High-throughput transcriptomics screening of mixtures of BPA alternatives reveal additive effects in vitro
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PROVIDER: PRJNA1159318 | ENA |
REPOSITORIES: ENA
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Project description:Humans are regularly exposed to mixtures of BPA alternative chemicals through their diets, consumer products and other sources. Like BPA, many alternatives perturb nuclear hormone receptors and are considered endocrine disrupting chemicals. We used high-throughput transcriptomics (HTTr) to evaluate the potency and potential modes of action of seven mixtures of BPA alternatives, along with their 12 individual components, in MCF-7 breast cancer cells. Our primary aim was to explore whether alternatives present in mixtures act additively. MCF-7 cells were exposed to chemicals (0.001 – 50 µM) for 48 h in serum-free conditions and TempO-Seq (BioSypder Inc.) was used to determine global and estrogen receptor alpha (ERα)-specific transcriptomic changes. Transcriptomic points of departure were derived using benchmark concentration (BMC) modelling. We first identified the concentration at which global transcriptional activity was robustly altered. Then, a novel ERα transcriptomic biomarker was used to identify ERα agonists and model a predicted ERα activation point of departure. Mixtures modelling was employed to predict potency of BPA alternatives and test for additive effects in vitro. Ingenuity Pathway Analysis (IPA; Qiagen) was used to identify upstream regulators and canonical pathways from genes fitting BMCs. All seven mixtures had additive effects across all transcriptomic points of departure modelled. BPAF was the most potent individual chemical tested overall, followed by BPA and BPC. The ERα transcriptomic biomarker classified all mixtures as ERα activators along with several individual BPA alternatives. Pathway analysis revealed that all mixtures and most individual components perturbed similar upstream regulators and pathways, suggesting common modes of action. These data support the use of HTTr as part of new approach methodologies to assess the toxicological potency of mixtures in vitro.
2025-06-30 | GSE276869 | GEO
Project description:Bisphenol A (BPA), a widely used chemical in the production of plastics and epoxy resins, has garnered significant attention due to its association with adverse health effects, particularly its endocrine-disrupting properties. Regulatory measures aimed at reducing human exposure to BPA have led to a proliferation of alternative chemicals used in various consumer products. While these alternatives serve to reduce BPA exposure, concerns have arisen regarding their safety and potential toxicity as regrettable substitutes. Previous efforts have demonstrated that in vitro high-throughput transcriptomics (HTTr) studies can be used to assess the endocrine-disrupting potential of BPA alternatives, and this strategy produces transcriptomic points-of-departure (tPoDs) that are protective of human health when compared to the PODs from traditional rodent studies. In this study, we leveraged in vitro HTTr advancements to assess the toxicity of eleven data-poor legacy chemicals sharing structural similarities to BPA. Human breast cancer MCF-7 cells were exposed to BPA and 11 alternatives at concentrations ranging from (0.1 - 25 µM) to assess toxicity. Analysis of global transcriptomic changes and a previously characterized estrogen receptor alpha (ERα) biomarker signature revealed that 9/11 chemicals were bioactive. One of the chemicals (2,4’-Bisphenol A) activated the ERα biomarker at the same concentration as BPA (i.e., 4,4’-BPA) but was deemed to be more potent as it induced global transcriptomic changes at lower concentrations. These results are addressing data gaps in ongoing screening assessments to identify BPA alternatives with hazard potential and are helping to identify potential candidates to serve as safer alternatives.
2024-08-26 | GSE271332 | 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:Additive effect of multi-strain mixtures
| PRJEB71990 | ENA
Project description:Aim: Identify Ambra1-dependent regulation in melanoma development by comparing bulk RNA extracted from Ambra1-depleted (BPA-/-) mouse melanomas to Ambra1-wt (BPA+/+) melanomas.
2021-03-04 | GSE151134 | GEO
Project description:Adult female three-spined stickleback fish (Gasterosteus aculeatus) were exposed to 10 individual chemicals, 26 mixtures of these chemicals, or control conditions in a flow-through system for 4 days. Transcriptomics was performed on liver samples by microarray. The main aims were to determine molecular signatures induced by these chemicals in the three-spined stickleback, discover whether these persisted in chemical mixtures and identify non-additive molecular responses in chemical mixtures exposures.
2018-03-01 | E-MTAB-5581 | biostudies-arrayexpress
Project description:Bisphenol A (BPA) is an environmental endocrine disruptor which has been detected in almost all human bodies. Many studies have implied that BPA exposure is harmful to human health. Previous studies mainly focused on BPA effects on ER-positive cells. Genome-wide impact of BPA on gene regulation in ER-negative cells is unclear. In the present study, we performed RNA-seq to characterize BPA-induced gene regulation on ER-negative HEK 293 cells.
2014-10-10 | E-MTAB-1959 | biostudies-arrayexpress
Project description:The recent development of a custom cDNA microarray platform for one of thé standard organisms in aquatic toxicology, Daphnia magna, opened up new ways to mechanistic insights of toxicological responses. In this study, gene expression and (sub)organismal responses (Cellular Energy Allocation, growth) were assayed after short-term waterborne metal exposure. Microarray analysis of Ni-exposed daphnids revealed several affected functional gene classes, of which the largest ones were involved in different metabolic processes (mainly protein and chitin related processes), cuticula turnover, transport and signal transduction. Furthermore, genes involved in oxygen transport and heme metabolism (hemoglobin, δ-aminolevilunate synthase) were down-regulated. Applying a Partial Least Squares regression on nickel fingerprints and biochemical (sub)organismal parameters revealed a set of co-varying genes (hemoglobin, RNA terminal phosphate cyclase, a ribosomal protein and an “unknown” gene fragment). An inverse relationship was seen between the mRNA expression levels of different cuticula proteins and available energy reserves. In addition to the nickel exposure, daphnids were exposed to binary mixtures of nickel and cadmium or nickel and lead. Using multivariate analysis techniques, the mixture gene expression fingerprints (Ni2++Cd2+, Ni2++Pb2+) were compared to those of the single metal treatments (Ni2+, Cd2+, Pb2+). It was hypothesized that the molecular fingerprints of the mixtures would be additive combinations of the gene expression profiles of the individual compounds present in the mixture. However, our results clearly showed additionally affected pathways after mixture treatment (e.g. additional affected genes involved in carbohydrate catabolic processes and proteolysis), indicating interactive molecular responses which are not merely the additive sum of the individual metals. These findings, although indicative of the complex nature of mixture toxicity evaluation, underline the potential of a toxicogenomics approach in gaining more mechanistic information on the effects of single compounds and mixtures.
2009-02-27 | GSE13866 | GEO
Project description:Identification of differentially expressed genes in BPA-/- and BPA+/+ mouse melanomas.
| PRJNA634850 | ENA
Project description:Expression profiling analyses for 5 maize inbreds and 4 hybrids, chosen to represent diversity in genotypes and heterosis responses, revealed a correlation between genetic diversity and transcriptional variation. The majority of differentially expressed genes in each of the different hybrids exhibited additive expression patterns, and ~25% exhibited statistically significant non-additive expression profiles. Among the non-additive profiles, ~80% exhibited hybrid expression levels between the parental levels, ~20% exhibited hybrid expression levels at the parental levels and ~1% exhibited hybrid levels outside the parental range. These findings indicate that the frequencies of additive and non-additive expression patterns are very similar across a range of hybrid lines. Keywords: Genotype comparison series
2008-01-26 | GSE10236 | GEO