Decreased expression of cystic fibrosis transmembrane conductance regulator impairs sperm quality in aged men
Decreased expression of cystic fibrosis transmembrane conductance regulator impairs sperm quality in aged men
复制标题
囊性纤维化跨膜电导调节因子表达的减少会损害老年男性的精子质量。
DOI：
10.1530/rep-13-0146
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发表时间：
2013-12-01
期刊：
影响因子：
3.8
通讯作者：
Cai, Zhiming
中科院分区：
文献类型：
--
作者：
Diao, Ruiying;Fok, Kin Lam;Cai, Zhiming
精子质量随着年龄的增长而下降;然而，潜在的分子机制仍然难以捉摸。囊性纤维化跨膜传导调节因子（CFTR）已被证明在精子的吸收能力和男性生育力中起重要作用。本研究旨在探讨年龄依赖性CFTR下调在老年精子质量下降中的作用。招募了三个年龄组（20-40岁，n=64; 40-60岁，n=61;和>60岁，n=76）的201名健康生育男性。RT-PCR、免疫印迹和免疫荧光染色检测CFTR的表达。收集的精子用CFTR抑制剂或增强剂处理。精子质量通过活动力和碳酸氢盐诱导的获能来评估。结果表明，CFTR在精子赤道段和颈部的表达量随年龄的增长而显著降低。老年男性精子CFTR表达的减少与精子获能所需的前向运动力降低和HCO 3（-）敏感性降低相关。染料木黄酮激活CFTR部分挽救了老年男性精子前向运动能力下降。精子中CFTR表达的降低也与衰老小鼠精子质量的降低有关。这些结果表明，精子中CFTR的年龄依赖性下调导致老年精子的精子质量降低。CFTR可能是一个潜在的挽救精子活力的靶点，也是老年男性生育力的指标。
Sperm quality declines with aging; however, the underlying molecular mechanism remains elusive. The cystic fibrosis transmembrane conductance regulator (CFTR) has been shown to play an essential role in fertilizing capacity of sperm and male fertility. This study aimed to investigate the involvement of age-dependent CFTR downregulation in lowering sperm quality in old age. Two hundred and one healthy fertile men of three age groups (20-40 years, n=64; 40-60 years, n=61; and >60 years, n=76) were recruited. Expression of CFTR was determined by RT-PCR, western blot, and immunofluorescence staining. Collected sperm were treated with CFTR inhibitor or potentiator. Sperm quality was assessed by motility and bicarbonate-induced capacitation. The results showed that the expression of CFTR on the equatorial segment and neck region of sperm was significantly decreased in an age-dependent manner. Reduction of CFTR expression in sperm from old men was correlated with lowered forward motility and decreased HCO3(-) sensitivity required for sperm capacitation. Activation of CFTR by genistein partially rescued the decreased forward motility in sperm from old men. Decreased CFTR expression in sperm was also found to be associated with lowered sperm quality in aging mice. These results suggest that age-dependent downregulation of CFTR in sperm leads to lowered sperm quality in old age sperm. CFTR may be a pontential target for rescuing sperm motility as well as a fertility indicator in old age men.