In Utero Oxidative Stress Epigenetically Programs Antioxidant Defense Capacity and Adulthood Diseases

Significance: Maternal health and diet during gestation are critical for predicting fetal outcomes, both immediately at birth and in adulthood. While epigenetic modifications have previously been tightly linked to carcinogenesis, recent advances in the field have suggested that numerous adulthood diseases, including those characteristic of metabolic syndrome, could be programmed in utero in response to maternal exposures, and these programmable diseases are associated with epigenetic modifications of vital genes. Recent Advances: While little is currently known about the epigenetic regulation of the antioxidant (AOX) defense system, several studies in animals show that AOX defense capacity may be programmed in utero, making it likely that the critical genes involved in this pathway are epigenetically regulated, either by DNA methylation or by the modification of histone tails. Critical Issues: This article presents the most current knowledge of the in utero regulation of the AOX defense capacity, and will specifically focus on the potential epigenetic regulation of this system in response to various in utero exposures or stimuli. The ability to appropriately respond to oxidative stress is critical for the health and survival of any organism, and the potential programming of this capacity may provide a link between the in utero environment and the tendency of certain individuals to be more susceptible toward disease stimuli in their postnatal environments. Future Directions: We sincerely hope that future studies which result in a deeper understanding of the in utero programming of the epigenome will lead to novel and effective therapies for the treatment of epigenetically linked diseases. Antioxid. Redox Signal. 17, 237-253.