Investigating the Mechanisms Driving Stunted Pancreata in PFOS-Exposed Larval Zebrafish (Danio rerio)
Presenter: Autumn E. Whelan
Faculty Sponsor: Alicia Timme-Laragy
School: UMass Amherst
Research Area: Public Health and Epidemiology
Session: Poster Session 5, 3:15 PM - 4:00 PM, Auditorium, A25
ABSTRACT
Perfluorooctane sulfonic acid, or PFOS, is a “forever chemical” characterized by a long half life in humans and prolonged persistence in the environment. Human exposure through contaminated drinking water has led to detectable levels in 98% of the entire U.S. population, and its presence in the umbilical cord suggests it can be transferred from mother to fetus. Previous work in the Timme-Laragy lab using zebrafish as a model organism found that embryonic exposures to PFOS are associated with the presence of markers linked to metabolic syndrome and diabetes, including decreased islet size and pancreas length, elevated insulin and cholesterol, insulin resistance, and altered beta cell function. However, the underlying mechanisms of PFOS-induced metabolic dysfunction are multimodal and not fully understood. Because silencing of Notch signaling is required for pancreatic acinar cell differentiation, we hypothesize that developmental PFOS exposure disrupts the exocrine pancreas through inappropriate prolonged Notch activation, stunting pancreatic elongation. To test this hypothesis, transgenic zebrafish Tg(TP1:GFP;ins:mCherry) embryos are used to observe expression of the Notch reporter in the pancreatic bud following PFOS exposure in comparison to a Notch pathway inhibitor. Initial experiments display prolonged Notch activity in the pancreatic bud at 32 hours post fertilization, supporting the hypothesis. This work will provide insight into the developmental signaling pathways perturbed by PFOS to impact pancreas development.