Abstract

Biomimetic properties of endocrine disrupting compounds (EDC) enable these chemicals to induce physiological responses in organisms at the cellular level, affecting fishes, amphibians, reptiles, birds, and mammals. Perchlorate is a ubiquitous EDC to which nearly all humans of industrialized countries are exposed. Perchlorate competitively inhibits the sodium-iodide symporters located within the follicular cells of the thyroid gland, reducing the body’s ability to uptake iodide and synthesize thyroid hormone (TH), a crucial hormone in the regulation of many metabolic processes. Threespine stickleback (Gasterosteus aculeatus) and zebrafish (Danio rerio) are aquatic model organisms used in perchlorate exposure research. Exposure causes many common shared pathologies; however, sex and species-specific results have been observed between the two models, implying the potential for variation in results across other species as well. These models provide much insight into the effects of perchlorate exposure, but mammalian models such as mice (Mus musculus) provide a better representation of the effects of perchlorate exposure in humans across all developmental stages. For this project, I aimed to determine the effects of perchlorate exposure on swimming performance in adult wildtype zebrafish and multi-system organ development in sexually mature C57/BL6 mice. Zebrafish embryos were exposed beginning at ~2 hours post-fertilization to either a 0 ppm (control), 10 ppb, 10 ppm, or 100 ppm perchlorate solution until 100-114 days post-fertilization and subject to a standard Ucrit test to assess swimming performance. Mice were exposed for 49 days after weaning, euthanized, and organs including the thyroid gland, liver, testes, and ovaries were dissected, sectioned, and stained using hematoxylin and eosin. Interestingly, the Ucrit of perchlorate exposed zebrafish did not differ from that of the control group; however, the ability to acclimate to low flow showed a dose-dependent decline in the number of fish able to complete acclimation as exposure concentration increased. Morphological abnormalities found within the mouse thyroid included a reduction in follicle area, and an increase in lipid deposition and blood vessel frequency. Perchlorate exposure caused an increase in the aggregates of inflammatory cells in exposed livers, suggesting that perchlorate exposure causes insult to hepatic tissue. Within reproductive tissues, perchlorate caused an increase in vacuolation and disorganization in testis and increased the number of follicles in the exposed ovaries. These data support the need for more research on perchlorate exposure as mice display similar and disparate effects to the established aquatic models.

Advisor

Michael Minicozzi

Committee Member

Rachel Cohen

Committee Member

Frank von Hippel

Date of Degree

2022

Language

english

Document Type

Thesis

Degree

Master of Science (MS)

Program of Study

Biology

Department

Biological Sciences

College

Science, Engineering and Technology

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Rights Statement

In Copyright