據(jù)香港中通社報道,，香港中文大學(xué)研究人員在精子里發(fā)現(xiàn)一個上皮細(xì)胞離子信道,，可能影響男性生育能力。他們之前的研究證明,，同樣的離子信道表達于女性生殖道,，如果有功能缺陷，會導(dǎo)致女性不育,。
這項新的研究結(jié)果已在線刊于權(quán)威學(xué)術(shù)期刊美國科學(xué)院院刊,。
精子必須經(jīng)過一個啟動的過程才能使卵子受精，這過程稱為精子獲能,。這個精子獲能的過程已知是由碳酸氫鹽誘發(fā),。由陳小章教授領(lǐng)導(dǎo)的香港中文大學(xué)上皮細(xì)胞生物學(xué)研究中心的研究人員，與浙江醫(yī)學(xué)科學(xué)院合作,，證實囊性纖維化跨膜電導(dǎo)調(diào)節(jié)器(CFTR)負(fù)責(zé)輸送碳酸氫根進入精子，對精子授精能力及男性生育能力非常重要,。
CFTR是一個陰離子信道,，其基因突變會導(dǎo)致囊性纖維化,，因為氯離子和碳酸氫根(HCO3-)分泌缺陷，引發(fā)一系列器官病征,。
香港中文大學(xué)上皮細(xì)胞生物學(xué)研究中心較早的研究已證實CFTR存在于女性生殖道上,，其功能失效可阻止精子在女性生殖道內(nèi)的獲能。
百分之九十五患上囊性纖維化的男性病人,，因先天性無輸精管而不育,，但囊性纖維化跨膜電導(dǎo)調(diào)節(jié)器基因突變會否導(dǎo)致其它類型的男性不育，仍有爭議,。研究人員首次在人類和老鼠的精子發(fā)現(xiàn)CFTR,。CFTR抑制劑或抗體能有效減低精子獲能，及相關(guān)的碳酸氫根依賴反應(yīng),；研究人員又證實CFTR突變老鼠,，其精子授精能力大大比野生型老鼠為低。
研究結(jié)果顯示,，精子的CFTR功能為碳酸氫根的傳輸,，促使精子獲能；而CFTR基因突變引致功能失效,，會降低精子授精能力,，這是先天性無輸精管以外另一導(dǎo)致男性不育的可能因素。
研究同時顯示,，CFTR缺陷可以對男性不育造成不同程度的影響,，目前已知的與CFTR相關(guān)的基因突變逾二千種，研究結(jié)果可能為許多未明原因的男性不育個案提供新的解釋,，并提供診斷的新靶子,。
原始出處:
PNAS Published online before print May 22, 2007
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0609253104
Medical Sciences
Cystic fibrosis transmembrane conductance regulator is vital to sperm fertilizing capacity and male fertility
( bicarbonate | CFTR | sperm capacitation )
Wen Ming Xu *, Qi Xian Shi , Wen Ying Chen *, Chen Xi Zhou *, Ya Ni , Dewi Kenneth Rowlands *, Guo Yi Liu , Hu Zhu *, Ze Gang Ma *, Xiao Fei Wang , Zhang Hui Chen , Si Chang Zhou , Hong Shan Dong *, Xiao Hu Zhang *, Yiu Wa Chung *, Yu Ying Yuan , Wan Xi Yang , and Hsiao Chang Chan *¶
*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; Zhejiang Academy of Medical Sciences, Hangzhou 310013, China; Zhejiang University School of Medicine, College of Life Sciences, Hangzhou 310058, China; and Department of Physiology, Harbin Medical University, Harbin 150086, China
Edited by Ryuzo Yanagimachi, University of Hawaii, Honolulu, HI, and approved April 16, 2007 (received for review October 23, 2006)
Abstract
Cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel, mutations of which cause cystic fibrosis, a disease characterized by defective Cl- and HCO3- 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 HCO3--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 HCO3- 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.
