| Popis: |
Fetal programming is a well-established phenomenon in which suboptimal maternal nutrition during gestation ‘programs’ offspring to have an increased predisposition to metabolic disease in adulthood. The mechanism underlying fetal programming remains unknown; however, many researchers have proposed that epigenetics may play a significant role. Epigenetic markers of gene activity and silence are established early on in embryonic development, after which they are faithfully inherited and stably maintained in all cells of an organism. The epigenetic programming hypothesis therefore proposes that perturbed maternal nutrition during gestation may effect epigenetic changes in the fetus that are maintained into adulthood and predispose to late-onset disease. There has only been limited evidence for this hypothesis so far, however. The aim of my study was to use mouse models to investigate whether epigenetic changes occur in offspring exposed to three different maternal dietary modifications: maternal methyl donor supplementation, maternal overnutrition and maternal undernutrition. A microarray methylation analysis strategy was chosen to allow thorough characterization of global methylation changes in offspring. The results of this study show that offspring exposed to changes in maternal nutrition exhibit small and subtle methylation changes throughout the genome that can affect overall methylation variability. These changes primarily occur in genes involved in development and gene expression and may contribute to the phenotypic changes that occur in fetal programming. More epigenetic changes were also found to occur with multiple generations of exposure, suggesting that epigenetic programming may provide a means of adaptive evolution in response to long-term nutritional challenges. |
