Pure and Applied Chemistry

Abstract: Since the early 1990s, a substantial number of deformed frogs have been observed in North America, particularly in the upper Midwest and Canada. Attempts to understand the etiology of the deformed frog problem have met with limited success to date with nearly as many proposed explanations as research groups working on the problem. Models for the mechanism underlying the development of deformed frogs include parasite/predation, ultraviolet radiation, and chemical exposure. Each model has its strengths and weaknesses. Despite contentious debate among researchers, there is an overall consensus that the increasing prevalence of deformed frogs is the result of a water-borne contaminant that has recently appeared, or reached a critical concentration. Our detailed analysis of malformed frogs collected in Minnesota ponds and lakes suggested that limb patterning was being modified by the disruption of a retinoid-sensitive developmental signaling pathway. Accordingly, we focused in the identification and characterization of bioactive retinoids from lake water and showed that retinoid treatment of frog embryos at sensitive times of development could recapitulate the full spectrum of limb abnormalities observed in field specimens in the laboratory. These data have led to the conclusion that inappropriate modulation of retinoid signaling by environmental contaminants is the mechanism underlying the increased incidence of frog malformations.