Pharmacology, Toxicology and Environmental Health Commons^™

Exposure To Endocrine Disrupting Chemicals And The Effects On Inflammation And Mammary Tumor Progression, Stephanie Morin

Doctoral Dissertations

The vast majority of breast cancers, ~70%, are not directly related to an inherited genetic mutation. Environmental factors play a dominant role in the etiology of most breast cancers. There is a subset of chemicals that are able to affect the homeostasis of hormones called endocrine disrupting chemicals (EDCs). Many of these chemicals are pervasive and persistent making the chances for lifetime exposure more prevalent. While many of these chemicals have been deemed safe, a subset of them have come under review to reassess their safety. As estrogen is critical for breast development and can act as a mitogen in …

Developmental Exposures To Pfas Mixtures Impair Elongation Of The Exocrine Pancreas In Zebrafish (Danio Rerio), Emily M. Formato

Masters Theses

Poly- and perfluoroalkyl substances (PFAS) are a class of bioaccumulative toxicants used in numerous industrial and commercial products. Perfluorooctanesulfonic acid (PFOS) alters pancreatic organogenesis during development, and perfluorohexanesulfonic acid (PFHxS) has been suggested as a replacement for PFOS due to its shorter carbon chain, but they are often found together in surfactants, such as legacy aqueous film-forming foam. This study investigates how developmental exposures to a PFAS mixture (PFHxS + PFOS) impact the developing exocrine pancreas. Zebrafish embryos (Tg(ptf1a:GFP)) were exposed to 0.01% DMSO, or 8, 16, 32 μM PFHxS alone, 16 μM PFOS alone, and 8, 16, and 32 …

Activation Of Nrf2 At Critical Windows Of Development Alters Protein S-Glutathionylation In The Zebrafish Embryo (Danio Rerio), Emily G. Severance

Masters Theses

Perturbation of cellular redox homeostasis to a more oxidized state has been linked to adverse human health effects such as diabetes and cancer. However, the impact of altering the regulation of redox homeostasis during development is not fully understood. Specifically, this project investigates the role of the Nrf2 antioxidant response pathway and its effect on glutathione (GSH; cellular redox buffer) at critical windows of development. To explore this, we used zebrafish embryos (Danio rerio) as a model due to the function of GSH and the Nrf2 being conserved among vertebrates. We exposed zebrafish embryos to three Nrf2 activators: two antioxidant …

Investigating The Developmental Impacts Of 3,3’-Dichlorobiphenyl (Pcb-11) In Zebrafish (Danio Rerio), Monika A. Roy

Doctoral Dissertations

The environmental pollutant 3,3’-dichlorobiphenyl (PCB-11) is a lower-chlorinated polychlorinated biphenyl (PCB) congener present in air and water samples. Both PCB-11 and its metabolite, 4-PCB-11-Sulfate, are detected in humans, including in pregnant women. The work conducted for this dissertation takes a developmental toxicology approach and uses zebrafish (Danio rerio) to investigate PCB-11’s potential impacts to the liver and pancreas. Chapter 1 introduces PCBs and the current knowledge gaps. Chapter 2 investigates PCB-11 interactions in short-term 4-day exposures with the Aryl hydrocarbon receptor (Ahr) pathway in both 0-20 mM individual and mixture exposures with other Ahr agonists. In Chapter 3, …

Redox Signaling In The Zebrafish Embryo And Implications For Endocrine Pancreas Morphogenesis, Archit Rastogi

Doctoral Dissertations

The glutathione (GSH) system evolved to combat oxygen toxicity in nearly all living organisms, and serves as the predominant cellular redox buffer in vertebrates. This dissertation explores the roles of GSH during embryogenesis using the zebrafish (Danio rerio). The first agnostic in vivo characterization of GSH utilization in the embryo revealed strict spatiotemporal GSH profiles in developing organ systems. Interruption of these GSH profiles by exogenous xenobiotics led to organ specific adverse developmental outcomes; pancreatic β-cells were found to be especially susceptible and developed atypical morphologies following redox active xenobiotic exposures. Pancreatic β-cells lacked expression of Nrf2a (Nuclear …

Environmental Risk Factors For Inflammatory Bowel Disease: Triclosan And Other Consumer Antimicrobials, Katherine Z. Sanidad

Doctoral Dissertations

Inflammatory bowel disease (IBD) has become a serious health problem since the incidence and prevalence of IBD has dramatically increased throughout the world. There is evidence that environmental factors are primarily responsible for the increase of IBD, therefore, it is important to identify novel environmental risk factors to reduce the risk of IBD and its associated diseases. Antimicrobials used in consumer products might serve as environmental risk factors for IBD and its associated diseases. Triclosan (TCS), triclocarban (TCC), benzalkonium chloride (BAC), benzethonium chloride (BET), and chloroxylenol (PCMX) are widely used antimicrobial ingredients in consumer products and are ubiquitous contaminants in …

Developmental Exposure To Xenoestrogens: Effects On The Mouse Mammary Gland Development And Response To Estrogen, Durga Kolla

Masters Theses

Humans experience ubiquitous exposures to estrogenic environmental chemicals from food, personal care products, and other industrial and consumer goods. Bisphenol A (BPA), a well-studied xenoestrogen, is known to alter development of estrogen-sensitive organs including the brain, reproductive tract, and mammary gland. Bisphenol S (BPS), which has a similar chemical structure to BPA, is also used in many consumer products, but its effects on estrogen-sensitive organs in mammals has not been thoroughly examined. In our study, pregnant CD-1 mice were orally exposed to BPS or ethinyl estradiol (EE2, a positive control for estrogenicity) from gestational day 9 through postnatal day (PND) …

Evaluating A Novel Photochemical Tool For Labeling And Tracking Live, Endogenous Calcium-Permeable Ampars, Rosamund Elizabeth Combs-Bachmann

Masters Theses

The purpose of this research is to advance development of a photochemical tool designed to probe the role of ionotropic glutamate receptor signaling in neurodegenerative processes, and to delve more deeply into the biological processes underlying the role of these receptors in signaling and memory formation. This ligand-targeted nanoprobe was designed and developed in our lab to label endogenous calcium-permeable AMPARs (CP-AMPARs) in live cells with minimal disruption to native receptor activity. Nanoprobe is designed to use naphthyl acetyl spermine (NASPM) as a photocleavable ligand to target and covalently label native CP-AMPARs with a non-perturbing, fluorescent marker that then allows …

Effects Of Developmental Exposures Of Two Emerging Environmental Toxicants On Estrogen-Sensitive Endpoints, Corinne E. Hill

Masters Theses

Thousands of synthetic chemicals have been released into the environment, causing widespread exposures of wildlife and humans alike. Some of these chemicals are known to disrupt aspects of hormone action thus inducing abnormalities in endocrine tissues and organs. Bisphenol S (BPS) and tetrabromobisphenol A (TBBPA), two largely unstudied chemicals commonly used in consumer products, are suspected to have endocrine disrupting properties based on their similar chemical structures to known endocrine disrupting chemicals (EDCs). To determine whether developmental exposure to BPS or TBBPA induced abnormalities in the ovary, mice were administered oil, BPS or TBBPA during pregnancy and lactation. The ovaries …

Rapid Method Of Processing Sperm For Nucleic Acid Extraction In Clinical Research, Matthew K. De Gannes

Masters Theses

Background: Sperm contain highly compact nuclei, inhibiting DNA extraction using traditional techniques. Current methods extracting sperm DNA involve lengthy lysis and no means of stabilizing DNA, hindering clinical research.

Objective: We sought to optimize an efficient method of extracting high quality human sperm DNA.

Methods: Sperm from three volunteers were isolated using PureCeption. We tested 1) proteinase K with DNA/RNA Shield, 2) DTT and TCEP as reducing agents, 3) QIAshredder homogenization, and 4) stability of sperm DNA fresh (baseline) or after 4 weeks of storage at 4^OC in DNA/RNA Shield using modified Quick-gDNA MiniPrep. DNA was PCR amplified …