Department of Surgery (Urology Division), McGill University, Montréal, Québec, Canada.
Pharmacology and Therapeutics, Faculty of Medicine, McGill University, Montréal, Québec, Canada.
Biol Reprod. 2017 Oct 1;97(4):577-585. doi: 10.1093/biolre/iox104.
Cellular response to reactive oxygen species (ROS) includes both reversible redox signaling and irreversible nonenzymatic reactions which depend on the nature and concentration of the ROS involved. Changes in thiol/disulfide pairs affect protein conformation, enzymatic activity, ligand binding, and protein-protein interactions. During spermatogenesis and epididymal maturation, there are ROS-dependent modifications of the sperm chromatin and flagellar proteins.The spermatozoon is regulated by redox mechanisms to acquire fertilizing ability. For this purpose, controlled amounts of ROS are necessary to assure sperm activation (motility and capacitation). Modifications of the thiol groups redox status of sperm proteins are needed for spermatozoon to achieve fertilizing ability. However, when ROS are produced at high concentrations, the established oxidative stress promotes pathological changes affecting sperm function and leading to infertility. Sperm proteins are sensitive to high levels of ROS and suffer modifications that impact on motility, capacitation, and the ability of the spermatozoon to recognize and bind to the zona pellucida and damage of sperm DNA. Thiol oxidation, tyrosine nitration, and S-glutathionylation are highlighted in this review as significant redox-dependent protein modifications associated with impairment of sperm function and alteration of paternal genome leading to infertility. Peroxiredoxins, the primary antioxidant protection in spermatozoa, are affected by most of the protein modifications described in this review. They play a significant role in both physiological and pathological processes in mammalian spermatozoa.
细胞对活性氧（ROS）的反应包括可逆的氧化还原信号和依赖于所涉及的 ROS 的性质和浓度的不可逆的非酶反应。巯基/二硫键对的变化会影响蛋白质构象、酶活性、配体结合和蛋白质-蛋白质相互作用。在精子发生和附睾成熟过程中，ROS 依赖性修饰精子染色质和鞭毛蛋白。精子受氧化还原机制调节以获得受精能力。为此，需要控制 ROS 的数量以确保精子的激活（运动和获能）。精子蛋白的巯基氧化还原状态的修饰对于精子获得受精能力是必要的。然而，当 ROS 以高浓度产生时，建立的氧化应激会促进影响精子功能并导致不育的病理变化。精子蛋白对高水平的 ROS 敏感，并遭受影响运动、获能以及精子识别和结合透明带的能力和精子 DNA 损伤的修饰。巯基氧化、酪氨酸硝化和 S-谷胱甘肽化在本文中被强调为与精子功能障碍和父本基因组改变相关的重要氧化还原依赖性蛋白修饰，导致不育。过氧化物酶是精子中主要的抗氧化保护，受本文所述大多数蛋白修饰的影响。它们在哺乳动物精子的生理和病理过程中都起着重要的作用。
