Experimental evidence of a limited impact of new-generation perfluoroalkyl substance C6O4 on differentiating human dopaminergic neurons from induced pluripotent stem cells

Autor: Andrea Di Nisio, Marta Trevisan, Stefano Dall’Acqua, Micaela Pannella, Claudia Pappalardo, Alberto Ferlin, Carlo Foresta, Luca De Toni
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Toxicology Reports, Vol 10, Iss , Pp 40-44 (2023)
Druh dokumentu: article
ISSN: 2214-7500
DOI: 10.1016/j.toxrep.2022.12.006
Popis: Perfluoroalkyl substances (PFASs) are persistent pollutants, raising concerns for human health. Legacy PFAS perfluoro-octanoic acid (PFOA) accumulate in brains of people at high environmental exposure, especially in areas enriched with dopaminergic neurons (DN). In vitro exposure to 10 ng/mL PFOA for 24 h was also associated with an altered molecular and functional phenotype of DN differentiated from human induced pluripotent stem cells (hiPSCs). Acetic acid, 2,2-difluoro-2-((2,2,4,5-tetrafluoro-5(trifluoromethoxy)− 1,3-dioxolan-4-yl)oxy)-ammonium salt (1:1), known as C6O4, is a new generation PFAS proposed to have a safer profile. Here we investigated the effect of C6O4 exposure on the molecular phenotype of hiPSC-derived DN. Cells were exposed to C6O4 for 24 h, at the concentration of 10 ng/mL, at neuronal commitment (DP1), neuronal precursor (DP2) and the mature dopaminergic (DP3) phases of differentiation. Liquid-chromatography/mass-spectrometry showed negligible cell accumulation of C6O4 at each differentiation stage and by staining with Merocyanine-540 we observed unaltered cell membrane fluidity. Immunofluorescence showed that the expression of tyrosine hydroxylase (TH) and βIII-Tubulin was unaffected by the exposure to C6O4 at each differentiation phase (respectively: DP1, p = 0.332; DP2, p = 0.623; DP3, p = 0.816, with respect to control unexposed conditions). Exposure to C6O4 is presumed to have minor effects on cell molecular/functional phenotype of developing human DN cells, requiring confirm on in vivo models.
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