Estrogen and Bisphenol A Affect Male Rat Enamel Formation and Promote Ameloblast Proliferation

Abstract

Bisphenol A (BPA) is a widespread endocrine disrupting chemical (EDC) strongly suspected to have adverse health effects. Numerous tissues and cells are affected by BPA, and we showed recently that BPA targets include ameloblasts and enamel. We therefore investigated the effects of BPA on ameloblasts and the possible involvement of the estrogen signaling pathway. Rats were exposed daily to low-dose BPA, and developed enamel hypomineralization similar to human molar incisor hypomineralization (MIH). BPA increased ameloblast proliferation in vivo and in vitro. The proliferation of the rat dental epithelial cell line HAT-7 was also increased by estrogen (E2). Ameloblasts express ERα but not ERβ both in vivo and in vitro. The ER antagonist ICI 182,780 was used to inactivate ERα and abolished the effects of E2 on cell proliferation and transcription, but only partially reduced the effects of BPA. In conclusion, we show, for the first time, that: 1) BPA has ER-dependent and ER-independent effects on ameloblast proliferation and gene transcription; 2) the estrogen signaling pathway is involved in tooth development and the enamel mineralization process; and 3) BPA impacts preferentially amelogenesis in male rats. These results are consistent with the steroid hormones having effect on ameloblasts, raising the issues of the hormonal influence on amelogenesis and possible differences in enamel quality between sexes.

Amelogenesis imperfecta in familial hypomagnesaemia and hypercalciuria with nephrocalcinosis caused byCLDN19gene mutations

“…The mandibles and kidneys (control tissue) were immediately sampled. The lower incisors were dissected out from the mandibles, and the enamel organ including ameloblasts and the adjoining epithelium were microdissected as previously described 33. Tissues were homogenised and total RNA was extracted using the TriReagent method (TriReagent, Euromedex, Strasbourg, France) as per the manufacturer's procedures.…”

Expression of Steroid Receptors in Ameloblasts during Amelogenesis in Rat Incisors

“…It may directly or indirectly modulate receptor activities, not only in maturation-stage ameloblasts, but also in pre-secretory and proliferating cells of the cervical loop. The ERα has already been shown to mediate, at least in part, the short-term mitogenic effects of BPA in pre-ameloblastic cells, but not genomic effects (Jedeon et al, 2014a). Similar non-genomic effects of BPA involving GPR30 activation has been shown in prostate cancer cells (Prins et al, 2014).…”

“…It also directly or indirectly interferes with the activity of the androgen receptor (AR), the progesterone receptor (PGR), the glucocorticoid receptor (GR), and the PPARγ (Acconcia et al, 2015; Rehan et al, 2015). The mechanism of action of BPA in dental cells is even less evident as its putative receptors are poorly defined in dental tissues, except for ERα (Jedeon et al, 2014a). …”

Chronic Exposure to Bisphenol A Exacerbates Dental Fluorosis in Growing Rats

“…(7) After verifying RNA integrity and quality, we analyzed the expression of enamel matrix genes by RT-qPCR ( Figure 2). The abundance of amelogenin (Amelx) mRNA was >250-fold higher and that of enamelin (Enam) was 1200-fold higher during the secretion (S) than the maturation (M) stage, confirming the accuracy of the dissection.…”