Date of Graduation
Master of Science, Biology
congenital heart defects, mouse embryo, heart development, hemodynamic force, hemodynamic loading, embryo culture
The most common type of birth defects are congenital heart defects (or CHDs). Though a few cases of CHDs have been attributed to genetic defects specific to the heart, substance exposure, or to maternal disease, the cause of most CHDs is unknown. Thus, further research is needed to determine how CHDs form. Very few studies have investigated how physiological factors like perturbations of blood flow can affect normal heart development. For instance, increasing or decreasing the resistance to blood flow can alter development of the heart in both zebrafish and chicken embryos. This could be one mechanism to explain CHD formation, but further investigation in a mammalian system is needed. To examine this idea, I experimentally manipulated cultured mouse embryos, testing the effects of decreased blood viscosity (to create low hemodynamic force [cardiovascular system] or low hemodynamic loading [heart-specific]). To determine the effects on heart development, I prepared the embryos for 3D imaging by optical projection tomography (OPT), and assessed heart volume and myocardial thickness. There was no detectable change in the volume of hearts under low hemodynamic force compared to hearts with normal hemodynamic force. However, I did observe a decrease of myocardial thickness in hearts with low hemodynamic force compared to control hearts. Thus, this study demonstrates that even at very early stages of embryonic development, alterations in blood flow can influence heart development. This indicates CHD formation can be exacerbated upon initial exposure to a primary cause (genetic defects, substance exposure or maternal disease) due to changes in hemodynamic forces.
© Samantha Jean Fredrickson
Fredrickson, Samantha Jean, "The Role of Hemodynamic Force on Development of the Mouse Embryonic Heart" (2017). MSU Graduate Theses. 3122.