000007535 001__ 7535 000007535 005__ 20231129124938.0 000007535 0247_ $$2DOI$$a10.6083/2b88qc733 000007535 037__ $$aETD 000007535 245__ $$aA multi-modal investigation of the developmental origins of congenital heart defects in avian embryos 000007535 260__ $$bOregon Health and Science University 000007535 269__ $$a2019 000007535 336__ $$aThesis 000007535 502__ $$bM.S. 000007535 520__ $$aMaternal conditions that disrupt the normal embryonic environment during heart development can lead to structural defects in the heart, ultimately compromising the heart's function and leading to increased morbidity and mortality. Avian models of cardiovascular development have played a key role in elucidating the mechanisms by which congenital heart defects form during critical periods of early heart development. However, current avian models are restricted to narrow developmental windows, thereby limiting one's ability to study the manifestation of cardiac defects over a larger, more complete timescale. The work presented in this thesis uses novel techniques in an avian model coupled with multiscale imaging modalities to study how transient interventions during early heart formation affect the overall development of the heart. Specifically, we employ a combination of 3D electron microscopy, light microscopy, and micro-computed tomography to understand how pharmacological or surgical interventions performed during tubular heart stages affect both early- and late-stages of cardiac development. Overall, our studies revealed unreported cardiac malformation phenotypes in response to early interventions as well as accompanying ultrastructural changes in cardiac tissues. Furthermore, the models and methods presented here provide a framework for a comprehensive multiscale developmental analysis that can potentially be applied to other organs in the chick, and adapted for use in other small animal models. 000007535 650__ $$aPhenotype$$023948 000007535 650__ $$aAnimals$$014770 000007535 650__ $$aHeart$$019927 000007535 6531_ $$aelectron microscopy 000007535 6531_ $$aanimal models 000007535 6531_ $$acongenital heart defects 000007535 691__ $$aSchool of Medicine$$041369 000007535 692__ $$aDepartment of Biomedical Engineering$$041397 000007535 7001_ $$aRykiel, Graham S. 000007535 8564_ $$9f0eb3ceb-9a84-4fe2-a94e-50f3c9cd77cb$$s4438367$$uhttps://digitalcollections.ohsu.edu/record/7535/files/rykiel.graham.2019.pdf 000007535 905__ $$a/rest/prod/2b/88/qc/73/2b88qc733 000007535 909CO $$ooai:digitalcollections.ohsu.edu:7535$$pstudent-work 000007535 980__ $$aTheses and Dissertations