Effects of BPA, BPF and BPS treatments on mESC EB-based global and neural differentiations.
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ABSTRACT:
PROVIDER: PRJNA492233 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7881430.fastq.gz | Fastqsanger.gz | |||
| SRR7881440.fastq.gz | Fastqsanger.gz | |||
| SRR7881450.fastq.gz | Fastqsanger.gz | |||
| SRR7881460.fastq.gz | Fastqsanger.gz | |||
| SRR7881431.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: the goal of this study is to determine the changes in gene expression during EB differentiation after BPA, BPF and BPS treatments, as indications of potential developmental toxicity. Methods: Transcriptomics profiling for EB samples treated with 100 nM BPA, BPF, BPS or DMSO control at different time points were generated by RNA-seq, using a BGISEQ-500 platform. Reads were filtered and aligned to the reference genome with Bowtie2. Results: BPA, BPF and BPS disrupted many processes, during mESC global and neural differentiations, in very similar manners. In fact, analogous gene categories were differentially regulated by the three chemicals, at each time point, particularly the ones involved in cell-matrix and cell-cell adhesions, signal transduction pathways, and medical conditions such as cardiovascular diseases and cancer.
2019-09-30 | GSE120224 | 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:Over the past several years, replacement chemicals for bisphenol A have been manufactured and used as additives in sportswear, plastic bottles, food packaging, and in other products. More recently, replacement products for BPA are under investigation for toxicity, but there are little data on the potential for neurotoxicity. To address this gap, differentiated human SH-SY5Y cells were treated with a range of concentrations of BPS and BPF to better understand mechanisms of toxicity.
2024-04-27 | GSE217951 | GEO
Project description: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.
2021-07-19 | GSE153320 | 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: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: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: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.
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2024-03-08 | GSE259227 | GEO