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ORCID

https://orcid.org/0000-0002-4672-515X

Access Type

Campus-Only Access for Five (5) Years

Document Type

thesis

Degree Program

Public Health

Degree Type

Master of Science (M.S.)

Year Degree Awarded

2022

Month Degree Awarded

May

Abstract

Estrogenic chemicals are common pollutants in wastewater and current methods used in wastewater treatment processes are not typically effective in removing these compounds. Thus, many estrogenic chemicals, as well as other pharmaceuticals, are detected in drinking water supplies, contributing to human exposures. This concerning public health situation has led some green chemists to investigate the feasibility and efficacy of tetra-amido macrocyclic ligands (TAML), which have been proposed to be environmentally friendly catalysts that can be used to treat wastewater. TAML works by catalyzing the oxidation of micropollutants, breaking pollutants down into substances that can be assimilated by bacteria. These breakdown products are anticipated to no longer pose an environmental or health concern. Prior to their use in environmental matrices, TAML must first be evaluated to ensure that these compounds pose a low environmental and human-health hazard. Here, we exposed adult female mice to one of three doses of New-TAML 7 (NT7), or an estrogen receptor agonist (ethinyl estradiol, EE2) or an androgen receptor antagonist (flutamide), for two weeks prior to mating, throughout pregnancy, and throughout the lactational period. Male mice used for breeding purposes, the F0 males, were also exposed to the drinking water during the 2-week mating period. Following this acute exposure, the F0 males were necropsied and evaluated for signs of overt toxicity and repro-endocrine disruption. There was a statistically significant decrease in the F0 males spleen weight. Male offspring, the F1 generation, were evaluated at weaning (postnatal day 21), in puberty (postnatal day 32), and in adulthood. We first evaluated organs known to be sensitive to toxic effects. In male mice developmentally exposed, we have discovered that all treatments decreased spleen size at postnatal day (PND) 21 but not in early adulthood. At PND 16, no significant effects were observed. At PND21, no effects were observed on the weight of the kidney, liver, testes, or seminal vesicles; however, spleen weight was significantly decreased in the positive controls and the mid-NT7 group. In early adulthood, no effects have been observed on organ weights of the flutamide group; however, the size of both testes is significantly affected by the mid-NT7 dose and the EE2 treatment. By six months of age, there were no statistically significant effects, although this is likely in part due to inadequate statistical power. We also evaluated the effect of NT7, EE2, and flutamide on the male mouse mammary gland. Because of the conserved role hormones play in mouse development, a mammary gland is a valuable tool for identifying endocrine disruptors. We found that EE2 increased the size and number of branching points starting at PND21 and continuing until nine weeks of age. TAML had little effect on the morphology of the male mammary gland, with the exception of increased ductal branching at PND21. This, along with the change in testes weight, may suggest TAML can affect estrogen-mediated outcomes; many of our observed effects warrant additional study.

DOI

https://doi.org/10.7275/28633629

First Advisor

Laura N. Vandenberg

Second Advisor

Alicia R. Timme-Laragy

Third Advisor

Carrie J. Nobles

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