Bisphenol A induces otolith malformations during vertebrate embryogenesis

Abstract : BACKGROUND : 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. RESULTS: 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. CONCLUSIONS: 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.
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BMC Developmental Biology, BioMed Central, 2011, 11 (1), pp.4. 〈10.1186/1471-213X-11-4〉
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Yann Gibert, Sana Sassi-Messai, Jean-Baptiste Fini, Laure Bernard, Daniel Zalko, et al.. Bisphenol A induces otolith malformations during vertebrate embryogenesis. BMC Developmental Biology, BioMed Central, 2011, 11 (1), pp.4. 〈10.1186/1471-213X-11-4〉. 〈inserm-00622804〉



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