Bisphenol A alternatives can effectively substitute for estradiol in promoting cell growth through estrogen receptor alpha in human breast cancer cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE85350 | GEO | 2017/03/03
SECONDARY ACCESSION(S): PRJNA338240
REPOSITORIES: GEO
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Project description:Bisphenol A (BPA) analogs, bisphenol B (BPB) and bisphenol AF (BPAF) have been widely detected in the environment and human products with increasing frequency. However, uterine health risks caused by BPBBisphenol A (BPA) analogs, bisphenol B (BPB) and bisphenol AF (BPAF) have been widely detected in the environment and human products with increasing frequency. However, uterine health risks caused by BPB and BPAF exposure need to be further elucidated. The study aimed to explore whether BPB or BPAF exposure will induce adverse outcomes in uterus. We then performed gene expression profiling using data obtained from mouse uterus exposed to BPB and BPAF at 28 days.
2023-05-12 | GSE223464 | GEO
Project description:Bisphenol A (BPA), which is used in a variety of consumer-related plastic products, was reported to cause metabolic disruption. Substitute compounds are increasingly emerging, but are not sufficiently investigated. In this study, we aimed to investigate the mode of action of BPA and four of its substitutes during the differentiation of human preadipocytes. Human preadipocytes were exposed to BPA, BPS, BPB, BPF, and BPAF, as well as the PPARγ-antagonist GW9662. After 12 days of differentiation, global protein profiles were assessed using LC-MS/MS-based proteomics.
2021-08-05 | PXD023227 | Pride
Project description:The widely used chemical bisphenol A (BPA) has been associated with several health effects. In recent years, many derivatives were developed to replace BPA without thorough toxicological evaluation. Here, we employed a human embryoid body (EB)-based in vitro global differentiation and hepatic specification models, followed by RNA-seq analyses, to comprehensively study the potential developmental toxicity of six BPA replacements (BPS, BPF, BPZ, BPB, BPE, and BPAF), as compared to BPA. We found that bisphenols may disrupt lineage commitment and lipid metabolism during early embryonic development. These effects mostly manifested via the dysregulation of HOX and APO family genes. Moreover, among the seven bisphenols analyzed, BPE, due to lower potential developmental toxicity, stood out as a relatively safe substitute of BPA in many applications, especially for infant/baby products.
2020-10-27 | GSE149753 | GEO
Project description:Bisphenol compounds (BPs) have various industrial uses and can enter the environment through various sources. To evaluate the ecotoxicity of BPs and identify potential gene candidates involved in the plant toxicity, Arabidopsis thaliana was exposed to bisphenol A (BPA), BPB, BPE, BPF, and BPS at a concentration of 1, 3, 10 mg/L for a duration of 14 days, and their growth status were monitored. At day 14, roots and leaves samples were collected for internal BPs exposure concentration detection, RNA-seq, and morphological observations. As shown in the results, exposure to BPs significantly disturbed root elongation, exhibiting a trend of stimulation at low concentration and inhibition at high concentration. Additionally, BPs exhibited pronounced generation of ROS, while none of the pollutants caused significant changes in root morphology. Internal exposure concentration analysis indicate that BPs tend to accumulate in the roots, with BPS exhibiting the highest level of accumulation. The results of RNA-seq indicate that shared 211 differently expressed genes (DEGs) of these 5 exposure groups are enriched in defense response, generation of precursor metabolites, response to organic substance, response to oxygen-containing, response to hormone, oxidation-reduction process and so on. Regarding unique DEGs in each group, BPS was mainly associated with the redox pathway, BPB primarily influenced seed germination, and in BPA, BPE and BPF were primarily involved in metabolic signaling pathways. Our results provide new insights for BPs induced adverse effects on Arabidopsis thaliana and suggest that the ecological risks associated with BPA alternatives cannot be ignored. At 14 d, roots in 3 mg/kg BPA, BPB, BPE, BPF and BPS exposure groups and the control were collected for RNA-seq analysis.
2023-12-19 | GSE250123 | GEO
Project description:Bisphenol A (BPA), widely used in plastics and resins, raised health concerns for its endocrine-disrupting effects. BPA analogues like bisphenol S (BPS) and bisphenol F (BPF) emerged as alternatives but were found to exhibit similar risks. Despite many countries have implemented BPA regulations, alternatives remain insufficiently regulated Although the safety of BPS and BPF has not been sufficiently verified, they have already been detected in various surrounding environments and human urine, raising serious concerns Bisphenols are expected to have various adverse effects, but research on this is lacking. This study explores the adverse effects of bisphenol mixtures on rats from fetus to young adulthood, analyzing transcriptomes by tissue and gender to identify key genes impacted by bisphenol exposure. Dams were orally administered test substances from gestational day 6 to lactation day 6. F1 pups received the same substances at half the concentration from postnatal day 7 to day 63. The tissues collected from the pups were subjected to transcriptome analysis, and core genes were identified through integrated analysis. The study identifies core genes associated with high-density lipoprotein and hormone secretion. These genes provide insights into the mechanisms through which BPA may cause hormonal imbalances. Furthermore, the study suggests that a complex exposure of BPA, BPS, and BPF can exerts different effects than BPA alone, pronounced effects on the thyroid and reproductive organs, even though individual concentrations were below the no-observed-adverse-effect-level. It highlights the potential cumulative impact of endocrine disrupting chemicals in the body.
2024-03-08 | GSE259227 | GEO
Project description:Aims Structural analogues of bisphenol A (BPA), including BPS and BPF, are emerging environmental toxicants as their presence in the environment is rising since new regulatory restrictions were placed on BPA-containing infant products. The adipogenesis-enhancing effect of bisphenols may explain the link between human exposure and metabolic disease; Methods Adipose-derived progenitors were isolated from mice and exposed to various concentrations of BPS, BPA or BPF before induction of adipogenesis. RNAseq in BPS-exposed progenitors revealed modulation in redox pathways. The role of reactive oxygen species (ROS) was assessed by measuring the degree of adipogenesis in the presence or absence of antioxidants. ROS production and mitochondria function were determined by fluorescent assays. Fat mass was measured by TD-NMR in adult mice exposed to BPS during in utero establishment of the adipocyte progenitor pool, and in adult mice exposed to BPS after weaning. however, underlying molecular pathways remain unresolved. Results Exposure of progenitors to BPS, BPF, BPA or ROS generators enhanced lipid droplet formation and expression of adipogenic markers after induction of differentiation. ROS was higher in bisphenol-exposed cells, while co-treatment with antioxidants attenuated adipogenesis and abolished the effect of BPS. There was a loss of mitochondria membrane potential in BPS-exposed cells and mitochondria-derived ROS contributed to potentiation of adipogenesis by BPS and its analogues. Male mice exposed to BPS during gestation had higher adiposity, while postnatal exposure had no impact on adiposity in either sex. ROS act as signaling molecules in the regulation of adipocyte differentiation and mediate bisphenol-induced potentiation of adipogenesis.
2022-09-23 | GSE213781 | GEO
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.
2022-10-14 | PXD035325 | Pride
Project description:The debate about possible adverse effects of bisphenol A (BPA) has been ongoing for decades and bisphenol-F (BPF) and -S (BPS) have been suggested as “safer” alternatives. In the present study we used hepatocyte-like cells (HLC) derived from the human embryonic stem cell lines Man12 and H9 to compare the three bisphenol derivatives. Stem cell-derived progenitors were produced using an established system, and, during their transition to HLCs, they were exposed to BPA, BPF and BPS for 8 days. Subsequently, we examined cell viability, inhibition of cytochrome P450 (CYP) activity, and genome-wide RNA profiles. Sub-cytotoxic, inhibitory concentrations (IC50) of CYP3A were 20, 9.5 and 25 µM for BPA, BPF and BPS in Man12 derived HLCs, respectively. The corresponding concentrations for H9-derived HLCs were 19, 29 and 31 µM. These IC50 concentrations were used to study global expression changes in this in vitro study and are higher than unconjugated BPA in serum of the general population. A large overlap of up- as well as down- regulated genes induced by the three bisphenol derivatives was seen. This is at least 28-fold higher compared to randomly expected gene expression changes. Moreover, highly significant correlations of expression changes induced by the three bisphenol derivatives were obtained in pairwise comparisons. Dysregulated genes were associated with reduced metabolic function, cellular differentiation, embryonic development, cell survival and apoptosis. In conclusion, no major differences in cytochrome inhibitory activities of BPA, BPF and BPS were observed and gene expression changes showed a high degree of similarity.
2020-10-29 | GSE160360 | GEO
Project description:Since initial regulatory action in 2010 in Canada, bisphenol A (BPA) has been progressively replaced by structurally related alternative chemicals. Unfortunately, many of these chemicals are data-poor, limiting toxicological risk assessment. We used high-throughput transcriptomics to evaluate potential hazards and compare potencies of BPA and 15 BPA alternative chemicals in cultured breast cancer cells. MCF-7 cells were exposed to BPA and 15 alternative chemicals (0.0005 – 100 µM) for 48 hrs. TempO-Seq sequencing (BioSpyder Inc.) was used to examine general toxicological effects and estrogen receptor alpha (ERα)-associated transcriptional changes. Benchmark concentration (BMC) analysis was conducted to identify two global transcriptomic points of departure (tPODs): (a) the lowest pathway median gene BMC and (b) the 25th lowest rank-ordered gene BMC. ERα activation was evaluated using a published transcriptomic biomarker and an ERα-specific tPOD was derived. Genes fitting BMC models were subjected to upstream regulator and canonical pathway analysis in Ingenuity Pathway Analysis. Biomarker analysis identified BPA and eight alternative chemicals as ERα active. Global and ERα tPODs produced highly similar potency rankings with BPAF as the most potent chemical tested, followed by BPA, BPC, 4,4’-BPF, BPAP, BPS, BADGE, 2,4’-BPF, Pergafast201®, D-8, 2,4’-BPS, TGSA, and BPS-MAE. Further, BPA and transcriptionally active alternative chemicals enriched similar gene sets associated with increased cell division and cancer-related processes. These data provide support for future read-across applications of transcriptomic profiling for risk assessment of data-poor chemicals and suggest that several BPA alternative chemicals may cause hazards at similar concentrations to BPA.
2022-08-18 | GSE211183 | GEO
Project description:Three different cell lines (MCF-7, MCF-10A, MCF-12A) were exposed to varying concentrations of BPA, BPA-analogues, pendimethalin and pendimethalin formulation.
2022-10-25 | GSE182963 | GEO