Redox control of teratogenesis

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.

► Many human teratogens induce oxidative stress and reactive oxygen species production. ► Oxidative stress is not merely an overproduction of reactive oxygen species. ► Oxidative stress can cause malformation without apoptosis. ► A newer definition of oxidative stress would include the disruption of redox-sensitive events. ► Chemical perturbation of redox states alters developmental programming causing malformation.