男性不孕症的診療與精蟲活化及染色質品質密切相關，而氧化自由基在精蟲染色質的損壞又扮有關鍵的角色，故學者呼籲對於不孕症患者的診療上，應包括氧化壓力及染色質損壞的檢驗，甚至建議精蟲製備時，可加入抗氧化物以保護精蟲染色質免於破壞。但許多研究報告指出，氧化自由基為精子活化過程中最早出現的訊息傳遞訊號，加入抗氧化物去除自由基，反而可能影響精蟲活動能力；因此設計本研究計畫以釐清氧化自由基及抗氧化物對於精蟲活化及染色質損壞的影響。本研究計畫將先探討氧化壓力對於體外受精的精子活化過程及受精率的影響程度，以評估氧化壓力加入精液分析項目的必要性。第二年則是針對精液分析正常且生育過的男性於體外加入自由基及相對的抗氧化酵素，探討自由基及抗氧化能力於精子活化過程的消長，評估自由基對於精子過動能力及透明層結合能力的影響，同時探討精蟲染色質染色質損壞與細胞凋亡訊息傳遞之間的關係。第三年則對於活動力較差的男性不孕症患者，評估體外精子製備方式加入抗氧化物之效率，同時探討精子活化的狀況，以及對精蟲染色質的影響。藉此研究計畫釐清氧化自由基及抗氧化物對於精蟲活化的影響並評估加入抗氧化物的應用價值，以期能幫助婦女懷孕，並提升胎兒及寶寶的健康。 The diagnosis and treatment of male infertility are intimately connected with sperm capacitation and integrity of chromatin. Reactive oxygen species (ROS) is a key player for chromatin damage of spermatozoa. The research community suggests the application of advance semen analysis, including oxidative stress and chromatin damage, for certain infertile couples. Furthermore, the supplement of antioxidants during sperm preparation may benefit infertile couples. However, ROS is the initial signal molecule for sperm capacitation. Elimination of ROS by antioxidants may result in capacitation impairment or failure. In this proposal, we will evaluate the effect of ROS and antioxidant capacity on sperm capacitation in order to determinate the necessity to measure ROS levels in semen analysis. Second, we will evaluate the effect of exogenous ROS and antioxidant enzymes on sperm capacitation and chromatin damage of spermatozoa from male partners of infertile couples with normal results of semen analysis. Third, we will evaluate the efficiency of antioxidants for sperm capacitation and chromatin integrity of spermatozoa from patients with asthenozoospermia. By this study, we attempt to elucidate the patho-physiology of ROS on sperm capacitation and chromatin integrity and to evaluate the pros and cons of antioxidants supplement during sperm preparation.
