Suppression of amphibian metamorphosis by bisphenol A and related chemical substances

This investigation attempts to clarify the effects of the plastic monomer bisphenol A (BPA) and related chemicals on 3,3',5-triiodothyronine (T-3)-induced and spontaneous anuran tadpole tail regression. T-3-induced tail regression was found to be suppressed by BPA and tetrabromobisphenol A (TBBPA), tetrachlorobisphenol A (TCBPA), and tetramethylbisphenol A (TMBPA). T-3-treated Rana rugosa tadpole tails displayed marked apoptotic features, including DNA fragmentation and ladder-like profiles, as opposed to essentially little or no fragmentation and ladder formation for BPA, TBBPA, TCBPA and TMBPA-treated tails. BPA and related compounds also inhibited Silurana tropicalis spontaneous metamorphosis controlled by endogenous circulating thyroid hormone (TH). These results indicate that BPA and related compounds are TH antagonists. In transgenic Xenopus laevis tadpoles carrying plasmid DNA containing TH response element (TRE) and 5'-upstream promoter region of the TH receptor (TR) beta AI gene linked to a green fluorescent protein (EGFP) gene, T-3 induced a strong EGFP expression in the hind limbs, while T-3 plus BPA, TBBPA, TCBPA or TMBPA Suppressed the expression, suggesting BPA and related chemicals all act in preventing the binding of T-3 to TR, resulting in inhibition of TR-mediated gene expression.