Silent killers in your everyday products: Unveiling the neurotoxic effects of endocrine disrupting molecules

Endocrine disruptors (EDs) are ubiquitous compounds with the ability to interfere with endogenous hormones. Molecules identified as EDs are highly heterogeneous, but most of them are man-made chemicals, such as ethinyl estradiol (EE), medication, perfluorooctanesulfonic-acid (PFOS), surfactant, and diethyl-phthalate (DP), plasticizer. The constant exposure of the global population to these molecules can lead to an induction of toxic effects, especially on the central nervous system. Among the different mechanisms by which EDs could influence human health, of interest is the modulation of microRNA (miRNA). The aim of the present project was to study the impact of exposure to subtoxic concentrations of EE, PFOS and DP in the mechanisms of neurotoxicity, focusing on the modulation of miRNAs implicated in neuronal functions. The human neuroblastoma cell line SH-SY5Y was exposed to the molecules in study. Afterwards, a profiling unveiled a modulation in the expression of some miRNAs implicated in neurotoxicity. Computational analysis to determine the target genes revealed that most of them were involved in RAS pathway, which regulates cell proliferation, survival and differentiation. RT-PCR to validate the pathway showed an up regulation of the genes EGFR, IGF1R, AREG, EZH2 and SOX30, while Western Blotting identified an upregulation in the phosphorylation of Akt and mTOR, while p53 underwent downregulation. These preliminary analyses allow to investigate the role of EE, PFOS and DP as EDs able to induce modulation in pathways involved in neurodegeneration and development of cancer. Funded by Project PON. Thanks to Fondazione del Monte di Bologna e Ravenna (Prot. 1355bis/2021).