Abstract

Neural tube defects (NTDs) are the second most common type of congenital birth defect that affect infants worldwide. There are several proposed mechanisms for NTDs, but no definitive mechanism has yet been described. One possible mechanism is oxidative disruption of normal developmental signaling. The purpose of this study is to culture whole mouse embryos with three common developmental toxicants, mono-2-ethylhexyl phthalate (MEHP, a plastic pollutant), Fumonisin B1 (FB1, a corn mold), and valproic acid (VPA, an anticonvulsant drug), all of which are known to cause NTDs, and compare their shifts in redox potential and changes to important signaling pathways through transcriptomic analysis. To determine if prevention of oxidative stress decreases the likelihood of developing an NTD, preventative measures were taken by pretreating pregnant dams with 3H-1,2-dithiole-3-thione (D3T), an effective nuclear factor erythroid 2-related factor 2 (NRF2) inducer. It was found that between the three chemicals, two genes were significantly dysregulated, Makorin-2 (MKRN2) and Microtubule Associated Protein-6 (MAP6), both of which are implicated in NTDs. After staining embryos with lysotracker red (for apoptosis) or DCP-Rho1 (for oxidative stress), it was found that D3T pretreatment generally lowers the amount of apoptosis and oxidative stress in toxicant treated embryos. However, it only decreased the prevalence of NTDs seen in embryos cultured with FB1 or VPA. These results demonstrate common mechanisms that are potentially related in the formation of NTD and will help to target possible preventative measures.

Degree

MS

College and Department

Life Sciences; Physiology and Developmental Biology

Rights

https://lib.byu.edu/about/copyright/

Date Submitted

2024-06-04

Document Type

Thesis

Handle

http://hdl.lib.byu.edu/1877/etd13252

Keywords

neural tube defects, oxidative stress, MEHP, FB1, VPA, D3T, NRF2

Language

english

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