Liquid Crystal Monomers and Their Mixtures Alter Nuclear Receptor Signaling and Promote Adipogenesis In Vitro

Abstract Liquid crystal monomers (LCMs) are ubiquitous environmental contaminants released from electronic devices’ liquid crystal display (LCD) panels, which have led to the contamination of food, breast milk, and serum. As the toxicity of individual LCMs, not to mention their myriad mixtures, is currently very poorly characterized, there is a crucial need for investigations into the health hazards posed by exposure. In this study, 10 nonfluorinated (NF) and fluorinated (F) LCMs and 3 fluorination-based LCM mixtures were screened for metabolism and endocrine-disrupting potential in vitro at exposure-relevant concentrations using adipogenesis assays and luciferase reporter gene assays. Both NF-LCMs, F-LCMs, and their mixtures were found to alter the transcriptional activity of one or more nuclear receptors. Notably, 6 LCMs and all LCM mixtures were able to antagonize the progesterone receptor, with several displaying non-monotonic concentration-response curves. Multiple LCMs and their mixtures also increased triglyceride accumulation in murine preadipocytes and human mesenchymal stem cells in a concentration-dependent manner. The concentration addition principle underestimated the adipogenic potencies of LCM mixtures when compared with those derived from benchmark concentration analyses of empirical adipogenesis assay results, suggesting synergistic interactions. While no mechanistic pattern emerged between the bioactivities, results confirmed the metabolism and endocrine-disrupting potential of both NF-LCMs, F-LCMs, and their mixtures. This emphasizes the need to further investigate the metabolic and reproductive health impacts of LCM exposure in vivo, as well as the necessity of exploring alternative models to predict the toxicity of LCM mixtures.