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Developmental and behavioral impacts in zebrafish from heavy metal exposure

Lujan, Oscar Ramon (2021) Developmental and behavioral impacts in zebrafish from heavy metal exposure. Masters thesis, Northern Arizona University.

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Arsenic (As) and Uranium (U) are naturally occurring elements found in the earth’s crust with levels varying between locations which can contaminate ground water and impact drinking water sources. The Navajo Nation for example contains unregulated wells that are used daily and may exceed current EPA maximum contaminant levels (MCL) of 10 μg/L As and 30 μg/L U. Translational models such as zebrafish and rats have demonstrated a decrease in kidney tubular function, induction of specific cancers, and an impairment in progeny development after As or U ingestion; however, these experiments generally employ doses that are many folds higher than what is commonly encountered. Furthermore, literature is extensive when investigating As and U effects individually, but research involving As and U in combination and their impact on general human development is limited. A modified fish embryo toxicity test (FET) was utilized to test the hypothesis that low-dose U and As mixture exposure induces negative developmental outcomes. Exposure to U and As mixtures resulted in an increase in movement, decrease in hatching, decreased absorption of the yolk sac, and decreased body malformations. To determine if the outcomes from mixture exposure could be explained by the effects of one of the two chemicals, separate As and U exposures and FET analysis were undertaken. Exposure to U and As individually and in combination resulted in an increase or decrease in movement, and a decrease in hatching, while exposure to U only resulted in an increase in movement and decrease in hatching. All other FET endpoints were unchanged by exposure. Delayed or decreased hatching was a consistent phenotype linked to U exposure, however, cathepsin L activity, an enzyme largely responsible for degrading the chorion to allow for hatching, was not affected following exposure to U. Although movement assessed by FET was reproducibly different in treated embryos compared to controls, the direction of the differences (more or less) was not consistent. While the FET surveyed movement at a single timepoint every 24 hours, a real time analysis leading up to hatching (usually between 48-72 hours post fertilization) showed a clear diminishment in overall movement in U-treated embryos. These results suggest even low-level exposure to uranium can impact motility. Although treatment regimens were limited in these studies, we demonstrated the feasibility of combining the FET, GMS, physiological assays and behavior as a sensitive approach for testing mixture exposure toxicity.

Item Type: Thesis (Masters)
Publisher’s Statement: © Copyright is held by the author. Digital access to this material is made possible by the Cline Library, Northern Arizona University. Further transmission, reproduction or presentation of protected items is prohibited except with permission of the author.
Keywords: Arsenic; Uranium; Heavy metal exposure; Zebrafish; Water pollution; Wells
Subjects: R Medicine > RB Pathology
MeSH Subjects: D Chemicals and Drugs > D01 Inorganic Chemicals
NAU Depositing Author Academic Status: Student
Department/Unit: Graduate College > Theses and Dissertations
College of the Environment, Forestry, and Natural Sciences > Biological Sciences
Date Deposited: 03 Feb 2022 18:59
Last Modified: 03 Feb 2022 18:59
URI: https://openknowledge.nau.edu/id/eprint/5643

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