ATM/H2AX与冷冻精子DNA损伤修复

ATM/H2AX and repair of sperm-DNA damage during cryopreservation

精液冷冻保存是辅助生殖领域中的一项重要技术,但冷冻本身可引起精子DNA损伤,其中过量活性氧(reactive oxygen species,ROS)的生成起主要作用;而DNA损伤精子仍可以受精形成胚胎,影响生殖结局。蛋白激酶ATM(ataxia-telangiectasia mutated)是DNA损伤的信号感受器,可启动级联反应磷酸化多种蛋白分子调控DNA损伤修复和细胞周期检查点。在ATM的下游分子中,组蛋白H2AX(histone H2AX)被磷酸化激活后参与了DNA损伤精子受精后的修复,与ATM相互作用共同调控胚胎发育过程的细胞周期。ATM/H2AX参与DNA损伤修复以及细胞周期检查点信号转导,以及在氧化应激性DNA损伤修复中的潜在作用,提示其可能参与了冷冻精子氧化应激性DNA损伤的修复过程。

Semen cryopreservation is an important method in assisted reproductive technology, but meanwhile it is complicated by cryodamage to spermatozoa. Mechanisms behind the cryodamage to spermatozoa are thought to be maltifactorial, and the excessive generation of reactive oxygen species （ROS） has been suggested as a major zontributing factor. DNA-damaged sperm is also capable of fertilizing oocytes, significantly affecting the outcome of reproduction. As a sensor of DNA damage responses, protein kinase ATM （ataxia telangieetasia mutated） can be initiated through rapid intermolecular autophosphorylation induced by DNA damage, phosphorylate various proteins, and amplify the responses to DNA damage. After DNA damage, histone H2AX is activated by ATM, which contributes to the repair of sperm-DNA damage after fertilization and regulates the cell cycle during embryo development. Given the important role of the ATM/H2AX signaling pathway in the response to and repair of DNA damage induced by oxidative stress, it may mediate the repair of sperm-DNA damage resuhing from cryopreservation.