The Mixture of Bisphenol-A and Its Substitutes Bisphenol-S and Bisphenol-F Exerts Obesogenic Activity on Human Adipose-Derived Stem Cells Reina Pérez, Iris Olivas Martínez, Alicia Mustieles Miralles, Vicente Salamanca Fernández, Elena Molina Molina, José Manuel Olea Serrano, Nicolás Fernández Cabrera, Mariana Fátima Mixtures Bisphenols Bisphenol A (BPA) Bisphenol S (BPS) Bisphenol F (BPF) Endocrine disruptors Dose addition Bisphenol A (BPA) and its substitutes, bisphenol F (BPF) and S (BPS), have previously shown in vitro obesogenic activity. This study was designed to investigate their combined effect on the adipogenic differentiation of human adipose-derived stem cells (hASCs). Cells were exposed for 14 days to an equimolar mixture of bisphenols (MIX) (range 10 nM-10 mu M). Oil Red staining was used to measure intracellular lipid accumulation, quantitative real-time polymerase chain reaction (qRT-PCR) to study gene expression of adipogenic markers (PPAR gamma, C/EBP alpha, LPL, and FABP4), and Western Blot to determine their corresponding proteins. The MIX promoted intracellular lipid accumulation in a dose-dependent manner with a maximal response at 10 mu M. Co-incubation with pure antiestrogen (ICI 182,780) inhibited lipid accumulation, suggesting that the effect was mediated by the estrogen receptor. The MIX also significantly altered the expression of PPAR gamma, C/EBP alpha, LPL, and FABP4 markers, observing a non-monotonic (U-shaped) dose-response, with maximal gene expression at 10 nM and 10 mu M and lesser expression at 1 mu M. This pattern was not observed when bisphenols were tested individually. Exposure to MIX (1-10 mu M) also increased all encoded proteins except for FABP4, which showed no changes. Evaluation of the combined effect of relevant chemical mixtures is needed rather than single chemical testing. 2022-07-14T10:54:39Z 2022-07-14T10:54:39Z 2022-05-27 info:eu-repo/semantics/article Reina-Pérez, I... [et al.]. The Mixture of Bisphenol-A and Its Substitutes Bisphenol-S and Bisphenol-F Exerts Obesogenic Activity on Human Adipose-Derived Stem Cells. Toxics 2022, 10, 287. [https://doi.org/10.3390/toxics10060287] http://hdl.handle.net/10481/76019 10.3390/toxics10060287 eng info:eu-repo/grantAgreement/EC/H2020/733032 http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Atribución 4.0 Internacional MDPI