Epigenetic processes in transmission of prenatally-induced phenotypes between generations

怀孕期间营养不良的母亲所生的婴儿成年后患心脏病、中风、高血压、2型糖尿病和肥胖症的风险增加。有新的证据表明，怀孕期间这种营养不良的后果可能会传给孙辈，即使他们的女儿在怀孕期间有足够的营养。这些影响在怀孕期间喂食蛋白质含量减少的大鼠的后代中得到了复制。我们已经确定了一种机制，通过这种机制，怀孕期间的营养不良可能会导致胎儿基因控制方式的改变，并导致下一代患病风险增加。这种基因控制的过程被称为表观遗传学。在这个项目中，我们将使用大鼠模型来研究母亲的饮食改变下三代后代基因的表观遗传控制的机制。我们已经有证据表明，这涉及到第一代中的一种称为DNA甲基转移酶-1的酶，现在我们需要确定这种酶是否涉及到后代。我们还表明，在母亲的饮食中添加叶酸可以防止第一代基因的表观遗传控制发生变化。我们将研究叶酸是否可以防止连续几代表观遗传控制的变化。

Babies born to mothers who have poor nutrition during pregnancy have an increased risk of heart attack, stroke, high blood pressure, type 2 diabetes mellitus and obesity when they become adults. There is emerging evidence that the consequences of such nutrition during pregnancy can be passed to grandchildren even when their daughters have adequate nutrition during pregnancy. These effects have been replicated in the offspring of rats fed a diet with reduced protein content during pregnancy. We have identified a mechanism by which poor nutrition during pregnancy can result in changes to how genes are controlled in the fetus and give which result in increased risk of disease in a future generation. This process of gene control is called epigenetics. In this project we will use the rat model to investigate the mechanism by which the diet of the mother changes the epigenetic control of genes in the next three generations of offspring. We already have evidence that this involves an enzyme called DNA methyltransferase-1 in the first generation and now we need to determine whether this enzyme is involved in subsequent generations. We have also shown adding folic acid to the mother's diet prevents changes in the epigenetic control of genes in the first generations. We will investigate whether folic acid can prevent changes in epigenetic control in successive generations.