Abstract
Bisphenol A (BPA) is one of the most widely used chemicals worldwide, e.g., as a component of plastic containers for food and water. It is considered to exert an estrogenic effect, by mimicking estradiol (E2) action. Because of this widespread presence, it has attracted the interest and concern of researchers and regulators. Despite the vast amount of related literature, the potential adverse effects of environmentally significant doses of BPA are still object of controversy, and the mechanisms by which it can perturb endocrine functions, and particularly the neuroendocrine axis, are not adequately understood. One of the ways by which endocrine disruptors (EDCs) can exert their effects is the perturbation of calcium signaling mechanisms. In this study, we addressed the issue of the impact of BPA on the neuroendocrine system with an in vitro approach, using a consolidated model of immortalized Gonadotropin-Releasing Hormone (GnRH) expressing neurons, the GT1–7 cell line, focusing on the calcium signals activated by the endocrine disruptor. The investigation was limited to biologically relevant doses (nM–µM range). We found that BPA induced moderate increases in intracellular calcium concentration, comparable with those induced by nanomolar doses of E2, without affecting cell survival and with only a minor effect on proliferation.
Highlights
Among the many chemical molecules present in the environment that can interact with the endocrine system and have been classified as endocrine disruptors, Bisphenol A (BPA) is one of the most widely used, e.g., as a component of plastic containers for food and water
One of the ways by which endocrine disruptors (EDCs) can exert their effects is the perturbation of calcium signaling mechanisms
We addressed the issue of the impact of BPA on the neuroendocrine system with an in vitro approach, using a consolidated model of immortalized Gonadotropin-Releasing Hormone (GnRH) expressing neurons, the GT1–7 cell line, focusing on the calcium signals activated by the endocrine disruptor
Summary
Among the many chemical molecules present in the environment that can interact with the endocrine system and have been classified as endocrine disruptors, Bisphenol A (BPA) is one of the most widely used, e.g., as a component of plastic containers for food and water. In vitro data referring to effects on neuronal models are even more scarce: a reduction in the differentiation of human stem cells into dopaminergic neurons has been reported [22]; and another study has reported effects on gene transcription in Gonadotropin-Releasing Hormone (GnRH) neurons and GT1–7 cells [23] In the latter experimental model, BPA has been shown to induce oxidative stress [24]. 4T).oTporporvoivdiedeinifnofromrmataitoinonoonntthhee cchannels involved in the generation of tthis iinnflfluuxx, wwee ppeerrffoorrmmeed tthhrreeee eexxppeerriimmeents ((nn == 140 cells; only cells that gave aarreessppoonnsseetotoKKCCl lwwereereanaanlaylzyezde)di)niwn hwichhic, hd,udriunrginagsuasstauisnteadinreedspreosnpsoentose5tμoM5 μBMPAB, 1P0A0, 1μ0M0 μNMiCNl2iCanl2da1n0dμ1M0 μnMifendifiepdinipei,nbel,obclkoecrkse,rrse,srpesepcteicvteivlye,lyo,foTf ‐Ta- nanddLL‐t-ytyppeeVVDDCCCCss,,wweerreeaaddddeedd to the medium This protocol has been shown to block most the calcium increase activated by chemical depolarization in tthheesse cceellllss [[4400]].
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