CRU webinar: The wrong place at the wrong time: Redox stress and toxicants in the zebrafish embryo

Abstract

Glutathione (GSH) is the most abundant endogenous cellular redox buffer, and plays key roles in vertebrate embryonic development and organogenesis. The GSH system in the embryo changes in both quantity and redox potential at different stages of development in specific and dynamic ways that can define critical windows of susceptibility to chemical-induced redox stress. Further, the ability of the GSH system to respond and recover from redox stress changes throughout development. Investigating changes in GSH during this vulnerable period of life has been challenging, as it has been difficult to obtain organ-specific data.

The zebrafish embryo is transparent, develops externally to the mother, and is highly permeable to dyes and other small molecules. By applying the GSH dye monochlorobimane (MCB) to the zebrafish at different stages of development, we have demonstrated that this presents an unbiased tool with which to examine organ-specific changes to GSH utilization in vivo. The brain and heart demonstrated the largest endogenous changes in MCB staining over four days of development, as well as dynamic responses to GSH modulation. The GI tract showed changes with redox-active toxicants perfluorooctanesulfonic acid (PFOS) and mono-(2-ethyl-hexyl)phthalate (MEHP) in a dose and age-dependent manner that correlate with structural changes to the pancreas within that region; endocrine pancreas morphology is most sensitive to redox-chemical induced changes at 48 hours post fertilization.

Using BioGEE, we further showed differential glutathionylation in the endocrine vs. exocrine pancreas. As numerous toxicants affect the glutathione system, understanding where and when this occurs in the embryo can help identify sensitive target tissues of redox-active toxicants.

Biography

Dr. Alicia Timme-Laragy is an Associate Professor of Environmental Health Sciences in the School of Public Health and Health Sciences at the University of Massachusetts Amherst (UMASS). She also holds faculty positions in the Models to Medicine program in the Institute for Applied Life Sciences, the Molecular Cell Biology graduate program, and is an adjunct faculty member in the Biology Department at UMASS. She is also a Guest Investigator at the Woods Hole Oceanographic Institution. She received her Ph.D. in 2007 from Duke University’s Nicholas School of the Environment through the Integrated Toxicology and Environmental Health Program. Her postdoctoral work was conducted in the Biology Department at the Woods Hole Oceanographic Institution. Her NIH-NIEHS-funded laboratory at UMASS (established in 2013) uses the zebrafish and cell culture models to study mechanisms of oxidative stress and antioxidant defenses during embryonic development, with a focus on the pancreas and environmental toxicants including PFAS.

Dr. Timme-Laragy is also active in public engagement, providing education on PFAS toxicity to affected communities and elected officials in Massachusetts. She is a member of the Society of Toxicology, the Society of Environmental Toxicology and Chemistry (SETAC), and the Society of Redox Biology and Medicine. She serves on the Scientific Program Committee of the Society of Toxicology, and the Scientific Advisory Board for the EPA National Estuary Program at Narragansett Bay.