title: Chronic Exposure to Bisphenol A Exacerbates Dental Fluorosis in Growing Rats.
abstract: Enamel defects resulting from environmental conditions and way of life are public health concerns because of their high prevalence. Because their etiology is unclear, the aim of this study was to analyze the various forms of enamel hypomineralization, and to characterize the genes involved in this process to determine the mechanisms involved in disruptions of amelogenesis. We used bisphenol A (BPA) and fluoride as models; both are commonly encountered in human populations and utilized in dentistry. Wistar rats were chronically exposed to 5 μg/kg/day BPA from day 1 of gestation to day 65 after birth (P65) and 5 mM fluoride from P21 to P65. Resulting enamel defects were comparable to the human enamel pathologies molar incisor hypomineralization (MIH) and dental fluorosis (DF) respectively, and were more severe in rats exposed to both agents than to each agent alone. Large-scale transcriptomic analysis of dental epithelium showed a small group of genes the expression of which was affected by exposure to BPA or NaF. Among the most modulated, many are directly involved in amelogenesis (Amelx, Enam, Klk4, Mmp12, Slc26a4, and Slc5a8), and can be regrouped as forming the "hypomineralization enameloma." Each of these gene expression perturbations may contribute to enamel defects. Exposure to BPA weakens enamel, making it more prone to generate frequent mineralization defects MIH and DF. Our study identifies hypomineralization genes that may enable the use of dental enamel as an early marker of exposure to environmental toxicants because of its unique ability to retrospectively record ameloblast pathophysiology. © 2016 American Society for Bone and Mineral Research.
authors.affiliation: Cordeliers Research Centre Inserm UMRS 1138, Paris-Diderot University, Paris-Descartes University, Pierre & Marie Curie-Paris University, Laboratory of Molecular Oral Pathophysiology, Paris, France.|Paris-Diderot University, Faculty of Dentistry, Paris, France.|Centre de Référence des maladies rares de la face et de la cavité buccale MAFACE hôpital Rothschild, Paris, France.
authors.forename: Katia
authors.initials: K
authors.lastname: Jedeon
authors.affiliation: Cordeliers Research Centre Inserm UMRS 1138, Paris-Diderot University, Paris-Descartes University, Pierre & Marie Curie-Paris University, Laboratory of Molecular Oral Pathophysiology, Paris, France.|Paris-Diderot University, Faculty of Dentistry, Paris, France.|Groupe Hospitalier La Pitié Salpêtrière-Charles Foix, Paris, France.
authors.forename: Sophia
authors.initials: S
authors.lastname: Houari
authors.affiliation: Cordeliers Research Centre Inserm UMRS 1138, Paris-Diderot University, Paris-Descartes University, Pierre & Marie Curie-Paris University, Laboratory of Molecular Oral Pathophysiology, Paris, France.|Paris-Diderot University, Faculty of Dentistry, Paris, France.
authors.forename: Sophia
authors.initials: S
authors.lastname: Loiodice
authors.affiliation: Cordeliers Research Centre Inserm UMRS 1138, Paris-Diderot University, Paris-Descartes University, Pierre & Marie Curie-Paris University, Laboratory of Molecular Oral Pathophysiology, Paris, France.|Paris-Diderot University, Faculty of Dentistry, Paris, France.|Faculty of Odonto-Stomatology, Ho Chi Minh University of Medicine and Pharmacology, Ho Chi Minh-Ville, Vietnam.
authors.forename: Tran Thu
authors.initials: TT
authors.lastname: Thuy
authors.affiliation: Cordeliers Research Centre Inserm UMRS 1138, Paris-Diderot University, Paris-Descartes University, Pierre & Marie Curie-Paris University, Laboratory of Molecular Oral Pathophysiology, Paris, France.
authors.forename: Manon
authors.initials: M
authors.lastname: Le Normand
authors.affiliation: Cordeliers Research Centre Inserm UMRS 1138, Paris-Diderot University, Paris-Descartes University, Pierre & Marie Curie-Paris University, Laboratory of Molecular Oral Pathophysiology, Paris, France.|Paris-Diderot University, Faculty of Dentistry, Paris, France.|Centre de Référence des maladies rares de la face et de la cavité buccale MAFACE hôpital Rothschild, Paris, France.
authors.forename: Ariane
authors.initials: A
authors.lastname: Berdal
authors.affiliation: Cordeliers Research Centre Inserm UMRS 1138, Paris-Diderot University, Paris-Descartes University, Pierre & Marie Curie-Paris University, Laboratory of Molecular Oral Pathophysiology, Paris, France.|Paris-Diderot University, Faculty of Dentistry, Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Babajko
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000009:adverse effects*; D002648:Child; D003743:Dental Enamel / Q000378:metabolism; D018450:Disease Progression; D004848:Epithelium / Q000187:drug effects; D005260:Female; D009050:Fluorosis, Dental / Q000235:genetics / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010447:Peptide Hydrolases / Q000378:metabolism; D010636:Phenols / Q000009:adverse effects*; D017208:Rats, Wistar; D012969:Sodium Fluoride / Q000494:pharmacology; D055815:Young Adult; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D010447:Peptide Hydrolases; D010636:Phenols; D012969:Sodium Fluoride; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: ANIMAL MODELS; DENTAL BIOLOGY; ENAMEL; FLUOROSIS; MINERALIZATION