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Replacement Per and Polyfluoroalkyl Substance GenX Induces Fibroinflammatory Gene Expression in Primary Human Hepatocytes

ABSTRACT: Replacement Per and Polyfluoroalkyl Substance GenX Induces Fibroinflammatory Gene Expression in Primary Human Hepatocytes

PROVIDER: PRJNA777621 | ENA |

REPOSITORIES: ENA

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Replacement Per and Polyfluoroalkyl Substance GenX Induces Fibroinflammatory Gene Expression in Primary Human Hepatocytes

Project description:To goal of this study was to determine the effects of GenX on freshly isolated primary human hepatocytes (PHH).

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Per- and Polyfluoroalkyl Substance Exposure Combined with High-Fat Diet Supports Prostate Cancer Progression

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Identifying Human Specific Adverse Outcome Pathways of Per- and Polyfluoroalkyl Substances Using Liver-Chimeric Humanized Mice

Project description:We investigated the effects of per- and polyfluroralkyl substance exposure on FRG liver-chimeric humanized mice on a C57Bl/6 background. These PFAS included PFOA, PFOS, and GenX. These mice were exposed to water ad libitum for 28 days to reach human relevant serum concentrations. We then performed RNA-Sequencing on isolated whole liver lysate to determine differentially expressed genes.

2023-07-14 | GSE208636 | GEO

Fetal and maternal liver expression post gestational exposure to perfluorooctanoic acid (PFOA) or hexafluoropropylene oxide-dimer acid (HFPO-DA or GenX) in CD-1 mice

Project description:Multiple per- and polyfluoroalkyl substances (PFAS) have been associated with adverse liver outcomes in adult humans and toxicological models, but effects on the developing liver or biologic pathways involved are not known. We performed whole-transcriptome gene expression analysis to investigate the molecular mechanisms of liver toxicity in the dam and female fetuses after exposure to two different PFAS, perfluorooctanoic acid (PFOA) and its replacement, hexafluoropropylene oxide-dimer acid (HFPO-DA, commonly referred to as GenX).

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Per- and Polyfluoroalkyl Substance Exposure Combined with High-Fat Diet Supports Prostate Cancer Progression

Project description:Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals utilized in various industrial settings, and include products such as flame retardants, artificial film-forming foams, cosmetics, non-stick cookware among others. Epidemiological studies suggest a link between increased blood PFAS levels and prostate cancer incidence, but the mechanism through which PFAS impact cancer development is unclear. To investigate the link between PFAS and prostate cancer, we evaluated the impact of metabolic alterations resulting from a high-fat diet combined with PFAS exposure on prostate tumor progression. Our studies are the first in the field to provide new and clinically relevant insights regarding novel metabolic and epigenetic states and support future development of effective preventative and therapeutic strategies for PFAS-induced prostate cancers. Our findings enhance understanding of how PFAS synergize with high-fat diets to contribute to prostate cancer development and establish an important basis to mitigate PFAS exposure.

2021-12-01 | GSE185183 | GEO

Differential Developmental Neurotoxicity and Tissue Uptake of the Per- and Polyfluoroalkyl Substance Alternatives, GenX and PFBS.

Project description:Per- and polyfluoroalkyl substances (PFAS) are a class of synthetic chemicals with several applications. Multiple adverse health effects are reported for longer carbon chain (≤C8) PFAS. Shorter carbon chain PFAS, [e.g., hexafluoropropylene oxide dimer acid (HFPO-DA; GenX) and perfluorobutanesulfonic acid (PFBS)] were introduced as alternatives. Past studies indicate that longer-chain PFAS are neurotoxic targeting the dopamine pathway, but it is not known if shorter-chain PFAS act similarly. This study aimed to evaluate developmental neurotoxicity and tissue uptake of GenX and PFBS using the zebrafish (Danio rerio). First, acute toxicity was assessed by measuring LC50 at 120 h postfertilization (hpf). Body burden was determined after embryonic exposure (1-72 hpf) to sublethal concentrations of GenX or PFBS by LC-ESI-MS/MS. Locomotor activity using a visual motor response assay at 120 hpf and dopamine levels at 72 hpf was assessed after embryonic exposure. PFBS was more acutely toxic and bioaccumulative than GenX. GenX and PFBS caused hyperactivity at 120 hpf, but stronger behavioral alterations were observed for PFBS. An increase in whole organism dopamine occurred at 40 ppb of GenX, while a decrease was observed at 400 ppb of PFBS. Differences detected in dopamine for these two PFAS indicate differential mechanisms of developmental neurotoxicity.

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Project description:Per- and Polyfluoroalkyl Substances Cause Changes in MicroRNA Expression within Extracellular Vesicles

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Environmentally relevant concentrations of individual per- and polyfluoroalkyl substances (PFAS) and a PFAS mixture impact proliferation and gene transcription in a human myometrial cell line.

Project description:Per- and polyfluoroalkyl substances (PFAS) are environmental contaminants of concern due to their persistence and potential adverse health effects. Epidemiological studies have linked PFAS with an increased risk of uterine diseases including fibroids however, the mechanisms involved remain to be elucidated. This study investigated the effects of individual PFAS, including long-chain “legacy” PFAS [perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS)] and short-chain “alternative” PFAS compounds [undecafluoro-2-methyl-3-oxahexanoic acid (GENX/HFPO-DA), perfluorobutanesulfonic acid (PFBS)], as well as a mixture of these chemicals on the function and transcriptome of an immortalized human myometrial cell line (UT-TERT). UT-TERT cells exposed to individual PFAS displayed increased cell viability and proliferation. Flow cytometry analysis revealed that PFOS and the PFAS mixture altered cell cycle progression. Migration assays demonstrated that PFOS and the PFAS mixture significantly enhanced UT-TERT cell migration. Gap junction intercellular communication (GJIC) was impaired following PFOA, PFBS, and PFAS mixture exposure, indicating potential disruptions in cell-to-cell communication within the uterine environment. Transcriptomic analysis using RNA-seq identified substantial changes in gene expression after exposure to environmentally relevant levels of individual PFAS and PFAS mixture. Pathway analysis revealed common molecular pathways associated with PFAS exposure, including Cell-to-Cell Signaling, Lipid Metabolism, and Cell Death and Survival, while other pathways were unique to specific PFAS. These findings highlight the multifaceted effects of PFAS on myometrial cells, providing insights into the potential mechanisms underlying PFAS-associated health risks. Further research is necessary to elucidate the long-term implications of PFAS exposure on uterine function and overall reproductive health.

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Project Genx-CDI

Project description:Project Genx-CDI_Raw sequence reads

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