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Transcriptomics and relative potency assessments using Bench Mark Dose of Bisphenol A, Bisphenol S, Bisphenol F, and 3,3',5,5'-Tetrabromobisphenol A in H9 human embryonic stem cells

ABSTRACT: In this study we used RNA-seq to characterize the dose-response for global transcriptomic alterations induced by BPA, BPF, BPS and TBBA in H9 (WA09) human embryonic stem (hES) cells. To assess the relative biological activity and potency of BPA and structural analogs BPS, BPF and TBBP, we examined the stem cell transcriptome in H9 hES cells following exposure to these chemicals at concentrations that covered greater than three orders of magnitude (1 microM to >100 microM). These exposure levels are considered to be near human relevant and range from noncytotoxic to overtly toxic. Overall, this study provides basic mechanistic information about the effects of BPA and structural analogs BPS, BPF and TBBP on the transcriptome of hES cells and demonstrates how these data can be applied to derive benchmark dose modeling (BMD) information useful for comparing relative potencies of these structurally related chemicals.

ORGANISM(S): Homo sapiens

PROVIDER: GSE153320 | GEO | 2021/07/19

REPOSITORIES: GEO

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Project description:Bisphenols are used in the process of polymerization of polycarbonate plastics and epoxy resins, which have numerous applications in a variety of consumer products. Due to their hydrophobic properties, bisphenols can easily migrate out of plastic products especially into fatty foods. They have been found in brain, liver, adipose tissue and body fluids, illustrating their environmental prevalence. By increasing colonic inflammation in mice, disrupting the intestinal bacterial community structure and altering the microbial membrane transport system in zebrafish, bisphenols seem to interfere with the gut microbiome. The highly abundant human commensal bacterium Bacteroides thetaiotaomicron was exposed to bisphenols (Bisphenol A (BPA), Bisphenol F (BPF), Bisphenol S (BPS)), to examine the mode of action, in particular of BPF. All chemicals caused a concentration-dependent growth inhibition and the half-maximal effective concentration (EC50) corresponded to their individual logP values, a measure of their hydrophobicity. B. thetaiotaomicron exposed to BPF decreased membrane fluidity with increasing BPF concentrations. Physiological changes including an increase of acetate concentration were observed in cells treated with 0.57 mM BPF. On the proteome level, a higher abundance of several ATP synthase subunits and multidrug efflux pumps suggested an increased energy demand for adaptive mechanisms after BPF exposure. Defence mechanisms were also implicated by a pathway analysis, that identified a higher abundance of members of resistance pathways/strategies to cope with xenobiotics (i.e. antibiotics). Here, we present further insights into the mode of action of bisphenols in a human commensal gut bacterium regarding growth inhibition, and the physiological and functional state of the cell. These results, combined with microbiota-directed effects, could lead to a better understanding of host health disturbances and disease development based on xenobiotic uptake.

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Transcriptomics and relative potency assessments using Bench Mark Dose of Bisphenol A, Bisphenol S, Bisphenol F, and 3,3',5,5'-Tetrabromobisphenol A in H9 human embryonic stem cells

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