Cystic fibrosis transmembrane conductance regulator is vital to sperm fertilizing capacity and male fertility.
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.
Xu
Wen Ming
WM
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.
Shi
Qi Xian
QX
Chen
Wen Ying
WY
Zhou
Chen Xi
CX
Ni
Ya
Y
Rowlands
Dewi Kenneth
DK
Yi Liu
Guo
G
Zhu
Hu
H
Ma
Ze Gang
ZG
Wang
Xiao Fei
XF
Chen
Zhang Hui
ZH
Zhou
Si Chang
SC
Dong
Hong Shan
HS
Zhang
Xiao Hu
XH
Chung
Yiu Wa
YW
Yuan
Yu Ying
YY
Yang
Wan Xi
WX
Chan
Hsiao Chang
HC
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*
D001639:Bicarbonates; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000242:Cyclic AMP