Endocrine Abstracts

Bisphenol A (BPA) is an environmental estrogen that is globally used in the production of plastics. Studies on BPA as an endocrine disruptor have focused on its estrogenic activity in vitro and in adult animal models. Recently, the National Toxicology Program at the US National Institutes of Health raised concerns for the neural and behavioral effects of BPA in fetuses, infants, and children at the currently allowed human exposures. However, the difficulty in studying uterus-enclosed mammalian embryos has hampered the analysis of the effects of BPA on vertebrate development. In vitro studies have suggested that BPA can bind to and antagonize thyroid hormone (T3) activation of T3 receptor (TR). Because small perturbations in T3 homeostasis can severely and adversely affect human health and development, we propose the use of Xenopus laevis metamorphosis as a model to study the effect of BPA on T3-dependent vertebrate development. Amphibian metamorphosis requires T3 and encompasses the postembryonic period in mammals (a few months before and several months after birth in human) when T3 action is most critical. We show here that BPA inhibits T3-induced metamorphosis of Xenopus laevis by blocking T3-dependent gene regulation pathway. Importantly, microarray analysis also indicates that most of the genes affected by BPA are T3-response genes, suggesting that BPA mainly affects T3- but not the estrogen-signaling pathways during metamorphosis. Our finding that this endocrine disruptor well known for its estrogen-like activity in vitro functions to inhibit T3-pathway to affect vertebrate development in vivo thus not only implicates potential deleterious effects of BPA on human embryonic development but also demonstrates the importance of studying endocrine-disruption in a developmental context in vivo.