Endocrine-disrupting chemicals (EDCs), in particular plasticizers present in food wrapping materials, are very relevant to human health. Several studies have shown that EDCs may pose the greatest risk during prenatal and early postnatal development, especially when binding to members of the nuclear receptor (NR) superfamily. EDCs can mimic/suppress estrogen actions in the developing brain by binding to estrogen receptors (ERs), and also interfere with neural progenitors (NPs) homeostasis through activation of peroxisome proliferator-activated receptors (PPARs) and retinoid X receptors (RXRs). We used the ST14A immortalized neural progenitor cell line to simulate the effects of prenatal NPs exposure to EDCs. We found by RT-PCR that the following NRs were expressed: ERα, ERβ, PPARα, PPARβ, PPARγ, RXR. Plasticizers were chosen based on their computational affinity for these receptors. NPs were exposed for 24-48 hours to endogenous and synthetic estrogens (17-β-estradiol and ethinyl estradiol) and to the following plasticizers: Bisphenol A, Diisononyl phthalate, Diisodecyl phthalate, Diethileneglicol benzoate. Both estrogens were able to increase cell proliferation by about 30% at 24hrs. Bisphenol-A (10nM) had an estrogen-like behavior in enhancing cell number, but its action was still significant at 48hrs. At 200nM concentration, all plasticizers determined an early increase in proliferation, however only DiDP and DGB were able to sustain this positive modulation for 48hrs. Ongoing studies in our lab will determine the cellular pathways activated by these EDCs in NPs, in order to earn greater insight into how these molecules may influence and perturb the neurogenic process.
Endocrine disruptors and nuclear receptors in the control of neural progenitors proliferation
POMATTO, VALENTINA;COTTONE, Erika;BOVOLIN, Patrizia
2014-01-01
Abstract
Endocrine-disrupting chemicals (EDCs), in particular plasticizers present in food wrapping materials, are very relevant to human health. Several studies have shown that EDCs may pose the greatest risk during prenatal and early postnatal development, especially when binding to members of the nuclear receptor (NR) superfamily. EDCs can mimic/suppress estrogen actions in the developing brain by binding to estrogen receptors (ERs), and also interfere with neural progenitors (NPs) homeostasis through activation of peroxisome proliferator-activated receptors (PPARs) and retinoid X receptors (RXRs). We used the ST14A immortalized neural progenitor cell line to simulate the effects of prenatal NPs exposure to EDCs. We found by RT-PCR that the following NRs were expressed: ERα, ERβ, PPARα, PPARβ, PPARγ, RXR. Plasticizers were chosen based on their computational affinity for these receptors. NPs were exposed for 24-48 hours to endogenous and synthetic estrogens (17-β-estradiol and ethinyl estradiol) and to the following plasticizers: Bisphenol A, Diisononyl phthalate, Diisodecyl phthalate, Diethileneglicol benzoate. Both estrogens were able to increase cell proliferation by about 30% at 24hrs. Bisphenol-A (10nM) had an estrogen-like behavior in enhancing cell number, but its action was still significant at 48hrs. At 200nM concentration, all plasticizers determined an early increase in proliferation, however only DiDP and DGB were able to sustain this positive modulation for 48hrs. Ongoing studies in our lab will determine the cellular pathways activated by these EDCs in NPs, in order to earn greater insight into how these molecules may influence and perturb the neurogenic process.
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