Superfund Research Program
Altering the Balance of Adipogenic and Osteogenic Regulatory Pathways from Early Life Exposure to HPCs and AOPEs
Within this project, the team is investigating how specific hazardous contaminants affect the developing organism, and specifically, how they affect the development of bone and fat cells. Some of these contaminants have a chemical structure that is similar to hormones in the human body, and they have the potential to bind and activate specific pathways in a way that can perturb development. The team has demonstrated that early life exposures to select flame retardants result in adverse effects on both bone and fat development. In fish models, the team establishes that flame retardants profoundly alter the course of skeletal development resulting in osteogenic effects that mimic improper spinal growth and development. In a human stem cell model, the team shows that select flame retardants promote formation of fat depots which may be associated with enhanced accumulation of adipose (fat). The team also evaluated effects of environmentally relevant exposures in a biological assay that investigates the ability of chemicals to inhibit thyroid hormone regulation within the cell. Using silicone wristbands worn by research participants, the team extracted the chemicals from the wristbands and tested the mixture in a thyroid assay for activity. The team found that a majority of the wristband extracts inhibited thyroid receptor activity, and this activity was significantly correlated to the concentrations of some flame retardants measured on the wristbands (Kassotis 2020). These results suggest that environmentally relevant mixtures that humans are commonly exposed to have the capacity to influence hormone regulation in the body.