Environmentally relevant exposure to TBBPA and its analogues may not drastically affect human early cardiac development
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA795182 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17469100.fastq.gz | Fastqsanger.gz | |||
| SRR17469101.fastq.gz | Fastqsanger.gz | |||
| SRR17469102.fastq.gz | Fastqsanger.gz | |||
| SRR17469103.fastq.gz | Fastqsanger.gz | |||
| SRR17469104.fastq.gz | Fastqsanger.gz |
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Project description:Tetrabromobisphenol A (TBBPA) and its substitutes and derivatives have been widely used as halogenated flame retardants (HFRs), in the past few decades. As a consequence, these compounds are frequently detected in the environment, as well as human bodily fluids, especially umbilical cord blood and breast milk. This has raised awareness of their potential risks to fetuses and infants. In this study, we employed human embryonic stem cell differentiation models to assess the potential developmental toxicity of six TBBPA-like compounds, at human relevant nanomolar concentrations. To mimic early embryonic development, we utilized embryoid body-based 3D differentiation in presence of the six HFRs. Transcriptomics data showed that HFR exposure over 16 days of differentiation only interfered with the expression of a few genes, indicating those six HFRs may not have specific tissue/organ targets during embryonic development. Nevertheless, further analyses revealed that some cardiac-related genes were dysregulated. Since the heart is also the first organ to develop, we employed a cardiac differentiation model to analyze the six HFRs' potential developmental toxicity in more depth. Overall, HFRs of interest did not significantly disturb the canonical WNT pathway, which is an essential signal transduction pathway for cardiac development. In addition, the six HFRs showed only mild changes in gene expression levels for cardiomyocyte markers, such as NKX2.5, MYH7, and MYL4, as well as a significant down-regulation of some but not all the epicardial and smooth muscle cell markers selected. Taken together, our results show that the six studied HFRs, at human relevant concentrations, may impose negligible effects on embryogenesis and heart development. Nevertheless, higher exposure doses might affect the early stages of heart development.
2023-02-02 | GSE193176 | GEO
Project description:The aim of this study was to identify TBBPA-degrading organisms in a complex microbial community by a metagenome-based functional metaproteomic approach, using protein-based stable isotope probing (protein-SIP). Firstly, the degradation kinetics were evaluated in order to simulate the decrease of residual mass of the labelled compound based on experimental data. In sequence, a metagenome was generated, and biomass was collected in different time-points for protein-SIP in incubations with 13C-TBBPA. This approach allowed for the identification organisms assimilating labelled carbon from the cometabolic degradation of a micropollutant.
2022-09-12 | PXD030335 | Pride
Project description:3,3’,5.5’-Tetrabromobisphenol A (TBBPA) is a widely used brominated flame-retardant utilized in the production of electronic devices and plastic paints. The objective of this study is to use zebrafish as a model and determine the effects of TBBPA exposure on early embryogenesis. We initiated TBBPA exposures (0, 10, 20 and 40μM) at 0.75 h post fertilization (hpf) and monitored early developmental events such as cleavage, blastula and epiboly that encompass maternal-to-zygotic transition (MZT) and zygotic genome activation (ZGA). Our data revealed that TBBPA exposures induced onset of developmental delays by 3 hpf (blastula). By 5.5 hpf (epiboly), TBBPA-exposed (10-20 μM) embryos showed concentration-dependent developmental lag by up to 3 stages or 100% mortality at 40 μM. Interestingly, while continued 0.75- 48 hpf TBBPA exposures (10 μM) led to severely deformed embryos, replacing exposure solution with chemical-free media at 6 hpf mitigated this effect, with 100% normal embryos at 48 hpf. To examine the genetic basis of TBBPA-induced delays, we conducted mRNA-sequencing on embryos exposed to 0 or 40 μM TBBPA from 0.75 hpf to 2, 3.5 or 4.5 hpf. Read count data showed that while TBBPA exposures had no overall impacts on maternal or maternal-zygotic genes, collective read counts for zygotically activated genes were lower in TBBPA treatment at 4.5 hpf compared to time-matched controls, suggesting that TBBPA delays ZGA. Gene ontology assessments for both time- and stage-matched differentially expressed genes revealed TBBPA-induced inhibition of chromatin assembly- a process regulated by histone modifications. Since acetylation is the primary histone modification system operant during early ZGA, we hypothesized that TBBPA inhibits histone acetylation, resulting in lack of open chromatin within promoters of zygotic genes and delaying ZGA. Therefore, we co-exposed embryos to 20 μM TBBPA and 100 μM N-(4-Chloro-3-(trifluoromethyl)phenyl)-2-ethoxybenzamide (CTB) -a histone acetyltransferase activator that promotes histone acetylation- and showed that TBBPA-CTB co-exposures from 0.75- 3 hpf significantly reversed TBBPA-only developmental delays, suggesting that TBBPA-induced phenotypes are indeed driven by repression of histone acetylation. Collectively, our work demonstrates that TBBPA disrupts ZGA and early developmental morphology, potentially by inhibiting histone acetylation. Future studies will focus on mechanisms of TBBPA-induced chromatin modifications.
2024-08-31 | GSE262783 | GEO
Project description:We evaluated the hepatic developmental toxicity of TBBPA/TBBPS/TCBPA with a human embryonic stem cells (hESC) system. We found that TBBPA/TBBPS/TCBPA might adversely affect human hepatocyte-like cells specification from hESCs via mainly impairing definitive endoderm specifications, suggesting the early stages of embryonic development are susceptible to the three compounds.
2020-04-29 | GSE129412 | GEO
Project description:Vertebrate eye devlopment is partially regulated by thyroid hormones. TBBPA is a chemical that interacts with thyroid receptors. We investigated the effects of TBBPA on eye development of zebrafish. We expected TBBPA exposure to cause transcriptional changes of visual-system-related genes, which find their phenotypic anchoring in eye malformations and dysfunction, as observed in our previous studies. Additionally, the reversibility of effects after recovery in clean water for three days was investigated.
2019-05-09 | GSE121336 | GEO
Project description:Halogenated flame retardants (HFRs) Tetrabromobisphenol A (TBBPA), Tetrabromobisphenol S (TBBPS) and Tetrachlorobisphenol (TCBPA) are wildly applied in manufacturing industry to improve the fire safety of the products. Recent reports demonstrated that TBBPA, TBBPS and TCBPA can be detected in pregnant women serum at nanomolar-level. Considering TBBPA have also been detected in the cord serum and the structural similarity of the 3 HFRs, it is necessary to pay attention to their development toxicity. Liver is the important detoxic organ but also target of TBBPA since it has been demonstrated that TBBPA exposure lead to increased liver weight in mouse and rat. So the developmental hepatic toxicity of the 3 HFRs were studied in this current research with the transcriptomic and human embryonic stem cells hepatic differentiation based toxicity evaluation system. A hepatic differentiation specific lineage development map and cell lineage - gene expression annotations were made and used for easily assessing the lineage alternations caused by toxicant treatment. Together with GO and KEGG analysis, this study mainly demonstrated that, the 3 HFRs have many common disruptive effect on hepatic differentiation, while only TCBPA significantly inhibited hepatic differentiation. The up-regulation of genes related to cell cycle and FGF10 signaling pathway at relatively late stage of hepatic differentiation indicates the proliferation of hepatoblasts were promoted by the 3 HFRs, likely via up-regulating the FGF10 signaling pathway. The proliferating promoting effect may partly explain why liver gain weight in rodents exposed to TBBPA.
2023-04-03 | GSE148518 | GEO
Project description:We use a larval zebrafish model to assess the transcriptomic alterations caused by sub-phenotypic concentrations of two endocrine disrupting drugs: BPA and TBBPA.
2024-08-08 | GSE240125 | GEO
Project description:Numerous studies report active pharmaceutical compounds detected in both wastewater effluent and surface waters. Exposure to statin drugs in general, and atorvastatin in particular, is likely to be a concern. We hypothesized that chronic exposure to low concentrations of atorvastatin in water would result in an adverse effect on production of steroids regulating growth and development of the model amphibian Xenopus laevis. To assess the potential for impacts we used three experimental assays. The FETAX assay was used to evaluate the effects of a range of doses of atorvastatin on developing embryos. A 60 day metamorphosis assay assessed the effects of aqueous atorvastatin exposure at environmentally concentrations on metamorphosing tadpoles. A 60 day chronic flow-through exposure evaluated the effects of chronic low concentrations of atorvastatin on adults. The data from the FETAX assay confirmed uptake, activity, and effect of atorvastatin in X. laevis tadpoles. The results of the 60-day flow-through exposure on metamorphosing tadpoles showed significant evidence of altered cholesterol biosynthesis. The dose-dependent increase in cyp19a1 expression also indicated that the steroidogenesis pathway was affected. The RNAseq analysis confirmed that exposure to environmentally relevant concentrations of atorvastatin does cause significant alterations to global transcriptional profiles in a manner consistent with dysregulation of the cholesterol biosynthesis pathway, both through the downregulation of many genes involved in that pathway, but also in the impacts to other, related pathways. The qPCR data for both adult males and adult females indicated only slight changes in expression with the exception that hmgcr was significantly downregulated in males, and cyp3a4 expression was significantly downregulated in females. The data we present here indicated that chronic exposure to environmentally relevant concentrations of atorvastatin does have the potential to impact early life stage frogs, particularly by altering expression of genes involved in critical molecular pathways.
2023-07-07 | GSE236279 | GEO
Project description:Tetrabromobisphenol A (TBBPA) biodegradation in acidogenic systems: one step further on where and who
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