Luo ZC, Fraser WD, Julien P, et al. Tracing the origins of ‘fetal origins' of adult diseases: programming by oxidative stress

Department of Obstetrics and Gynecology, University of Ottawa, Ottawa, Ontario, Canada
Medical Hypotheses (Impact Factor: 1.07). 02/2006; 66(1):38-44. DOI: 10.1016/j.mehy.2005.08.020
Source: PubMed


Too small size at birth (due to poor fetal growth and/or preterm delivery) has been associated with substantially elevated risks of the metabolic syndrome (dislipidemia, insulin resistance, hypertension), type 2 diabetes and cardiovascular disease in adulthood. The mechanisms of such "fetal origins" or "programming" of disease phenomenon remain unresolved. Too large size at birth seems also associated with an increased risk. Many known or suspected causes of or conditions associated with adverse (poor or excessive) fetal growth or preterm birth have been associated with oxidative stress. Plausibly, oxidative stress may be a common link underlying the superficial "programming" associations between adverse fetal growth or preterm birth and elevated risks of certain chronic diseases. The mechanisms of oxidative stress programming may be through directly modulating gene expression or indirectly through the effects of certain oxidized molecules. Experimental investigations have well demonstrated the role of redox balance in modulating gene expression, and recent studies indicate that both the insulin functional axis and blood pressure could be sensitive targets to oxidative stress programming. Adverse programming may occur without affecting fetal growth, but more frequently among low birth weight infants merely because they more frequently experienced known or unknown conditions with oxidative insults. As oxidative stress levels are easily modifiable during pregnancy and early postnatal periods (which are plausible critical windows), the hypothesis, if proved valid, will suggest new measures that could be very helpful on fighting the increasing epidemic of the metabolic syndrome, type 2 diabetes and cardiovascular disease. Currently, there are several ongoing large randomized trials of antioxidant supplementation to counter oxidative stress during pregnancy for the prevention of preeclampsia. It would be invaluable if long-term follow-ups of infants born to women in such trials could be realized to test the oxidative stress programming hypothesis in such experimental trial settings.

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    • "Of those, 35 million live in the Andean Mountains, in important cities, such as La Paz, capital of Bolivia (Keyes et al., 2003). This has led to an increased clinical and scientific interest in dissecting the different noxas that induce fetal programming (Luo et al., 2006; Franco et al., 2007; Nuyt, 2008; Schleithoff et al., 2012), but few have focus on the lack of oxygen as a main cause. "
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