Division of Pulmonary, Allergy/Immunology, Cystic Fibrosis and Sleep, Department of Pediatrics, Emory School of Medicine, Emory University, Atlanta, GA 30322, United States.
Reprod Toxicol. 2013 Jan;35:165-79. doi: 10.1016/j.reprotox.2012.09.004. Epub 2012 Oct 23.
A number of human teratogens elicit their deleterious effects through mechanisms involving the generation of reactive oxygen species (ROS) and oxidative stress. However, classic definitions of oxidative stress do not fully coincide with basic fundamental principles of teratology. Newer definitions of oxidative stress focus on the targeted redox modification of cysteine/thiol functional groups found in the regulatory domains of critical signaling pathway proteins, suggesting that the targeted disruption of signaling through specific redox couples may account for the specificity of teratogen-induced malformations which previously could not be rationalized. Here, we review examples of teratogens that induce ROS and oxidative injury, describe oxidative stress-related teratogenic mechanisms, and provide rationale for developmental periods of sensitivity and species susceptibility. Understanding how chemicals disrupt redox status, induce oxidative stress leading to dysmorphogenesis becomes important to identify potential teratogens and develop therapeutic interventions for attenuation of harmful chemical effects in utero following exposure.
许多人类致畸剂通过涉及活性氧（ROS）生成和氧化应激的机制发挥其有害作用。然而，氧化应激的经典定义与致畸学的基本基本原理并不完全一致。氧化应激的新定义侧重于关键信号通路蛋白调节域中半胱氨酸/巯基功能基团的靶向氧化还原修饰，表明通过特定氧化还原对靶向破坏信号可能解释了以前无法合理化的致畸剂诱导畸形的特异性。在这里，我们回顾了诱导 ROS 和氧化损伤的致畸剂的例子，描述了与氧化应激相关的致畸机制，并为敏感性和物种易感性的发育时期提供了依据。了解化学物质如何破坏氧化还原状态，诱导氧化应激导致畸形发生，对于识别潜在的致畸剂以及在暴露后宫内衰减有害化学作用的治疗干预措施变得很重要。
