Rebecca C. Fry, Ph.D.
University of North Carolina, Chapel Hill
NIEHS Grants T32ES007018, P42ES005948, R01ES019315, P30ES010126
NIEHS grantees used computational analysis followed by laboratory testing to identify the glucocorticoid receptor pathway as a key mediator in metal-induced birth defects. This systems biology approach could be useful for predicting other biological pathways involved in environmentally induced birth defects.
The researchers selected arsenic, cadmium, chromium, lead, mercury, nickel, and selenium for a computational analysis that predicted genes and pathways associated with both metal exposure and developmental defects. This analysis predicted the glucocorticoid receptor pathway as a key mediator of multiple metal-induced birth defects. The researchers then evaluated this pathway with a whole chick embryo culture assay and an in vitro assay. In the chick embryo model, inhibiting the signaling of the glucocorticoid receptor pathway prevented structural malformations induced by inorganic arsenic. For the in vitro assay, the researchers observed partial to complete toxicity protection from inorganic arsenic and cadmium, when the glucocorticoid receptor was inhibited.
Citation: Ahir BK, Sanders AP, Rager JE, Fry RC. 2013. Systems biology and birth defects prevention: blockade of the glucocorticoid receptor prevents arsenic-induced birth defects. Environ Health Perspect 121:332-338.