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.

Expression of Steroid Receptors in Ameloblasts during Amelogenesis in Rat Incisors

“…The anatomically distinguishable cervical loop was dissected from the apical end of the incisor. Microdissection quality was validated by RT-PCR using Enamelin primers for the secretion stage, and KLK4 or SLC26A4 for the maturation stage; Jedeon et al, 2016a). The absence of contamination by the mesenchyme and bone was verified using osteocalcin primers.…”

“…The proteases degrade the enamel matrix allowing subsequent mineral crystal growth under the correct pH and ionic conditions [aided by several solute carriers (SLCs) and ion-handling proteins]. BPA modulates the expression of at least one enamel key gene at each stage of amelogenesis, including enamelin, KLK4, and SLC26A4 (Jedeon et al, 2013, 2016a). The resulting rat enamel defects may be scored as those observed in human Molar Incisor Hypomineralization (MIH; Jedeon et al, 2013), a recently described enamel pathology (Weerheijm et al, 2001; Weerheijm and Merjare, 2003).…”

La sphère orale, cible et marqueur de l’exposition environnementale

“…L'implication des récepteurs des hormones stéroïdiennes (progestérone et androgènes) dans les mécanismes d'action du fluor sur les améloblastes [37] laisse ainsi suspecter de fortes interactions entre fluor et PE. D'ailleurs, le fluor et le BPA peuvent avoir des effets complémentaires et additionnels comme perturbateurs de l'amélogénèse [38]. Ceci pourrait expliquer l'accroissement de la sensibilité au fluor et une augmentation des fluoroses dans la population [39].…”

Disruption of Steroid Axis, a New Paradigm for Molar Incisor Hypomineralization (MIH)

“…Consequently, the effects of EDCs combinations are unpredictable. For example, combination of low doses of BPA with low doses of genistein and vinclozolin, two other EDCs, didn't lead to a greater phenotype (Jedeon et al, 2014a) whereas combination of BPA with fluoride increased enamel hypomineralization (Jedeon et al, 2016a). Enamel defects have also been associated to exposure to dioxin (Alaluusua et al, 2004) and PCBs (Jan et al, 2007), two groups of pollutants presenting EDC activity.…”

“…It is noteworthy that both factors increase enamel hypomineralization in the presence of fluoride (Salmela et al, 2011; Sahlberg et al, 2013) and the importance of the perinatal exposure to these agents has been underlined (Alaluusua et al, 2002). Even if fluoride is probably not a causal factor of MIH, experimental fluoride in combination with EDCs was shown to increase enamel hypomineralization (Salmela et al, 2011; Sahlberg et al, 2013; Jedeon et al, 2016a). …”