Impact of oxidative stress during pregnancy on fetal epigenetic patterns and early origin of vascular diseases

Abstract

Epidemiological studies have led scientists to postulate the developmental origins of health and disease hypothesis for noncommunicable diseases such as diabetes, cardiovascular diseases, hypertension, and obesity. However, the cellular and molecular mechanisms involved in the development of these diseases are not well understood. In various animal models, it has been observed that oxidative stress during pregnancy is associated with the early development of endothelial dysfunction in offspring. This phenomenon suggests that endothelial dysfunction may initiate in the uterus and could lead to increased risk of cardiovascular disease later in life. Currently, it is known that many of the fetal adaptive responses to environmental factors are mediated by epigenetic changes in the genome, especially by the degree of methylation in cytosines in the promoter regions of genes. These findings suggest that the establishment of a particular epigenetic pattern in the genome may be generated by oxidative stress.

Interplay between Oxidative Stress and Nutrient Sensing Signaling in the Developmental Origins of Cardiovascular Disease

“…It has been well established that endothelial dysfunction is central to the development of CVD [24]. Third, there are studies that show that redox signaling and NO control epigenetic regulation, contributing to cardiovascular programming [79]. Fourth, there are many reports that NO-ROS imbalance plays a crucial role in several models of glucocorticoid-induced programmed hypertension [52,53,80,81,82].…”

Keap1–Nrf2 regulated redox signaling in utero: Priming of disease susceptibility in offspring

“…As oxidative stress is associated with a large number of other chronic diseases, including diabetes [118], further research is warranted to elucidate the role of epigenetic mechanisms in Keap1-Nrf2 signaling in health and disease. Emerging evidence implicates impaired Nrf2 signaling and/or Nrf2 epigenetic regulation in various diabetic pathologies [16, [119][120][121], including GDM. Highly relevant to the role of redox and Nrf2 in diabetes, cord blood of GDM offspring is associated with the hypermethylation of the Nrf2 stabiliser DJ-1 (PARK7) [122], previously shown to have reduced expression in GDM fetal vascular endothelial cells, potentially contributing towards diminished Nrf2 defenses in the fetal vasculature [101].…”

Targeting on Asymmetric Dimethylarginine-Related Nitric Oxide-Reactive Oxygen Species Imbalance to Reprogram the Development of Hypertension

“…The concept that adult-onset diseases have an early-life origin has been raised, referred to as the developmental origins of health and disease (DOHaD) [2]. Early-life redox imbalance may lead to permanent alterations of function and structure in later life in specific organs that are vulnerable to developing hypertension [3,4]. Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide (NO) synthase inhibitor, can inhibit nitric oxide synthase (NOS) and regulate the NO–reactive oxygen species (ROS) balance [5].…”