PBDE-47 and PBDE mixture (DE-71) toxicities and liver transcriptomic changes at PND 22 after in utero/postnatal exposure in the rat.
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PROVIDER: PRJNA512003 | ENA |
REPOSITORIES: ENA
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Project description:Test articles used: DE-71 (Pentabromodiphenyl Ether Mixture [Technical Grade), CAS Number 32534-81-9, DTXSID2024246); PBDE-47 (CAS Number 5436-43-1); PB (Phenobarbital, CAS Number 50-06-6 ); PCB (PCB126, CAS Number 57465-28-8)
2019-01-05 | GSE124431 | GEO
Project description:Liver gene transcripts patterns were used to characterize toxicity from exposure to polybrominated diphenyl ethers (PBDEs), flame retardant components. In this study, Wistar Han dams were exposed by gavage to the PBDE mixture (DE71) starting at gestation day 6 (GD 6) and continuing to weaning on postnatal day 21 (PND 21). Offspring from the dams began PBDE direct dosing on PND 12 and were dosed daily through PND 21. After weaning, they were dosed 5 days per week for another 13 weeks. Liver samples were collected at PND 22 and week 13 for liver gene expression analysis and interrogated with the Affymetrix Rat Genome 230 2.0 Array. PBDE treatment induced 1,066 liver gene transcript changes in females and 1,200 transcriptional changes in males at PND 22 (false discovery rate (FDR) < 0.01), but only 263 liver transcriptional changes at 13 weeks in male rats (FDR <0.05). No significant differences in dose response were found between male and female pups. There were a total of 6 groups and 5x replication for each group, for 30 total samples that were analyzed. The groups were (1) pup-male-CTL, (2) pup-female-CTL, (3) pup-male-PBDE, (4) pup-female-PBDE, (5) rat-male-CTL, (6) rat-male-PBDE. We generated the following pairwise comparisons using R/maanova: malePups(PBDE vs CTL), femalePups(PBDE vs CTL), maleRats(PBDE vs CTL), CTLpups(male vs female), PBDEpups(male vs female). We also performed ANOVA test for SEX-by-DOSE (pups) and AGE-by-DOSE (males). For pups, genes with an FDR≤1% were selected; for rats, genes with FDR < 5% were selected.
2011-10-04 | E-GEOD-32156 | biostudies-arrayexpress
Project description:Pentabromodiphenyl ethers (PBDE) are found in human tissue, in household dust, and in the environment, and a particular concern is the potential for the induction of cancer pathways from these fat-soluble persistent organic pollutants. Only one PBDE cancer study has been conducted and that was for a PBDE mixture (DE-71). Because it is not feasible to test all PBDE congeners in the environment for cancer potential, it is important to develop a set of biological endpoints that can be used in short-term toxicity studies to predict disease outcome after long-term exposures. In this study, PBDE-47 was selected as the test PBDE congener to evaluate and compare toxicity to that of the carcinogenic PBDE mixture. The toxicities of PBDE-47 and the PBDE mixture were evaluated at PND 22 in Wistar Han rat (Crl: WI (Han)) pups after in utero/postnatal exposure (0, 0.1, 15, or 50 mg/kg; dams, GD6-21; pups, PND 12-PND 21; oral gavage daily dosing). By PND 22, PBDE-47 caused centrilobular hypertrophy and fatty change in liver, and reduced serum thyroxin (T4) levels; similar effects were also observed after PBDE mixture exposure. Transcriptomic changes in the liver included induction of cytochrome p450 transcripts and up-regulation of Nrf2 antioxidant pathway transcripts and ABC membrane transport transcripts. Decreases in other transport transcripts (ABCG5 & 8) provided a plausible mechanism for lipid accumulation, characterized by a treatment-related liver fatty change after PBDE-47 and PBDE mixture exposure. The benchmark dose calculation based on liver transcriptomic data was generally lower for PBDE-47 than for the PBDE mixture. The up-regulation of the Nrf2 antioxidant pathway and changes in metabolic transcripts after PBDE-47 and PBDE mixture exposure suggest that PBDE-47, like the PBDE mixture (NTP 2016, TR 589), could be a liver toxin/carcinogen after long-term exposure.
| S-EPMC6706773 | biostudies-literature
Project description:Liver gene transcripts patterns were used to characterize toxicity from exposure to polybrominated diphenyl ethers (PBDEs), flame retardant components. In this study, Wistar Han dams were exposed by gavage to the PBDE mixture (DE71) starting at gestation day 6 (GD 6) and continuing to weaning on postnatal day 21 (PND 21). Offspring from the dams began PBDE direct dosing on PND 12 and were dosed daily through PND 21. After weaning, they were dosed 5 days per week for another 13 weeks. Liver samples were collected at PND 22 and week 13 for liver gene expression analysis and interrogated with the Affymetrix Rat Genome 230 2.0 Array. PBDE treatment induced 1,066 liver gene transcript changes in females and 1,200 transcriptional changes in males at PND 22 (false discovery rate (FDR) < 0.01), but only 263 liver transcriptional changes at 13 weeks in male rats (FDR <0.05). No significant differences in dose response were found between male and female pups.
2011-10-05 | GSE32156 | GEO
Project description:Expression data from PBDE-47 and DE-71 treated rats at PND4
| PRJNA647874 | ENA
Project description:ER+ PDX (COH-SC31) were exposed to PBDE mixture for 1 weeks. RNA-sequencing analysis was performed to evalaute the gene expression changes.
2019-03-04 | GSE119587 | GEO
Project description:Brominated flame retardants (BFRs) are incorporated into consumer products to prevent flame propagation. These compounds leach into the domestic environment, resulting in chronic exposure and contamination. Pregnancy failure is associated with high levels of BFRs in human follicular fluid, raising serious questions regarding their impact on female fertility. Our goal was to elucidate effects of a mixture reflecting human follicular fluid levels of polybrominated flame retardants (PBDEs), the major class of BFRs, on an immortalized human granulosa cell line, the KGN cell line. We showed that cell viability was altered and oxidative stress was induced, as reflected by increased reactive oxygen species formation, at 20 µM of the PBDE mixture. Transcriptomic analysis revealed that several genes showing an altered expression after the PBDE treatment were involved in oxidative stress signaling pathways. Significant dose-dependent reduction of progesterone and estradiol levels was measured after PBDE treatment; expression of genes involved in steroid hormone metabolism, namely CYP1A1, was significantly affected by PBDEs. Treatment with the PBDE mixture also modified genes encoding for members of the transforming growth factor β superfamily like inhibins and cytokines, including the pro-inflammatory factor, interleukin-6 (IL6). Concentration of IL-6 in KGN cell culture media was consistently increased after treatment with the PBDE mixture. Our results clearly demonstrate that the PBDEs detected in human follicular fluid alter human granulosa cell functions by inducing oxidative stress, disrupting steroidogenesis and triggering an inflammatory response. This strengthens the fact that PBDEs are detrimental to ovarian functions and thus, to women’s reproductive health.
2016-05-25 | GSE77963 | GEO
Project description:To identify liver transcripts differentially expressed between control samples and animals exposed to PBDE-47, we collected RNA from male pups at postnatal day 4 (PND4) after the Wistar Han dams were exposed to 0, 0.1, 15, or 50 mg/kg PBDE-47. These samples were interrogated with the Affymetrix Rat Genome 230 2.0 GeneChip array. A total of 7, 50, and 149 gene transcripts were differentially expressed between control samples and 0.1, 15, and 50 mg/kg PBDE-47 (using a false discovery rate (FDR) threshold of 0.05). These transcripts were mapped to 2, 40, and 139 genes using Ingenuity Pathway Analysis.
2020-07-22 | GSE154912 | GEO
Project description:Affymetrix high-density oligonucleotide microarray analysis was performed to analyse hydroxylated polybrominated diphenyl ethers (OH-PBDE)-induced gene expression changes in H295R adrenocortical carcinoma cells. Cells were treated with growth medium in the presence or absence of 10 µM 2-OH-BDE47 or 2-OH-BDE85 for 24 hours before the gene expression changes were investigated. Experiment Overall Design: Gene expression changes in response to hydroxylated polybrominated diphenyl ethers (OH-PBDEs) were analysed by Microarray technology in H295R adrenocortical carcinoma cells. Cells were treated with 10 µM of 2-OH-BDE47 or 2-OH-BDE85 (or growth medium alone) for 24 hours before the OH-PBDE-induced gene expression changes were investigated. Control, 2-OH-BDE47- and 2-OH-BDE85-treated samples were collected from three independent experiments each.
2009-01-02 | E-GEOD-8588 | biostudies-arrayexpress
Project description:Polybrominated diphenyl ethers (PBDEs) are commonly used as flame retardants in a variety of commercial and household products. They have been detected in the environment and accumulate in mammalian tissues and fluids. PBDE toxicity is thought to be associated with endocrine disruption, developmental neurotoxicity and changes in fetal development. Although humans are exposed to PBDEs, our knowledge of the effects of PBDE metabolites on human cells with respect to health risk is insufficient. Two hydroxylated PBDEs (OH-PBDEs), 2-OH-BDE47 and 2-OH-BDE85, were investigated for their effects on cell viability/proliferation, DNA damage, cell cycle distribution and gene expression profiling in H295R adrenocortical carcinoma cells. We show that the two agents are cytotoxic in a dose-dependent manner only at micromolar concentrations, with 2-OH-BDE85 being more toxic than 2-OH-BDE47. However, no DNA damage was observed for either chemical, suggesting that the biological effects of OH-PBDEs occur primarily via non-genotoxic routes. Furthermore, no evidence of aryl hydrocarbon receptor (AHR)-mediated, dioxin-like toxicity was observed. Instead, we report that a micromolar concentration of OH-PBDEs induces transcriptional changes associated with endoplasmic reticulum stress and the unfolded protein response. We discuss whether OH-PBDE bioaccumulation could result in impairment of the adrenocortical secretory function.
2008-12-25 | GSE8588 | GEO