Diabetes at the heart of the matter
The 'Molecular mechanisms in diabetic embryopathy' (Diabetic embryopathy) project is studying how an embryo can be affected if its mother has diabetes. Evidence already points to an increased risk for abnormal heart development and functioning. Although actual malformations are well documented, there is still very little understanding about the molecular causes at play. With the main goal of determining what is happening at the level of tissues or cell types in embryos exposed to diabetes, team members aim to identify the molecular processes leading to cardiovascular malformations brought on by diabetes. The primary hypothesis is that during a diabetic pregnancy, gene expression is altered in such a way that normal heart development is disrupted. Using a mouse model, Diabetic embryopathy analysed changes that came about in a developing embryonic heart when placed in a diabetic environment. These embryos had 17% more abnormal heart formations compared to unexposed embryos. Cardiovascular defects were noted in the form of haemorrhages and oedema as well as in the organ's structure. Global gene expression profiling confirmed that interruptions in the regular transfer of genes play a major role in embryo development. One of these transcription factors is hypoxia-inducible factor 1 alpha (HIF1a). Study results revealed a 20% increase in congenital defects and significant changes in the gene expression of HIf1a+/- embryos when exposed to diabetes. This points to HIF1-activated pathways as possible key mechanisms in development of birth defects brought on by exposure to diabetes. The results of some of the project's studies have been presented at the 49th Annual Meeting of the Teratology Society (2009), twice in the Journal of Applied Physiology (2010), and as a poster at Keystone, Colorado, US (2010). Diabetic embryopathy is working to enhance current knowledge of developmental disorders associated with diabetic pregnancies. This will also facilitate better understanding of adult diseases related to diabetes.
