Emerging contaminants and health: potential effects of endocrine disruptors on humans and the environment

Endocrine disruptors (EDs) constitute a critical global health challenge. Their ubiquitous environmental presence and ability to perturb intricate hormonal signaling are increasingly implicated in adverse neurological outcomes. This investigation examined the neurotoxic potential of six representative EDs -- pesticides (atrazine, cypermethrin, vinclozolin), industrial agents (diethyl phthalate, PFOS), and a pharmaceutical (17α-ethinyl estradiol) -- utilizing the SH-SY5Y human neuroblastoma cell line. Cellular viability, reactive oxygen species generation, and microRNA (miRNA) expression profiles were meticulously assessed. Exposure to pesticides elicited specific miRNA modulation (miR-200a-3p, miR-146b-5p, miR-29b-3p), targeting the pivotal PI3K/Akt/mTOR cell proliferation pathway. Molecular analysis revealed significant upregulation of key pro-proliferative markers (ADM12, Bcl-2, MMP2, CDK6, HDAC4, p-Akt/mTOR) alongside p53 downregulation. Conversely, diethyl phthalate, PFOS, and 17α-ethinyl estradiol induced a distinct miRNA downregulation (miR-18b-5p, miR-133b, miR-200a-3p, miR-653-5p), suggesting involvement of the Ras signaling cascade, with subsequent validation confirming modulation of pathway components (CDK6, SOS1, PTEN) and marked Ras pathway activation via Western Blot, particularly with 17α-ethinyl estradiol. The months spent at BioBasic Europe enabled a crucial step in bridging in vitro findings to human relevance. Specifically, prevalent ED sunscreen components, namely ethylhexyl salicylate and avobenzone, were identified in commercially available products and subsequently tested for their toxicity. Furthermore, nickel levels in these consumer products were also assessed to ascertain its presence. Collectively, these findings underscore the neurotoxic capacity of EDs through the dysregulation of gene expression and critical signaling pathways, warranting further mechanistic elucidation to inform effective preventative strategies against chronic environmental exposure. This research project was funded by the National Operational Programme Research and Innovation 2014-2020 (CCI 2014IT16M2OP005), ESF REACT-EU resources, Action IV.4 “Doctorates and research contracts on innovation topics” and Action IV.5 “Doctorates on Green topics".