- 期刊
Mitochondrial DNA Mutation and Depletion Are Associated withDecline of Fertility and Motility of Human Sperm
與人類精子運動活力及授孕力低落相關之粒線體DNA突變與減量
摘要
精子運動活力是決定男性生殖力的重要因子。在這一篇回顧性論文中，我們對最近發現之粒線體DNA突變和減量與精子運動活力與授孕力低落的相關性作一討論。我們是以聚合酵素連鎖反應（PCR）技術及DNA定序法偵測並確立精子的粒腺體DNA突變，而粒線體DNA的拷貝數則以粒線體DNA和核DNA量的比值計算之。運用這些分子生物學技述，我們率先於運動活力及授孕力低落的精子細胞發現一個常見的4977bp粒線體DAN缺失突變和兩個新的7345bp及7599bp粒線體DNA缺失突變。這三種粒線體DNA缺失突變的發生頻率及含量在運動活力及授孕力低落的精子細胞中有明顯增加的現象。另一方面，我們發現運動活力較差的精子細胞其所含的粒線體DNA量較少。以電腦輔助分析一測淂之數種精子運動活力指標分數也與粒線體DNA的拷貝數呈正相關。再者，我們以穿透式電子顯微鏡觀察來自不孕症男性之含粒線體DNA量較少的精子細胞。我們發現超過百分之七十的精子細胞擁有正常螺旋柱狀粒線體的中段結構。這些結果顯示粒腺體DNA減量的精子細胞並不是含較少的粒線體，而是各個粒線體所含之粒線體DNA分子的數目較少。基於以上這些新發現，我們認為精子細胞的粒線體DNA突變和減量可能在某些男性不孕症的致病機轉扮演一重要的角色。
並列摘要
Sperm motility is one of the most important determinants of male fertility. In this review, we discuss recent findings that mutation and depletion of mitochondrial DNA (mtDNA) are associated with poor motility and diminished fertility in human sperm. The mtDNA mutations were identified and characterized by polymerase chain reaction (PCR) techniques and DNA sequencing, and the copy number of mtDNA was determined as the ratio between the amount of mtDNA and that of nuclear DNA in sperm. By use of these molecular techniques we first established that the common 4977-bp deletion and 2 novel deletions of 7345 bp and 7599 bp of mtDNA occur more frequently and in higher proportions in spermatozoa with poorer motility and lower fertility. On the other hand, we found that the copy number of mtDNA is lower for sperm with poorer motility. Scores of several motility parameters of sperm assessed by a computer-assisted semen analyzer are positively correlated with the copy number of mtDNA. Moreover, with a transmission electron microscope we examined spermatozoa with low levels of mtDNA from infertile patients. We found that more than 70% of spermatozoa exhibited normal helicoidal morphology of mitochondria packed in the midpiece. These results indicate that depletion of mtDNA in these spermatozoa is not due to a decrease in the number of mitochondria but is a result of the paucity of the mitochondrial genome per se. On the basis of these recent findings, we suggest that mutation and depletion of mtDNA in spermatozoa may play an important role in the pathophysiology of some male infertility.