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学科主题: 临床医学
题名:
Defective CFTR-Dependent CREB Activation Results in Impaired Spermatogenesis and Azoospermia
作者: Xu, Wen Ming1,2; Chen, Jing2; Chen, Hui2; Diao, Rui Ying2,3; Fok, Kin Lam2; Dong, Jian Da2; Sun, Ting Ting2; Chen, Wen Ying2,4; Yu, Mei Kuen2; Zhang, Xiao Hu2; Tsang, Lai Ling2; Lau, Ann2; Shi, Qi Xian4; Shi, Qing Hua5; Huang, Ping Bo6; Chan, Hsiao Chang1,2
刊名: PLOS ONE
发表日期: 2011-05-09
DOI: 10.1371/journal.pone.0019120
卷: 6, 期:5
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
关键词[WOS]: TRANSMEMBRANE CONDUCTANCE REGULATOR ; SOLUBLE ADENYLYL-CYCLASE ; CYSTIC-FIBROSIS GENE ; TRANSCRIPTION FACTORS ; CONGENITAL ABSENCE ; INFERTILE MEN ; SPERM QUALITY ; VAS-DEFERENS ; HEALTHY-MEN ; GERM-CELLS
英文摘要:

Cystic fibrosis (CF) is the most common life-limiting recessive genetic disease among Caucasians caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) with over 95% male patients infertile. However, whether CFTR mutations could affect spermatogenesis and result in azoospermia remains an open question. Here we report compromised spermatogenesis, with significantly reduced testicular weight and sperm count, and decreased cAMP-responsive element binding protein (CREB) expression in the testes of CFTR knockout mice. The involvement of CFTR in HCO3- transport and the expression of the HCO3- sensor, soluble adenylyl cyclase (sAC), are demonstrated for the first time in the primary culture of rat Sertoli cells. Inhibition of CFTR or depletion of HCO3- could reduce FSH-stimulated, sAC-dependent cAMP production and phosphorylation of CREB, the key transcription factor in spermatogenesis. Decreased CFTR and CREB expression are also observed in human testes with azoospermia. The present study reveals a previously undefined role of CFTR and sAC in regulating the cAMP-CREB signaling pathway in Sertoli cells, defect of which may result in impaired spermatogenesis and azoospermia. Altered CFTR-sAC-cAMP-CREB functional loop may also underline the pathogenesis of various CF-related diseases.

语种: 英语
所属项目编号: 30770817 ; 2006CB504002
项目资助者: National Natural Science Foundation of China ; South China National Research Center for Integrated Biosciences ; Sun Yat-sen University ; National 973 projects ; Focused Investment Scheme ; Li Ka Shing Institute of Health Sciences of The Chinese University of Hong Kong ; Morningside Foundation
WOS记录号: WOS:000290386800008
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/56023
Appears in Collections:北京大学深圳医院_期刊论文

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作者单位: 1.Sichuan Univ, Chinese Univ Hong Kong, W China Inst Women & Childrens Hlth, Joint Lab Reprod Med,W China Univ Hosp 2, Chengdu 610064, Peoples R China
2.Chinese Univ Hong Kong, Sch Biomed Sci, Epithelial Cell Biol Res Ctr, Fac Med, Hong Kong, Hong Kong, Peoples R China
3.Peking Univ, Shenzhen Key Lab Male Reprod & Genet, Shenzhen Hosp, Shenzhen, Peoples R China
4.Zhejiang Acad Med Sci, Dept Reprod Physiol, Hangzhou, Zhejiang, Peoples R China
5.Univ Sci & Technol China, Lab Mol & Cell Genet, Hefei Natl Lab Phys Sci Microscale, Sch Life Sci, Hefei 230026, Peoples R China
6.Hong Kong Univ Sci & Technol, Dept Biol, Hong Kong, Hong Kong, Peoples R China

Recommended Citation:
Xu, Wen Ming,Chen, Jing,Chen, Hui,et al. Defective CFTR-Dependent CREB Activation Results in Impaired Spermatogenesis and Azoospermia[J]. PLOS ONE,2011,6(5).
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