ABSTRACT
Epidemiological studies reveal that prenatal adverse environment could cause lower birthweight in offspring and increase the susceptibility to multiple chronic diseases (e.g. metabolic and neuropsychiatric diseases etc.) after maturity. However, the underlying mechanism remains unclarified. The hypothalamic-pituitary-adrenal (HPA) axis is a key neuroendocrine axis playing pivotal roles in systemic stress responses before and after birth. It is also an important but vulnerable fetal targeting organ. Previous studies showed that many environmental insults during pregnancy, including external environment and maternal health condition, could affect fetal development in multi-ways via maternal-placental-fetal unit, which leads to the intrauterine programming alteration of HPA axis and the in?creased susceptibility to chronic diseases in adulthood. This article reviews the latest global advances in the etiology of increased susceptibility to adult diseases induced by compromised prenatal environ?ment and the associated intrauterine programming mechanisms by incorporating our recent research findings, and proposes that the fetal over-exposure to maternal glucocorticoids (GC) could bring about the intrauterine neuroendocrine metabolic programming alteration in offspring:the core is the program?ming of GC-insulin-like growth factor 1 axis in multiple organs, and the abnormal epigenetic modification is involved in this programming.
ABSTRACT
La evidencia indica que la exposición a diversas condiciones ambientales en etapas tempranas de la vida puede inducir alteraciones persistentes en el epigenoma. Los estudios epigenómicos en sujetos obesos han permitido evaluar el papel de los mecanismos epigenéticos en el origen y desarrollo de la obesidad. La presente revisión aborda estudios que dan cuenta de la asociación entre la obesidad y metilación global del genoma (ADN), analizando el potencial impacto de intervenciones previas y posteriores al nacimiento que afectan la metilación del ADN y la obesidad en etapas más avanzadas de la vida. Estudios realizados principalmente en leucocitos, han logrado identificar sitios del ADN diferencialmente metilados asociados con obesidad. Estudios hasta la fecha no han demostrado que dichos cambios en metilación sean revertidos luego de bajar de peso. Esto contrasta con resultados iniciales en este campo, que sugieren que existirían marcadores epigenéticos presentes desde el nacimiento que permitirían definir el riesgo de obesidad durante el curso de la vida. La evidencia actual sugiere que algunas marcas epigenéticas son modificables, basándonos en la exposición en la vida intrauterina y también por los hábitos dietarios y de actividad fisica durante las etapas del crecimiento y en la adultez. Esto sugiere que existe la oportunidad de intervenir durante la gestación o en la vida posnatal temprana, que modificaría los perfiles epigenéticos desfavorables e idealmente contribuiría a prevenir la obesidad en los sujetos o poblaciones susceptibles.
Current evidence supports the notion that exposure to various environmental conditions in early life may induce permanent changes in the epigenome that persist throughout the life-course. This article focuses on early changes associated with obesity in adult life. A review is presented on the factors that induce changes in whole genome (DNA) methylation in early life that are associated with adult onset obesity and related disorders. In contrast, reversal of epigenetic changes associated with weight loss in obese subjects has not been demonstrated. This contrasts with well-established associations found between obesity related DNA methylation patterns at birth and adult onset obesity and diabetes. Epigenetic markers may serve to screen indivuals at risk for obesity and assess the effects of interventions in early life that may delay or prevent obesity in early life. This might contribute to lower the obesity-related burden of death and disability at the population level. The available evidence indicates that epigenetic marks are in fact modifiable, based on modifications in the intrauterine environment and changes in food intake, physical activity and dietary patterns patterns during pregnancy and early years of adult life. This offers the opportunity to intervene before conception, during pregnancy, infancy, childhood, and also in later life. There must be documentation on the best preventive actions in terms of diet and physical activity that will modify or revert the adverse epigenetic markers, thus preventing obesity and diabetes in suceptible individuals and populations.