Bisphenol A induces otolith malformations during vertebrate embryogenesis

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-？-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.Bisphenols represent a group of industrial chemicals, widely and abundantly used for the production of polycarbonate plastics and epoxy resins. The most common bisphenol, bisphenol A [2,2-bis(4-hydroxyphenyl)propane; BPA] is used in the manufacture of plastic wares, dental resins, food can lining and flame retardants. Total annual production of BPA in the world exceeds 2.5 million metric tons [1]. Bisphenols may be present in the environment as a result of direct release from manufacturing or processing facilities or release of unreacted monomers. According to the recent NTP report total environmental release of BPA in 2004 was 82 tons [2]. BPA is among the most frequent organic wastewater contaminants detected in ground water in the USA [3]. In the United States, the median reported BPA concentration in surface waters was 0.14 μg/L whereas in Europe, mean values of 0.0047 μg/L and 0.0052 μg/L were observed in Germany and Netherlands respectively [4-6]. However, BPA levels found in receiving waters near processing facilities can occasionally r