Bisphenol A induces otolith malformations during vertebrate embryogenesis.
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.
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. vincent.laudet@ens-lyon.fr
Yann
Y
Gibert
Sana
S
Sassi-Messai
Jean-Baptiste
JB
Fini
Laure
L
Bernard
Daniel
D
Zalko
Jean-Pierre
JP
Cravedi
Patrick
P
Balaguer
Monika
M
Andersson-Lendahl
Barbara
B
Demeneix
Vincent
V
Laudet
D000818:Animals; D001559:Benzhydryl Compounds / Q000378:metabolism; D047108:Embryonic Development / Q000187:drug effects*; D052244:Endocrine Disruptors / Q000633:toxicity*; D004787:Environmental Pollution; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D017403:In Situ Hybridization; D010037:Otolithic Membrane / Q000002:abnormalities / Q000196:embryology* / Q000502:physiology; D010042:Ouabain / Q000494:pharmacology; D010636:Phenols / Q000378:metabolism / Q000633:toxicity*; D011960:Receptors, Estrogen / Q000378:metabolism; D011988:Receptors, Thyroid Hormone; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013963:Thyroid Hormones / Q000494:pharmacology; D014873:Water Pollutants; D014981:Xenopus; D015027:Zebrafish; D000098826:Bisphenol A Compounds; D000098833:Bisphenol F Compounds
D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D004958:Estradiol; D000077267:Fulvestrant; D010042:Ouabain; D010636:Phenols; D011960:Receptors, Estrogen; D011988:Receptors, Thyroid Hormone; D000254:Sodium-Potassium-Exchanging ATPase; D013963:Thyroid Hormones; D014873:Water Pollutants; C006780:bisphenol A; D000098826:Bisphenol A Compounds; C008745:4,4'-bisphenol F; D000098833:Bisphenol F Compounds
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