CFTR mutation compromises spermatogenesis by enhancing miR-15b maturation and suppressing its regulatory target CDC25A†
| Autor: | Huanxun Yue, Fuping Li, Xiaotong Leung, Wenming Xu, Huijuan Liao, Jiabei He, Yan Chen, Xiang Wang, Xiaoliang Li |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Genetically modified mouse Male CDC25A Cystic Fibrosis Transmembrane Conductance Regulator Mice Transgenic Biology medicine.disease_cause 03 medical and health sciences Mice 0302 clinical medicine microRNA medicine Animals Mice Inbred CFTR cdc25 Phosphatases RNA Processing Post-Transcriptional Spermatogenesis Gene Drosha Infertility Male Azoospermia Mutation 030219 obstetrics & reproductive medicine Cell Biology General Medicine medicine.disease Cell biology Mice Inbred C57BL MicroRNAs 030104 developmental biology Reproductive Medicine Gene Expression Regulation Female |
| Zdroj: | Biology of reproduction. 101(1) |
| ISSN: | 1529-7268 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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