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ORCID

https://orcid.org/0000-0001-5891-2561

Access Type

Open Access Thesis

Document Type

thesis

Degree Program

Molecular & Cellular Biology

Degree Type

Master of Science (M.S.)

Year Degree Awarded

2022

Month Degree Awarded

September

Abstract

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 μM PFHxS plus 16 μM PFOS. Embryos underwent refreshing exposures (3 hours post fertilization (hpf) - 96 hpf) or static exposures (3, 24, 48, or 72 hpf - 96 hpf) and then live imaging to quantify the truncated exocrine pancreas phenotype that occurred, and at what point in development it became apparent. PFAS mixtures significantly impacted growth parameters and exocrine pancreas length. The truncated pancreas phenotype was seen most often in the 16 μM PFHxS + 16 μM PFOS treatment group, so this concentration was used for subsequent experiments. Time lapse imaging (58 - 72 hpf, 80 - 96 hpf) and cellular proliferation assays (3 - 96 hpf) were used to ascertain the cause of the truncated phenotype as an issue of cellular migration or proliferation within the pancreas. Cell migration and proliferation were decreased in response to toxicant exposure. This study offers insights to how developmental exposures to toxicants may impact the pancreas.

DOI

https://doi.org/10.7275/30719483

First Advisor

Alicia Timme-Laragy

Second Advisor

Rolf Karlstrom

Third Advisor

Kimberly Tremblay

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