Bisphenol A induces otolith malformations during vertebrate embryogenesis
1 Institut de Génomique Fonctionnelle de Lyon; Université de Lyon; Université Lyon 1; CNRS; INRA; Ecole Normale Supérieure de Lyon; 46 allée d'Italie, 69364 Lyon Cedex 07, France
2 CNRS UMR 7221, Département Régulations, Développement et Diversité Moléculaire, Muséum National d'Histoire Naturelle, 7 rue Cuvier, 75231 Paris Cedex 5, France
3 INSERM Equipe « Signalisation Hormonale, Environnement et Cancer ». Centre en recherche de cancérologie de Montpellier, Parc Euromédecine-CRLC Val d'Aurelle, F-34298 Montpellier Cedex 5, France
4 INRA, UMR 1089 Xénobiotiques, 180 chemin de Tournefeuille, BP 93173, F-31300 Toulouse, France
5 Karolinska Institutet, Department of Biosciences and Nutrition, Laboratory of Medical Nutrition, NOVUM KUS, SE-14186 Stockholm, Sweden
BMC Developmental Biology 2011, 11:4 doi:10.1186/1471-213X-11-4Published: 26 January 2011
The plastic monomer and plasticizer bisphenol A (BPA), used for manufacturing polycarbonate plastic and epoxy resins, is produced at over 2.5 million metric tons per year. Concerns have been raised that BPA acts as an endocrine disruptor on both developmental and reproductive processes and a large body of evidence suggests that BPA interferes with estrogen and thyroid hormone signaling. Here, we investigated BPA effects during embryonic development using the zebrafish and Xenopus models.
We report that BPA exposure leads to severe malformations of the otic vesicle. In zebrafish and in Xenopus embryos, exposure to BPA during the first developmental day resulted in dose-dependent defects in otolith formation. Defects included aggregation, multiplication and occasionally failure to form otoliths. As no effects on otolith development were seen with exposure to micromolar concentrations of thyroid hormone, 17-ß-estradiol or of the estrogen receptor antagonist ICI 182,780 we conclude that the effects of BPA are independent of estrogen receptors or thyroid-hormone receptors. Na+/K+ ATPases are crucial for otolith formation in zebrafish. Pharmacological inhibition of the major Na+/K+ ATPase with ouabain can rescue the BPA-induced otolith phenotype.
The data suggest that the spectrum of BPA action is wider than previously expected and argue for a systematic survey of the developmental effects of this endocrine disruptor.