Effects of Low Dose Nonylphenol Exposure on the Proper Development of the Xenopus laevis Neural Crest

Abstract

Endocrine-disrupting compounds (EDCs) are ubiquitous substances found in many industrial solvents, pesticides, household cleaners, and plastics. These chemicals have been shown to have adverse morphological and neurological effects on organisms such as rats, fish, aquatic frogs, and the developing human embryo. The most commonly observed results of in vivo EDC exposure are deleterious effects on neural crest cell derivatives. In preliminary studies, Xenopus laevis embryos were exposed to concentrations of nonylphenol, a well-known EDC, ranging from 500nM to 1μM for periods of three days to two weeks. Distinct spinal cord and cranio-facial deformities as well as enlargements of the head and gut were the most consistently observed effects of these exposures and were seen most prevalently in the lowest concentration doses. Exposure experiments were repeated at lower 1nM, 5nM, and 10nM nonylphenol concentrations. The results of these exposures were similar to the higher dose experiments, yielding spinal cord malformations, cranio-facial deformities, and behavioral abnormalities. It was then hypothesized that these compounds were disrupting hormone-transcription pathways involved in neural crest cell differentiation and migration. Recent studies have shown that a member of the forkhead box gene family, FoxD3, is intimately involved in early neural crest cell migration and differentiation in Xenopus laevis. Western Blot analyses probing for the mis- expression of FoxD3 were performed on embryo lysate exposed to nonylphenol at the low dose concentrations for 72 hours. Results of these analyses supported FoxD3 down-regulation at the 5nM and 1nM treatments in four replicate blots.