摘要
DNA 损坏经常在 subfertile 男性的精子被遇到并且包括损害授精与不利临床的结果的一个范围被相关，破坏 preimplantation 胚胎的开发，流产的增加的率和在子孙的疾病的提高的风险。在人的精子的 DNA 破碎的病原学密切与氧化的底的外观被相关使内收并且损害精子形式的证据。我们假设那个氧化压力阻碍精子形式，与糟糕改变的染色质导致精子的产生。这些有缺点的房间有一个趋势默认到线粒体与活动性损失， caspase 激活， phosphatidylserine exteriorization 和免费激进的产生的激活联系的一条 apoptotic 小径。后者导致类脂化合物 peroxidation 和氧化 DNA 损坏，它然后导致 DNA 破碎和房间死亡。精子的物理体系结构阻止从获得存取到原子 DNA 并且导致它的破碎由于这 apoptotic 进程激活的任何核酸酶。是为这个原因在人的精子遇到的 DNA 损坏的一个多数似乎氧化。给氧化应力似乎在 DNA 损坏的病原学有的重要角色，应该为在这个条件的处理的抗氧化剂有一个重要角色。如果在精子的氧化 DNA 损坏正在提供全身的氧化应力的敏感读出，这些调查结果的含意能在我们试着作为一篇序言在精子最小化 DNA 损坏到帮助概念治疗的立即的目标以外拉长。
DNA damage is frequently encountered in spermatozoa of subfertile males and is correlated with a range of adverse clinical outcomes including impaired fertilization, disrupted preimplantation embryonic development, increased rates of miscarriage and an enhanced risk of disease in the progeny. The etiology of DNA fragmentation in human spermatozoa is closely correlated with the appearance of oxidative base adducts and evidence of impaired spermiogenesis. We hypothesize that oxidative stress impedes spermiogenesis, resulting in the generation of spermatozoa with poorly remodelled chromatin. These defective cells have a tendency to default to an apeptotic pathway associated with motility loss, caspase activation, phosphatidylserine exteriorization and the activation of free radical generation by the mitochondria. The latter induces lipid peroxidation and oxidative DNA damage, which then leads to DNA fragmentation and cell death. The physical architecture of spermatozoa prevents any nucleases activated as a result of this apoptotic process from gaining access to the nuclear DNA and inducing its fragmentation. It is for this reason that a majority of the DNA damage encountered in human spermatozoa seems to be oxidative. Given the important role that oxidative stress seems to have in the etiology of DNA damage, there should be an important role for antioxidants in the treatment of this condition. If oxidative DNA damage in spermatozoa is providing a sensitive readout of systemic oxidative stress, the implications of these findings could stretch beyond our immediate goal of trying to minimize DNA damage in spermatozoa as a prelude to assisted conception therapy.
