Environmental influences on mouse embryonic development

Environmental influences on mouse embryonic development

Speaker: Dr Duncan Sparrow, Department of Physiology, Anatomy and Genetics, University of Oxford

Host: Malcolm Logan

Abstract:

The heart is the first organ to form in the mammalian embryo. The process is very complex, requiring cells derived from at least four distinct progenitor populations, an elaborate transcription factor network, and the integration of many different signalling pathways. A failure of any of these individual elements can result in a variety of types of heart defects. In humans, such heart defects are called congenital heart disease (CHD), and this is the most common type of human birth defect, being present in ~1% of live births and ~10% of still-births worldwide. However, despite intensive investigation by modern genomics and the discovery of over 100 genes associated with CHD, only about 30% of cases can be explained genetically. This is because CHD can also be caused by non-genetic factors, for example by environmental stresses during pregnancy. Such factors include maternal conditions and diseases like viral infection and hyperthermia, folate deficiency, maternal diabetes and phenylketonuria. In addition, maternal exposures to pharmaceuticals such as anti-convulsant and anti-arrhythmia ion-channel blockers have also been associated with increased CHD risk. However, despite these factors being known for many decades, virtually nothing is known of how they cause CHD. We have developed mouse models of several environmental factors, and are using a combination of 3D morphological imaging and molecular analysis to understand how these factors perturb embryonic heart formation.