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Cystic fibrosis transmembrane conductance regulator is vital to sperm fertilizing capacity and male fertility.

Abstract
Cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel, mutations of which cause cystic fibrosis, a disease characterized by defective Cl(-) and HCO(3)(-) transport. Although >95% of all CF male patients are infertile because of congenital bilateral absence of the vas deferens (CBAVD), the question whether CFTR mutations are involved in other forms of male infertility is under intense debates. Here we report that CFTR is detected in both human and mouse sperm. CFTR inhibitor or antibody significantly reduces the sperm capacitation, and the associated HCO(3)(-)-dependent events, including increases in intracellular pH, cAMP production and membrane hyperpolarization. The fertilizing capacity of the sperm obtained from heterozygous CFTR mutant mice is also significantly lower compared with that of the wild-type. These results suggest that CFTR in sperm may be involved in the transport of HCO(3)(-) important for sperm capacitation and that CFTR mutations with impaired CFTR function may lead to reduced sperm fertilizing capacity and male infertility other than CBAVD.
AuthorsWen Ming Xu, Qi Xian Shi, Wen Ying Chen, Chen Xi Zhou, Ya Ni, Dewi Kenneth Rowlands, Guo Yi Liu, Hu Zhu, Ze Gang Ma, Xiao Fei Wang, Zhang Hui Chen, Si Chang Zhou, Hong Shan Dong, Xiao Hu Zhang, Yiu Wa Chung, Yu Ying Yuan, Wan Xi Yang, Hsiao Chang Chan
JournalProceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 104 Issue 23 Pg. 9816-21 (Jun 05 2007) ISSN: 0027-8424 [Print] United States
PMID17519339 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Bicarbonates
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Cyclic AMP
Topics
  • Analysis of Variance
  • Animals
  • Bicarbonates (metabolism)
  • Cyclic AMP (metabolism)
  • Cystic Fibrosis Transmembrane Conductance Regulator (genetics, metabolism)
  • Fertilization (genetics)
  • Humans
  • Hydrogen-Ion Concentration
  • Male
  • Mice
  • Mice, Mutant Strains
  • Microscopy, Fluorescence
  • Mutation (genetics)
  • Sperm Capacitation (genetics)
  • Sperm Motility (genetics)
  • Spermatozoa (chemistry)

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