Cobley James N
Redox Biology Group, Institute for Health Sciences, University of the Highlands and Islands, Old Perth Road, Inverness IV2 3JH, UK.
Antioxidants (Basel). 2020 Sep 29;9(10):933. doi: 10.3390/antiox9100933.
The consensus that assisted reproduction technologies (ART), like in vitro fertilization, to induce oxidative stress (i.e., the known) belies how oocyte/zygote mitochondria-a major presumptive oxidative stressor-produce reactive oxygen species (ROS) with ART being unknown. Unravelling how oocyte/zygote mitochondria produce ROS is important for disambiguating the molecular basis of ART-induced oxidative stress and, therefore, to rationally target it (e.g., using site-specific mitochondria-targeted antioxidants). I review the known mechanisms of ROS production in somatic mitochondria to critique how oocyte/zygote mitochondria may produce ROS (i.e., the unknown). Several plausible site- and mode-defined mitochondrial ROS production mechanisms in ART are proposed. For example, complex I catalyzed reverse electron transfer-mediated ROS production is conceivable when oocytes are initially extracted due to at least a 10% increase in molecular dioxygen exposure (i.e., the intriguing). To address the term oxidative stress being used without recourse to the underlying chemistry, I use the species-specific spectrum of biologically feasible reactions to define plausible oxidative stress mechanisms in ART. Intriguingly, mitochondrial ROS-derived redox signals could regulate embryonic development (i.e., their production could be beneficial). Their potential beneficial role raises the clinical challenge of attenuating oxidative damage while simultaneously preserving redox signaling. This discourse sets the stage to unravel how mitochondria produce ROS in ART, and their biological roles from oxidative damage to redox signaling.
辅助生殖技术(ART),如体外受精,会引发氧化应激(即已知情况),但对于卵母细胞/合子线粒体(主要假定的氧化应激源)如何在ART过程中产生活性氧(ROS)却尚不清楚,这种共识掩盖了这一事实。弄清楚卵母细胞/合子线粒体如何产生活性氧对于阐明ART诱导氧化应激的分子基础至关重要,因此也有助于合理地针对这一问题(例如,使用位点特异性线粒体靶向抗氧化剂)。我回顾了体细胞线粒体中产生活性氧的已知机制,以批判卵母细胞/合子线粒体可能产生活性氧的方式(即未知情况)。提出了几种在ART中可能的、基于位点和模式定义的线粒体活性氧产生机制。例如,当最初提取卵母细胞时,由于分子态二氧暴露至少增加10%,由复合体I催化的反向电子传递介导的活性氧产生是可以想象的(即引人关注的情况)。为了解决在不涉及潜在化学过程的情况下使用氧化应激这一术语的问题,我使用生物学上可行反应的物种特异性光谱来定义ART中可能的氧化应激机制。有趣的是,线粒体活性氧衍生的氧化还原信号可能调节胚胎发育(即它们的产生可能是有益的)。它们潜在的有益作用带来了在减轻氧化损伤的同时保留氧化还原信号的临床挑战。这一论述为揭示线粒体在ART中如何产生活性氧以及它们从氧化损伤到氧化还原信号的生物学作用奠定了基础。