Abstract
One of the first embryonic structures generated during early human development is the neural tube. The embryonic process of neurulation, including neural tube closure, is necessary for proper brain and spinal cord development, whereas improper closure leads to neural tube defects including anencephaly, spina bifida, and craniorachischisis. The mechanism by which these defects occur is unknown, but some evidence suggest that redox disruption may play a role. Cellular redox state is important in regulating key processes during neural tube closure, including differentiation, proliferation, gene expression, and apoptosis. This study aims to determine whether redox potential shifts and these key processes are affected similarly or differentially after treatment with three neural tube defect-inducing developmental toxicants: ceramide (C2), valproic acid (VPA), and fumonisin (FB1). Using the P19 cell model of neurogenesis, in both undifferentiated and terminally differentiated cells, we analyzed glutathione (GSH) redox (Eh) potential to evaluate the effect of each toxicant over time. We show that in C2 and VPA treated cultures an oxidizing shift occurs, but interestingly, FB1 treatment results in a reducing shift in embryonic GSH Eh as compared to untreated cultures. Using the chick embryo model, comparable redox shifts were observed as were seen in P19 cells, supporting similarity between the models. To better understand how differential shifts in the redox state can result in similar defects, we then examined potential variances in neuronal differentiation and cellular proliferation, survival, metabolism, adhesion, and gene expression under each treatment. We report changes to cellular and embryonic endpoints that support dysmorphogenesis, likely the result of oxidizing or reducing stress that altered redox state. These results support the need for broad comparative analyses such as this to determine whether toxicants that cause the same types of defects, whether NTDs or others, act through similar or different mechanisms. This can better inform preventative measures used to reduce the risk and occurrence of birth defects.
Degree
PhD
College and Department
Life Sciences; Physiology and Developmental Biology
Rights
https://lib.byu.edu/about/copyright/
BYU ScholarsArchive Citation
Ross, Micah Marie, "A Comprehensive Comparison of Teratogenic Compounds Known to Induce Neural Tube Defects in the Chicken Embryo" (2020). Theses and Dissertations. 9257.
https://scholarsarchive.byu.edu/etd/9257
Date Submitted
2020-07-31
Document Type
Dissertation
Handle
http://hdl.lib.byu.edu/1877/etd11895
Keywords
ceramide, fumonisin b1, valproic acid, neural tube defects, teratogen, maternal obesity, birth defects, oxidative stress, chicken embryo
Language
english