CFTR is essential for sperm fertilizing capacity and is correlated with sperm quality in humans.
BACKGROUND
Our previous studies have demonstrated the cystic fibrosis transmembrane conductance regulator (CFTR) is important for capacitation and male fertility in mouse and guinea pig spermatozoa. However, the exact function of CFTR on human sperm fertilizing capacity, and correlation with sperm quality has not been established. The present study may shed light on some unexplained male infertility, and on a possible new method for diagnosis of male infertility and strategy for male contraception.


METHODS
To assess the effect of CFTR on human sperm fertilizing capacity, we examined sperm capacitation and the acrosome reaction using chlortetracycline staining, analyzed sperm hyperactivation by computer-assisted semen analysis (CASA), measured intracellular cAMP levels using ElA and evaluated sperm penetration of zona-free hamster eggs assay in fertile men. The percentage of spermatozoa expressing CFTR from fertile, healthy and infertile men (mainly teratospermic, asthenoteratospermic, asthenospermic and oligospermic) was conducted by indirect immunofluorescence staining.


RESULTS
Progesterone significantly facilitated human sperm capacitation and ZP3 triggered the acrosome reaction, both were significantly inhibited by CFTR inhibitor-172 (CFTRinh-172; 10 nM-1 microM) in a dose-dependent manner. The presence of 100 nM CFTRinh-172 markedly depressed intracellular cAMP levels, sperm hyperactivation and sperm penetration of zona-free hamster eggs. In addition, the percentage of spermatozoa expressing CFTR in the fertile men was significantly higher than healthy and infertile men categories (P < 0.01).


CONCLUSIONS
CFTR is essential for human sperm fertilizing capacity and the impairment of CFTR expression in spermatozoa is correlated with a reduction of sperm quality. These results suggest that defective expression of CFTR in human sperm may lead to the reduction of sperm fertilizing capacity.
Li
Chu-Yan
CY
Unit of Reproductive Physiology, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang 310013, China.
Jiang
Ling-Ying
LY
Chen
Wen-Ying
WY
Li
Kun
K
Sheng
Hui-Qiang
HQ
Ni
Ya
Y
Lu
Jian-Xin
JX
Xu
Wan-Xiang
WX
Zhang
Song-Ying
SY
Shi
Qi-Xian
QX
D020101:Acrosome Reaction / Q000187:drug effects; D000328:Adult; D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D007248:Infertility, Male / Q000503:physiopathology*; D008297:Male; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D055101:Semen Analysis; D013075:Sperm Capacitation / Q000187:drug effects*; D013081:Sperm Motility / Q000187:drug effects; D013084:Sperm-Ovum Interactions / Q000187:drug effects*; D013094:Spermatozoa / Q000378:metabolism*; D053778:Thiazolidines / Q000494:pharmacology
C482900:3-((3-trifluoromethyl)phenyl)-5-((3-carboxyphenyl)methylene)-2-thioxo-4-thiazolidinone; D001565:Benzoates; D053778:Thiazolidines; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D011374:Progesterone; D000242:Cyclic AMP