NDLI: Defective CFTR-Dependent CREB Activation Results in Impaired Spermatogenesis and Azoospermia

Content Provider	PubMed Central
Author	Xu, Wen Ming Chen, Jing Chen, Hui Diao, Rui Ying Fok, Kin Lam Dong, Jian Da Sun, Ting Ting Chen, Wen Ying Yu, Mei Kuen Zhang, Xiao Hu Tsang, Lai Ling Lau, Ann Shi, Qi Xian Shi, Qing Hua Huang, Ping Bo Chan, Hsiao Chang
Editor	Irina, Agoulnik
Copyright Year	2011
Abstract	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.
Related Links	http://dx.doi.org/10.1371/journal.pone.0019120
Starting Page	19120
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	5
Volume Number	6
Language	English
Publisher	Public Library of Science
Publisher Date	2011-05-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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