Ollero M, Gil-Guzman E, Lopez M C, Sharma R K, Agarwal A, Larson K, Evenson D, Thomas A J, Alvarez J G
Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
Hum Reprod. 2001 Sep;16(9):1912-21. doi: 10.1093/humrep/16.9.1912.
Reactive oxygen species (ROS)-induced damage of membrane phospholipids and DNA in human spermatozoa has been implicated in the pathogenesis of male infertility. In this study, variations in ROS production, DNA structure (as measured by the sperm chromatin structure assay) and lipid composition, were studied in human spermatozoa at different stages of maturation.
Sperm subsets were isolated by discontinuous density gradient centrifugation of semen samples obtained from healthy donors and from infertility patients.
DNA damage and ROS production were highest in immature spermatozoa with cytoplasmic retention and abnormal head morphology, and lowest in mature spermatozoa. Docosahexaenoic acid and sterol content were highest in immature germ cells and immature spermatozoa, and lowest in mature spermatozoa. The relative proportion of ROS-producing immature spermatozoa in the sample was directly correlated with DNA damage in mature spermatozoa, and inversely correlated with the recovery of motile spermatozoa. There was no correlation between DNA damage and sperm morphology in mature spermatozoa.
The high levels of ROS production and DNA damage observed in immature spermatozoa may be indicative of derangements in the regulation of spermiogenesis. DNA damage in mature spermatozoa may be the result of oxidative damage by ROS-producing immature spermatozoa during sperm migration from the seminiferous tubules to the epididymis.
活性氧（ROS）诱导的人类精子膜磷脂和DNA损伤与男性不育的发病机制有关。在本研究中，我们研究了人类精子在不同成熟阶段ROS产生、DNA结构（通过精子染色质结构分析测量）和脂质组成的变化。
通过对从健康供体和不育患者获得的精液样本进行不连续密度梯度离心来分离精子亚群。
在具有细胞质残留和头部形态异常的未成熟精子中，DNA损伤和ROS产生最高，而在成熟精子中最低。二十二碳六烯酸和甾醇含量在未成熟生殖细胞和未成熟精子中最高，而在成熟精子中最低。样本中产生ROS的未成熟精子的相对比例与成熟精子中的DNA损伤直接相关，与活动精子的回收率呈负相关。成熟精子中的DNA损伤与精子形态之间没有相关性。
在未成熟精子中观察到的高水平ROS产生和DNA损伤可能表明精子发生调节紊乱。成熟精子中的DNA损伤可能是未成熟精子在从生精小管迁移到附睾过程中产生的ROS氧化损伤的结果。
