Enamel defects resulting from environmental conditions and the way of life are public health concerns because of their high prevalence. As 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 of which are commonly encountered in human populations and used 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 of which the expression was affected by exposure to BPA or NaF. Among the most modulated, many are directly involved in amelogenesis (as Amelx, Enam, Klk4, Mmp12, Slc26a4 and Slc5a8), and can be regrouped as forming the “hypomineralization enamelome”. 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. This article is protected by copyright. All rights reserved.