Keap1-Nrf2 regulated redox signaling in utero: Priming of disease susceptibility in offspring.
Intrauterine exposure to gestational diabetes, pre-eclampsia or intrauterine growth restriction alters the redox status of the developing fetus. Such pregnancy-related diseases in most cases do not have a readily identifiable genetic cause, and epigenetic 'priming' mechanisms in utero may predispose both mother and child to later-life onset of cardiovascular and metabolic diseases. The concept of 'fetal programing' or 'developmental priming' and its association with an increased risk of disease in childhood or adulthood has been reviewed extensively. This review focuses on adaptive changes in the in utero redox environment during normal pregnancy and the consequences of alterations in redox control associated with pregnancies characterized by oxidative stress. We evaluate the evidence that the Keap1-Nrf2 pathway is important for protecting the fetus against adverse conditions in utero and may itself be subject to epigenetic priming, potentially contributing to an increased risk of vascular disease and insulin resistance in later life.
Cardiovascular Division, British Heart Foundation of Research Excellence, Faculty of Life Sciences & Medicine, King's College London, 150 Stamford Street, London SE1 9NH, UK.
Sarah J
SJ
Chapple
Cardiovascular Division, British Heart Foundation of Research Excellence, Faculty of Life Sciences & Medicine, King's College London, 150 Stamford Street, London SE1 9NH, UK.
William M
WM
Puszyk
Cardiovascular Division, British Heart Foundation of Research Excellence, Faculty of Life Sciences & Medicine, King's College London, 150 Stamford Street, London SE1 9NH, UK. Electronic address: giovanni.mann@kcl.ac.uk.
Giovanni E
GE
Mann
D000818:Animals; D016640:Diabetes, Gestational; D004198:Disease Susceptibility / Q000378:metabolism*; D005260:Female; D047109:Fetal Development / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D047908:Intracellular Signaling Peptides and Proteins; D051267:NF-E2-Related Factor 2
Cardiovascular disease; Developmental priming; Epigenetics; Fetal endothelial cells; Fetal programing; Gestational diabetes; Intrauterine growth restriction; Keap1–Nrf2; Pre-eclampsia; Redox signaling; Type 2 diabetes