title: Enamel defects reflect perinatal exposure to bisphenol A.
abstract: Endocrine-disrupting chemicals (EDCs), including bisphenol A (BPA), are environmental ubiquitous pollutants and associated with a growing health concern. Anecdotally, molar incisor hypomineralization (MIH) is increasing concurrently with EDC-related conditions, which has led us to investigate the effect of BPA on amelogenesis. Rats were exposed daily to BPA from conception until day 30 or 100. At day 30, BPA-affected enamel exhibited hypomineralization similar to human MIH. Scanning electron microscopy and elemental analysis revealed an abnormal accumulation of organic material in erupted enamel. BPA-affected enamel had an abnormal accumulation of exogenous albumin in the maturation stage. Quantitative real-time PCR, Western blotting, and luciferase reporter assays revealed increased expression of enamelin but decreased expression of kallikrein 4 (protease essential for removing enamel proteins) via transcriptional regulation. Data suggest that BPA exerts its effects on amelogenesis by disrupting normal protein removal from the enamel matrix. Interestingly, in 100-day-old rats, erupting incisor enamel was normal, suggesting amelogenesis is only sensitive to MIH-causing agents during a specific time window during development (as reported for human MIH). The present work documents the first experimental model that replicates MIH and presents BPA as a potential causative agent of MIH. Because human enamel defects are irreversible, MIH may provide an easily accessible marker for reporting early EDC exposure in humans.
authors.affiliation: Laboratory of Molecular Oral Pathophysiology, INSERM UMRS 872, Cordeliers Research Center, Paris, France.
authors.forename: Katia
authors.initials: K
authors.lastname: Jedeon
authors.forename: Muriel
authors.initials: M
authors.lastname: De la Dure-Molla
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Brookes
authors.forename: Sophia
authors.initials: S
authors.lastname: Loiodice
authors.forename: Clémence
authors.initials: C
authors.lastname: Marciano
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kirkham
authors.forename: Marie-Chantal
authors.initials: MC
authors.lastname: Canivenc-Lavier
authors.forename: Sofiane
authors.initials: S
authors.lastname: Boudalia
authors.forename: Raymond
authors.initials: R
authors.lastname: Bergès
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Harada
authors.forename: Ariane
authors.initials: A
authors.lastname: Berdal
authors.forename: Sylvie
authors.initials: S
authors.lastname: Babajko
mesh_terms: D000566:Amelogenesis / Q000187:drug effects; D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D003744:Dental Enamel Hypoplasia / Q000139:chemically induced* / Q000378:metabolism; D003746:Dental Enamel Proteins / Q000378:metabolism; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D006801:Humans; D007610:Kallikreins / Q000378:metabolism; D008297:Male; D008855:Microscopy, Electron, Scanning; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D015415:Biomarkers; D003746:Dental Enamel Proteins; D052244:Endocrine Disruptors; D007610:Kallikreins; D010636:Phenols; C038456:tuftelin; C120801:kallikrein 4; C006780:bisphenol A; D000098826:Bisphenol A Compounds