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Effects of Polybrominated Diphenyl Ether (PBDE) Mixture on estrogen receptor positive (ER+) patient-derived tumor xenograft (PDX) model

ABSTRACT: ER+ PDX (COH-SC31) were exposed to PBDE mixture for 1 weeks. RNA-sequencing analysis was performed to evalaute the gene expression changes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE119587 | GEO | 2019/03/04

REPOSITORIES: GEO

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Effects of Polybrominated Diphenyl Ether (PBDE) Mixture on estrogen receptor positive (ER+) patient-derived tumor xenograft (PDX) model

Project description:Effects of Polybrominated Diphenyl Ether (PBDE) Mixture on estrogen receptor positive (ER+) patient-derived tumor xenograft (PDX) model

| PRJNA489668 | ENA

A Mixture Reflecting Polybrominated Diphenyl Ether (PBDE) Profiles Detected in Human Follicular Fluid Significantly Affects Steroidogenesis and Induces Oxidative Stress in a Human Granulosa Cell Line

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

reductive debromination of polybrominated diphenyl ethers by Dehalococcoides

Project description:Extensive use of polybrominated diphenyl ethers (PBDEs) has resulted in widespread environmental distribution and concerns remain about risks to human health and ecosystems from legacy PBDE contamination. Though bioremediation has been proven to be a cost-effective and efficient technology for treating halogenated pollutants in situ, application of bioremediation technologies at PBDE-contaminated sites is restricted by a lack of knowledge about functional PBDE-dehalogenating microbes. In the current study, we observed distinct PBDE-dehalogenation activity by three previously isolated Dehalococcoides mccartyi strains (CG1, CG4, and 11a5). PBDE debromination proceeded via distinct pathways in each D. mccartyi strain and involved previously characterized (TceA11a5, PcbA1, and PcbA4) and uncharacterized (11a5_e001) reductive dehalogenases (RDase), suggesting that this phenotype may be more widespread among the Dehalococcoides than is currently recognized.

2022-05-26 | PXD026932 | Pride