Impact of Oxidative Stress in Fetal Programming

Abstract

Intrauterine stress induces increased risk of adult disease through fetal programming mechanisms. Oxidative stress can be generated by several conditions, such as, prenatal hypoxia, maternal under- and overnutrition, and excessive glucocorticoid exposure. The role of oxidant molecules as signaling factors in fetal programming via epigenetic mechanisms is discussed. By linking oxidative stress with dysregulation of specific target genes, we may be able to develop therapeutic strategies that protect against organ dysfunction in the programmed offspring.

Low-Dose Gamma Irradiation Enhances Superoxide Anion Production by Nonirradiated Cells Through TGF-β1-Dependent Bystander Signaling

“…Numerous studies have demonstrated that ROS scavengers such as n-acetylcysteine and tempol prevent epigenetic DNA methylation changes induced by oxidative stress (149)(150)(151). Similarly, oxidative stress mediated by intrauterine hypoxia was shown to be protected by administering DNMT inhibitors (137) or methyl donors such as genistein (152,153). Taken together, these studies demonstrate that exogenous application of antioxidant supplements protects the biological system by preventing aberrant epigenetic transformations.…”

“…Numerous epidemiological studies support the role of oxidative stress as a mechanistic basis for fetal programing (137)(138)(139). For example, low birth weight is often associated with elevated oxidative stress during intrauterine development, resulting in cardiovascular disease and type 2 diabetes in adulthood (140).…”

The Level of an Intracellular Antioxidant during Development Determines the Adult Phenotype in a Bird Species: A Potential Organizer Role for Glutathione

“…Nonetheless, many authors (reviews in Luo et al 2006;Nuyt and Alexander 2009;Tarry-Adkins et al 2009;Dennery 2010;Hernandez-García et al 2010;Warner and Ozanne 2010;Thompson and Al-Hasan 2012) have noted that most of the cited mechanisms involve oxidative stress, which is the imbalance between the production of reactive species by cell metabolism or immune responses and the state and availability of antioxidant defenses (Halliwell and Gutteridge 2007). Oxidative stress was initially proposed as one of the main proximate causes of aging (e.g., Kirkwood and Austad 2000).…”

MECHANISMS IN ENDOCRINOLOGY: Nutrition as a mediator of oxidative stress in metabolic and reproductive disorders in women

“…Oxidative stress has been proposed as a potential mediator of nutrition-induced epigenetic changes through various experimental models (40). Maternal malnutrition, obesity or obesogenic maternal diet during gestation, but not during postweaning period (41), was associated with increased oxidative stress markers and impaired antioxidant capacity in the offspring, making them vulnerable to diabetogenic effects (42,43).…”