeting the 3'-UTR region of CDC25A, thus regulating spermatogenesis. In vitro results further demonstrated that a mutation in CFTR could affect the interaction between Ago2 with Dicer1 and that Dicer1 activity regulates miR-15b expression. We extended our study to azoospermia patients and found that infertile patients have a significantly higher level of miR-15b in semen and plasma samples. Taken together, we propose that CFTR regulation of miR-15b could be involved in the post-transcriptional regulation of CDC25A in mammalian testis and that miR-15b is important for spermatogenesis. Summary Sentence CFTR regulation of miR-15b is involved in the post-transcriptional regulation of CDC25A in mammalian testis and that miR-15b is important for spermatogenesis
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