Embryonic Exposure to Sodium Perchlorate Disrupts Organ Development in Mice

Abstract

Perchlorate is an endocrine disrupting compound (EDC) commonly used for its oxidative properties. Perchlorate has been detected in many industrialized countries in drinking water, soil, foods, and breast milk. Perchlorate competitively inhibits the uptake of iodide into the thyroid follicles via the sodium/iodide symporter (NIS), thus reducing thyroid hormone synthesis. Perchlorate has many conflicting results in the toxicological effects that perchlorate has on organ development in model fishes, but much less work has been done on mammals. In the present study, I examined the morphological effects of environmentally relevant concentrations (0, 10, and 100ppm) of sodium perchlorate on the thyroid, liver, kidneys, testes and ovaries. Sexually mature female mice were randomly divided into the three treatment groups, bred, and exposed to perchlorate via water until offspring were weaned at postnatal day 36 (P36). Offspring continued exposure for 49 days at the same concentration as their mother, euthanized at P85, whole body perfused with 4% paraformaldehyde in PBS, and the target organs were dissected, sectioned, and stained using hematoxylin and eosin. Perchlorate exposed mice displayed a significant decrease in colloid area with significantly increased follicle frequency and angiogenesis within the thyroid. Within the liver, I found a significant increase in the presence of ballooned hepatocytes and lipid accumulation, key morphological characteristics in diagnosing nonalcoholic fatty liver disease (NAFLD). Within the kidney, I found perchlorate significantly altered nephron tubule thickness. In the testes, perchlorate exposure caused an increase in disorganized seminiferous tubules and a non-monotonic increase in Leydig cell nuclei area within the 10ppm group. 10ppm and 100ppm exposed mice showed an increase in blood vessel size within the testes. The present results compared to previous studies suggest that perchlorate may have different effects on organ development based on early or late-stage developmental exposure.

Advisor

Michael Minicozzi

Committee Member

Rachel Cohen

Committee Member

Frank von Hippel

Date of Degree

2024

Language

english

Document Type

Thesis

Program of Study

Biology

Department

Biological Sciences

College

Science, Engineering and Technology

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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