AMHERST, Mass. - Some studies indicate that early life exposure to pollutants such as PCBs and phthalates can predispose people to disease. Now environmental scientist Alicia Timme-Laragy at the University of Massachusetts Amherst has received a five-year, $1.7 million grant from the National Institute of Environmental Health Sciences for a multi-level study of early life exposure to environmental contaminants and aberrant pancreas development, which may predispose one to diabetes.
Disease may result from environmental contaminant exposure in early life via oxidative stress, disrupted signaling pathways controlling embryo growth, or via subtle structural or functional changes to insulin-producing pancreatic beta cells, she notes. Results of this work will be relevant to public health officials concerned about such exposures as well as molecular biologists studying signaling pathways to gain a mechanistic understanding of disease processes very early in life.
The researchers will study toxic chemicals such as PCB 126, the non-stick coating perfluorooctanesulfonate (PFOS) and phthalates. Timme-Laragy says that "surprisingly little is known about how embryos respond to oxidative stress, or the impact of toxicant exposures on pancreas development." Her long-term goal is to understand how embryos respond to oxidative stress, and how toxic exposures contribute to diabetes during development.
"A lot of scientists are trying to understand these processes, but we will be doing something new by focusing at multiple levels on toxicant effects in pancreas development as a possible predisposition factor in diabetes," she says. "By looking at the genetics, the molecular biology and the biochemistry and links to health effects, we hope to find targets for prevention."
Because it is difficult to identify embryonic changes in mammalian models, the researchers at UMass Amherst's School of Public Health and Health Sciences including Timme-Laragy and Laura Vandenberg, with partners at Brigham Young and McMaster universities, will use zebrafish, a good model for human development. Embryonic zebrafish will be exposed to the toxic chemicals at different points during development to help the researchers identify possible sensitive windows of pancreas organ formation.
"Zebrafish embryos are transparent, so we can watch for changes fairly easily as they develop and the chemical exposure can be done without hurting the mother fish," she adds. She and colleagues believe theirs is one of the first studies to take a comprehensive look at toxicant effects on pancreas development and the role of oxidative stress as a mechanism for health effects.
The experiments will also include sequential exposures, a way to evaluate the effect of chemical mixtures on target outcomes, Timme-Laragy notes. She and colleagues will use a fluorescent redox biosensor, redox imaging and automated, time-lapse microscopy. It will also advance understanding of a poorly understood but critical fundamental biological process, that is the role of the redox environment in embryonic development, and identify specific targets for mitigation, the environmental toxicologist adds.
Many undergraduate, master of public health and doctoral students are expected to gain laboratory experience in zebrafish culture, identification of embryonic stages, screening for fluorescent markers, genotyping, DNA isolation, embryo imaging and recognition of microscopic malformations and abnormalities on this project.