CFTR is essential for sperm fertilizing capacity and is correlated with sperm quality in humans
CFTR is essential for sperm fertilizing capacity and is correlated with sperm quality in humans
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CFTR 对于精子受精能力至关重要，并且与人类精子质量相关
DOI：
10.1093/humrep/dep406
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发表时间：
2010-02-01
影响因子：
6.1
通讯作者：
Shi, Qi-Xian
中科院分区：
文献类型：
--
作者：
Li, Chu-Yan;Jiang, Ling-Ying;Shi, Qi-Xian
我们以前的研究已经证明囊性纤维化跨膜传导调节因子（CFTR）对小鼠和豚鼠精子的获能和雄性生育力非常重要。然而，CFTR对人类精子活力的确切作用以及与精子质量的相关性尚未确定。本研究采用金霉素染色法检测精子获能和顶体反应，计算机辅助精液分析（CASA）检测精子超活化，用ElA测定细胞内cAMP水平，并在有生育能力的男性中评价精子穿透无透明带仓鼠卵的试验。用间接免疫荧光染色法检测了正常、生育和不育男性（主要是畸形精子症、弱畸形精子症、弱精子症和少精子症）精子表达CFTR的百分率，结果表明，孕酮显著促进人精子获能，ZP 3触发顶体反应，CFTR抑制剂172（CFTRinh-172; 10 nM-1 μ M）以剂量依赖方式显著抑制这两种作用。100 nM CFTRinh-172的存在显著抑制了无透明带仓鼠卵的细胞内cAMP水平、精子超活化和精子穿透。生育组精子表达CFTR的百分率显著高于健康组和不育组（P < 0.01），CFTR是人类精子活力所必需的，精子CFTR表达受损与精子质量下降有关。这些结果表明，CFTR在人类精子中的表达缺陷可能导致精子精子活力的降低。
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.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.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 mu M) 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).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.