Abstract
BackgroundThe 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.ResultsWe 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.ConclusionsThe 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.
Highlights
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
BPA exposure during early embryogenesis induces abnormalities of the otoliths Zebrafish embryos were treated from 5 hours post-fertilization onwards with concentrations of BPA ranging from 0.01 μM to 100 μM
While exposure to BPA
Summary
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. 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
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