OXIDATIVE STRESS AND REPRODUCTIVE FUNCTION: The protection of mammalian spermatozoa against oxidative stress

精子 氧化应激 电容 SOD2 活性氧 超氧化物歧化酶 抗氧化剂 磷脂过氧化氢谷胱甘肽过氧化物酶 谷胱甘肽过氧化物酶 化学 生物化学 超氧化物 生物 精子 细胞生物学 运动性 遗传学
作者
Cristián O’Flaherty,Eleonora Scarlata
出处
期刊:Reproduction [Bioscientifica]
卷期号:164 (6): F67-F78 被引量:53
标识
DOI:10.1530/rep-22-0200
摘要

This review focuses on the enzymatic antioxidant mechanisms to fight oxidative stress by spermatozoa, highlighting the differences among mammalian species. We discuss recent evidence about players that promote and fight oxidative stress and the need for novel strategies to diagnose and treat cases of male infertility associated with oxidative damage of the spermatozoon.The spermatozoon is very sensitive to high reactive oxygen species (ROS) levels due to its limited antioxidant system. A consortium of antioxidant enzymes, including superoxide dismutase (SOD), glutathione peroxidases (GPXs), peroxiredoxins (PRDXs), thioredoxins, and glutathione-S-transferases, is necessary to produce healthy spermatozoa and to maintain sperm quality to ensure motility, capacitation, and DNA integrity. A delicate balance between ROS production and antioxidant enzymes is needed to ensure ROS-dependent sperm capacitation. GPX4 is an essential component of the mitochondrial sheath in mammalian spermatozoa, and GPX5 is a crucial antioxidant defence in the mouse epididymis to protect the sperm genome during the maturation of the spermatozoon. The mitochondrial superoxide (O2·-) production is controlled by SOD2, and the hydrogen peroxide (H2O2) generated by SOD2 activity and peroxynitrite (ONOO-) are scavenged mainly by PRDXs in human spermatozoa. PRDXs regulate the redox signalling necessary for sperm motility and capacitation, particularly by PRDX6. This enzyme is the first line of defence against oxidative stress to prevent lipid peroxidation and DNA oxidation by scavenging H2O2 and ONOO- through its peroxidase activity and repairing oxidized membranes by its calcium-independent phospholipase A2 activity. The success of antioxidant therapy in treating infertility resides in the proper diagnosis of the presence of oxidative stress and which type of ROS are produced. Thus, more research on the molecular mechanisms affected by oxidative stress, the development of novel diagnostic tools to identify infertile patients with oxidative stress, and randomized controlled trials are of paramount importance to generate personalized antioxidant therapy to restore male fertility.
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