title: 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.
authors.affiliation: Epithelial Cell Biology Research Center, Li Ka Shing Institute of Health Sciences, Department of Physiology, Faculty of Medicine, Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
authors.forename: Wen Ming
authors.initials: WM
authors.lastname: Xu
authors.forename: Qi Xian
authors.initials: QX
authors.lastname: Shi
authors.forename: Wen Ying
authors.initials: WY
authors.lastname: Chen
authors.forename: Chen Xi
authors.initials: CX
authors.lastname: Zhou
authors.forename: Ya
authors.initials: Y
authors.lastname: Ni
authors.forename: Dewi Kenneth
authors.initials: DK
authors.lastname: Rowlands
authors.forename: Guo
authors.initials: G
authors.lastname: Yi Liu
authors.forename: Hu
authors.initials: H
authors.lastname: Zhu
authors.forename: Ze Gang
authors.initials: ZG
authors.lastname: Ma
authors.forename: Xiao Fei
authors.initials: XF
authors.lastname: Wang
authors.forename: Zhang Hui
authors.initials: ZH
authors.lastname: Chen
authors.forename: Si Chang
authors.initials: SC
authors.lastname: Zhou
authors.forename: Hong Shan
authors.initials: HS
authors.lastname: Dong
authors.forename: Xiao Hu
authors.initials: XH
authors.lastname: Zhang
authors.forename: Yiu Wa
authors.initials: YW
authors.lastname: Chung
authors.forename: Yu Ying
authors.initials: YY
authors.lastname: Yuan
authors.forename: Wan Xi
authors.initials: WX
authors.lastname: Yang
authors.forename: Hsiao Chang
authors.initials: HC
authors.lastname: Chan
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000378:metabolism; D005306:Fertilization / Q000235:genetics*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008856:Microscopy, Fluorescence; D009154:Mutation / Q000235:genetics; D013075:Sperm Capacitation / Q000235:genetics*; D013081:Sperm Motility / Q000235:genetics; D013094:Spermatozoa / Q000737:chemistry*
chemical_list: D001639:Bicarbonates; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000242:Cyclic AMP