Bisphenol A induces otolith malformations during vertebrate embryogenesis

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.

Analysis and occurrence of endocrine-disrupting compounds and estrogenic activity in the surface waters of Central Spain

“…Nevertheless, the European Commission periodically re-evaluates information the available and makes the proposed listing where appropriate. The ecotoxicological effects of BPA include reduced fertility and sperm quality, inhibition of ovulation in several species of fishes, alteration of the development of tadpoles' tails in frog species and anomalies in the development of zebrafish otoliths during early embryogenesis (Gibert et al, 2011). In addition, several recent studies Teng et al, 2013) have analyzed the possible estrogenic activity of BPA (e.g.…”

Bisphenol A Exposure During Early Development Induces Sex-Specific Changes in Adult Zebrafish Social Interactions

“…Because it is considered by many as a xenoestrogen, BPA has been associated with a range of molecular and physiological processes that may affect social behaviors, especially those linked to sex-specific activity patterns, e.g., alterations in gene expression (fish: Hatef et al 2012; Ribeiro et al 2012; rats: Li et al 2014), organ development (general vertebrates: Gibert et al 2011; Masuo and Ishido 2011; fish: Molina et al 2013; Huang et al 2012; Mihaich et al 2012; Cao et al 2010), and the hypothalamic-pituitary-gonadal axis activity (rats: Li et al 2014). While it was shown to bind to a range of hormone receptors (human: Prasanth et al 2010; fish: Jiao and Cheng 2010), there has been particular interest in BPA binding to estrogen receptors (ER), e.g., ERα, ERβ, and estrogen-related receptor gamma, ERRγ (general vertebrate: Ben-Jonathan and Steinmetz 1998; human: Takayanagi et al 2006; fish: Saili et al 2012; mice: Kundakovic et al 2013; rat: Cao et al 2013;).…”

Nuclear receptor research in zebrafish

“…Using receptor antagonists, the behavioral effects of flavonoids were demonstrated to be independent of ER activity (Bugel et al 2016). Finally, BPA has been shown to induce otolith malformations during development (Gibert et al 2011). Although it is commonly suggested that ER is the receptor mediating this effect, it was shown that these malformations are ERRγ dependent using morpholino knockdown and overexpression by mRNA injection (Tohme et al 2014).…”