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.

On the Variable Clinical Presentation of Molar-Incisor Hypomineralization

“…Amelogenins were thought to inhibit growth of crystallites until completely removed, but evidence from Klk4 ablated mice, in which amelogenins are not completely removed, show crystallites can grow despite the presence of remaining amelogenin [Simmer et al, 2009]. Indeed, we do not see much remnant of amelogenin in MIH lesions, mostly albumin and some α-fetoprotein [Jedeon et al, 2013]. These suggest that the main differences in clinical presentation of MIH may be primarily defined by variations that are in turn dependent on gene regulation.…”

“…In fact, disruptions of the connective tissues close to the epithelial papillary layer due to overexpression of Mmp20 in mice disrupt normal ameloblast migration [Shin et al, 2016]. In the case of MIH, diffusion of blood proteins occurs, from blood vessels in the connective tissues surrounding the papillary layer, into the enamel matrix during the maturation stage [Jedeon et al, 2013]. Disruptions of the system therefore relate to fluid movement from the outside towards the enamel organ, and it is likely that such disruptions are related to genetic variation.…”

Chronic Exposure to Bisphenol A Exacerbates Dental Fluorosis in Growing Rats

“…The number of animals necessary to get significant data was previously determined. (6,7) Four rats from each group were randomly selected for histological analysis, anesthetized by isofurane inhalation and perfused with 4% paraformaldehyde (PFA) (Sigma-Aldrich, St. Louis, MO) in phosphate-buffered saline (PBS; pH 7.4). Four other rats from each group were also randomly selected for micro computed tomography (µCT) and scanning electron microscopy (SEM) analysis.…”

L’émail

“…Des travaux expérimentaux ont montré des liens entre le MIH et l'exposition à différents agents environnementaux pendant la période périnatale. Cette anomalie relativement fréquente est associée au problème émergeant des perturbateurs endocriniens (notamment le bisphénol A) [28,29], omniprésents et dont la fenêtre de sensibilité maximale s'étend de la vie foetale à la petite enfance [30]. Ces polluants environnementaux peuvent interagir avec certains récepteurs hormonaux et altérer ainsi la quantité de peptides matriciels sécrétés en modulant leur niveau d'expression.…”