Discipline of Biological Sciences and ARC Centre of Excellence in Biotechnology and Development, School of Environmental and Life Sciences, University of Newcastle, Callaghan, Australia.
Antioxid Redox Signal. 2011 Feb 1;14(3):367-81. doi: 10.1089/ars.2010.3186. Epub 2010 Sep 1.
Defective sperm function is the largest single defined cause of human infertility and one of the major reasons we are witnessing an exponential increase in the uptake of assisted conception therapy in the developed world. A major characteristic of defective human spermatozoa is the presence of large amounts of DNA damage, which is, in turn, associated with reduced fertility, increased rates of miscarriage, and an enhanced risk of disease in the offspring. This DNA damage is largely oxidative and is closely associated with defects in spermiogenesis. To explain the origins of this DNA damage, we postulate that spermiogenesis is disrupted by oxidative stress, leading to the creation of defective gametes with poorly remodeled chromatin that are particularly susceptible to free radical attack. To compound the problem, these defective cells have a tendency to undergo an unusual truncated form of apoptosis associated with high amounts of superoxide generation by the sperm mitochondria. This leads to significant oxidative DNA damage that eventually culminates in the DNA fragmentation we see in infertile patients. In light of the significance of oxidative stress in the etiology of defective sperm function, a variety of antioxidant therapies are now being assessed for their therapeutic potential.
精子功能缺陷是导致人类不孕的最大单一因素，也是我们在发达国家见证辅助受孕疗法使用率呈指数级增长的主要原因之一。人类精子缺陷的一个主要特征是存在大量的 DNA 损伤，这反过来又与生育能力下降、流产率增加以及后代患病风险增加有关。这种 DNA 损伤主要是氧化的，并与精子发生缺陷密切相关。为了解释这种 DNA 损伤的起源，我们假设精子发生受到氧化应激的破坏，导致形成具有不良重塑染色质的有缺陷的配子，这些配子特别容易受到自由基的攻击。更糟糕的是，这些有缺陷的细胞有一种倾向，即发生与精子线粒体产生大量超氧化物有关的异常截短形式的细胞凋亡。这会导致大量的氧化 DNA 损伤，最终导致我们在不育患者中看到的 DNA 碎片化。鉴于氧化应激在精子功能缺陷的病因学中的重要性，现在正在评估各种抗氧化治疗方法的治疗潜力。
