Relative impact of oxidative stress on the functional competence and genomic integrity of human spermatozoa
Relative impact of oxidative stress on the functional competence and genomic integrity of human spermatozoa
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DOI：
10.1095/biolreprod59.5.1037
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发表时间：
1998-11-01
影响因子：
3.6
通讯作者：
Irvine, DS
中科院分区：
文献类型：
--
作者：
Aitken, RJ;Gordon, E;Irvine, DS
众所周知，活性氧代谢物会破坏精子-卵母细胞融合、精子运动和 DNA 完整性。然而，这些元素对氧化应激的相对敏感性尚不清楚。在这项研究中，对人类精子中的这些因素进行了评估，这些精子暴露于通过用 NADPH 刺激内源性氧化剂生成或直接暴露于过氧化氢而达到的氧化应激水平不断增加的情况。在低水平的氧化应激下，DNA断裂显着减少，而精子-卵母细胞融合率显着提高。随着氧化应激水平的增加，精子表现出显着升高的 DNA 损伤水平 (p < 0.001)，但仍继续表现出增强的精子-卵母细胞融合能力。在最高水平的氧化应激下，观察到极高的 DNA 断裂率，但精子的运动和卵母细胞融合能力也相应丧失。这些研究强调氧化还原机制如何根据氧化刺激的强度增强或破坏人类精子的功能和基因组完整性。由于这些品质受到不同程度的影响，因此表现出显着 DNA 损伤的精子仍然能够使卵母细胞受精。这些结果可能对氧化应激相关病例中辅助受孕手术的安全性产生长期影响。
Reactive oxygen metabolites are known to disrupt sperm-oocyte fusion, sperm movement, and DNA integrity; however, the relative sensitivities of these elements to oxidative stress are unknown. In this study these factors were assessed in human spermatozoa exposed to increasing levels of oxidative stress achieved through the stimulation of endogenous oxidant generation with NADPH or direct exposure to hydrogen peroxide. At low levels of oxidative stress, DNA fragmentation was significantly reduced while the rates of sperm-oocyte fusion were significantly enhanced. As the level of oxidative stress increased, the spermatozoa exhibited significantly elevated levels of DNA damage (p < 0.001) and yet continued to express an enhanced capacity for sperm-oocyte fusion. At the highest levels of oxidative stress, extremely high rates of DNA fragmentation were observed but the spermatozoa exhibited a parallel loss in their capacities for movement and oocyte fusion. These studies emphasize how redox mechanisms can either enhance or disrupt the functional and genomic integrity of human spermatozoa depending on the intensity of the oxidative stimulus. Because these qualities are affected at different rates, spermatozoa exhibiting significant DNA damage are still capable of fertilizing the oocyte. These results may have long-term implications for the safety of assisted conception procedures in cases associated with oxidative stress.