Does abnormal one-carbon metabolism or hyperglycaemia in utero cause epigenetic change and fetal programming of cardiome

糖尿病和心血管疾病（“心脏代谢”疾病）在世界范围内变得越来越普遍。患这些疾病的风险与基因遗传和人的环境有关。环境的影响在怀孕期间尤为重要，对营养不良和糖尿病母亲的研究表明，她们的孩子患心脏代谢疾病的风险增加。这种疾病在胎儿发育过程中被“编程”的想法已经在人群和动物实验中进行了研究，但其发生的机制尚不清楚。在这方面，表观遗传学领域正在为这种编程如何发生提供令人兴奋的见解。它描述了环境触发因素如何通过 DNA 结构周围的一系列化学反应影响基因的开启或关闭。这项研究将探讨母亲的高血糖水平和营养不良如何导致表观遗传变化，从而使后代面临心脏代谢疾病的风险。这项研究将在小鼠和人类身上进行，以确定这些变化是否可以代代相传。将使用涉及实验室实验和计算机数学分析的新技术来回答这些问题。

Diabetes and cardiovascular disease (the ‘cardiometabolic‘ diseases) are becoming increasingly common throughout the world. The risk of developing these diseases relates to both genetic inheritance and a person‘s environment. The effects of environment are particularly important during pregnancy, and studies of malnourished and diabetic mothers show an increased risk of cardiometabolic disease in their children. This idea of disease being ‘programmed‘ during fetal development has been studied across populations and in animal experiments, but the mechanisms through which it occurs are not understood. In this respect, the field of epigenetics is providing an exciting insight into how this programming might occur. It describes how environmental triggers can affect how genes are switched on or off via a sequence of chemical reactions around the structure of DNA. This study will look at how high blood glucose levels and poor nutrition in mothers could cause epigenetic changes that put offspring at risk of cardiometabolic disease. The study will be done in mice as well as humans to identify whether these changes can be inherited through generations. New techniques involving both laboratory experiments and computerised mathematical analysis will be used to answer these questions.