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ABSTRACT:
PROVIDER: PRJNA908883 | ENA |
REPOSITORIES: ENA
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Project description:Gene expression data from short-term in vivo studies shows efficacy in quantifying concentration-dependent effects that inform toxicity outcomes, particularly for chemicals with limited toxicity data such as Per- and Polyfluoroalkyl Substances (PFAS). Automated behavioral assessments, at non-teratogenic concentrations reveal perfluorohexane-1-sulfonate (PFHxS) exposure causes hyperactivity in larval zebrafish (6 days post fertilization (dpf)) during the light phase of the light:dark assay compared to 0.4% dimethylsulfoxide (DMSO) vehicle control. To identify key events that drive this abnormal behavior, zebrafish embryos were exposed to 7.87-25.1 μM PFHxS or 0.4% DMSO, and RNA was isolated from pooled head tissue collected at 4 and 5 dpf, before the onset of hyperactivity, for RNA-sequencing (NextSeq 500). Differentially expressed genes (DEGs) were identified using Gene Specific Analysis (Partek Flow, St. Louis, MO) and mapped to human orthologs for pathway analyses to inform modes of action.
2023-05-08 | GSE190009 | GEO
Project description:In a recent egg injection study, we showed that in ovo exposure to perfluorohexane sulfonate (PFHxS) affects the pipping success of developing chicken (Gallus gallus domesticus) embryos. We also found evidence of thyroid hormone (TH) pathway interference at multiple levels of biological organization (i.e. somatic growth, mRNA expression and circulating free thyroxine levels). Based on these findings, we hypothesize that PFHxS exposure interferes with TH-dependent neurodevelopmental pathways. The present study investigates global transcriptional profiles of cerebral cortex tissue from chicken embryos following exposure to a solvent control, 890 or 38,000 ng PFHxS/g egg (n=4-5 per group); doses which lead to the adverse effects above. PFHxS significantly alters the expression (≥1.5-fold, p≤0.001) of 11 transcripts at the low dose (LD; 890 ng/g) and 101 transcripts at the high dose (HD; 38,000 ng/g). Functional enrichment analysis shows that PFHxS affects genes involved in tissue development and morphology, cellular assembly and organization, and cell-to-cell signalling. Pathway and interactome analyses suggest that genes may be affected through several potential regulatory molecules, including integrin receptors, myelocytomatosis viral oncogene and CCAAT/enhancer binding protein. This study identifies key functional and regulatory modes of PFHxS action involving TH-dependent and -independent neurodevelopmental pathways. Some of these TH-dependent mechanisms that occur during embryonic development include tight junction formation, signal transduction and integrin signaling, while TH-independent mechanisms include gap junction intercellular communication. Reference Design. Reference = pool of equal parts of all control and treated samples. Control groups and 2 treatment groups. Control samples were chicken embryonic cerebral cortex exposed DMSO only (solvent). Treatments were: chicken embryonic cerebral cortex exposed to 890 ng/g PFHxS (LD) and 38,000 ng/g PFHxS (HD).
2012-04-17 | E-GEOD-37339 | biostudies-arrayexpress
Project description:In a recent egg injection study, we showed that in ovo exposure to perfluorohexane sulfonate (PFHxS) affects the pipping success of developing chicken (Gallus gallus domesticus) embryos. We also found evidence of thyroid hormone (TH) pathway interference at multiple levels of biological organization (i.e. somatic growth, mRNA expression and circulating free thyroxine levels). Based on these findings, we hypothesize that PFHxS exposure interferes with TH-dependent neurodevelopmental pathways. The present study investigates global transcriptional profiles of cerebral cortex tissue from chicken embryos following exposure to a solvent control, 890 or 38,000 ng PFHxS/g egg (n=4-5 per group); doses which lead to the adverse effects above. PFHxS significantly alters the expression (≥1.5-fold, p≤0.001) of 11 transcripts at the low dose (LD; 890 ng/g) and 101 transcripts at the high dose (HD; 38,000 ng/g). Functional enrichment analysis shows that PFHxS affects genes involved in tissue development and morphology, cellular assembly and organization, and cell-to-cell signalling. Pathway and interactome analyses suggest that genes may be affected through several potential regulatory molecules, including integrin receptors, myelocytomatosis viral oncogene and CCAAT/enhancer binding protein. This study identifies key functional and regulatory modes of PFHxS action involving TH-dependent and -independent neurodevelopmental pathways. Some of these TH-dependent mechanisms that occur during embryonic development include tight junction formation, signal transduction and integrin signaling, while TH-independent mechanisms include gap junction intercellular communication.
2012-04-18 | GSE37339 | GEO
Project description:PFAS are persistent man-made chemicals considered to be emerging pollutants, with PFOA, PFOS, and PFHxS having associations with liver toxicity and steatosis. PFOA, PFOS, and PFHxS can undergo placental/lactational transfer, however, little is known about the impact of PFAS mixtures during the developmental window, nor maternal diet on PFAS adverse effects. It was hypothesized that gestational/lactational PFAS exposure would alter the pup liver proteome. The work herein evaluated the liver proteome in offspring, identifying potential biochemical/signaling pathways altered via maternal PFAS exposure. Timed-pregnant CD-1 dams were fed a standard chow or 60% kcal high-fat diet. From GD1 until PND20, dams were orally gavaged daily with either 0.5% Tween 20, individual PFOA, PFOS, PFHxS at 1 mg/kg, or a mixture (1 mg/kg each, totaling 3 mg/kg). Livers were collected from PND21 offspring and SWATH-MS pro-teomics was performed. IPA analysis revealed disease and biological function pathways involved in liver damage, xenobiotics, and lipid regulation were modulated by PFAS exposure in the PND21 liver: lipid transport, storage, oxidation, and synthesis, xenobiotic metabolism and transport, liver damage and inflammation, and fatty acid metabolism, oxidation and transport. This indicates the pup liver proteome is altered via maternal exposure and predisposes the pup to metabolic dysfunctions.
2024-05-09 | PXD052106 | Pride
Project description:Obesity is a complex disease with many causes, including a possible role of environmental chemicals. Perfluorohexane sulfonate (PFHxS) is one of many per- and polyfluoroalkyl substances (PFASs) frequently detected in humans and it is a suspected obesogenic compound. We examined the potential long-term effects of PFHxS on metabolic parameters in rats after developmental exposure to 0.05, 5 or 25 mg/kg bw/day, with or without co-exposure to a background mixture of 12 endocrine disrupting chemicals (EDmix). Both male and female offspring showed signs of lower birth weight following intrauterine exposure. Female offspring exposed to both PFHxS and EDmix showed increased body weight in adulthood. Furthermore, the retroperitoneal fat pad was larger in these female offspring when compared to those exposed to EDmix alone. An attempt to detect putative molecular markers in the fat tissue by performing whole transcriptome profiling resulted in no significant changes between groups and there were no significant effects on plasma leptin levels in exposed females. These results show that early life exposure to endocrine disrupting chemicals can influence body weight later in life, but the effect is not necessarily reflected in changed gene expression in the fat tissue.
2020-07-07 | GSE146489 | GEO
Project description:Non-alcoholic fatty liver disease (NAFLD) is most prevalent form of liver disease, affecting over 30% of Americans. Perfluoroalkyl substances (PFAS) represent a family of environmental toxicants that have infiltrated the living world. This study explores diet-PFAS interactions and their potential role in the increasing global incidence of NAFLD. Male C57BL/6 mice were fed with either a low-fat diet (11% kcal from fat) or a high fat (58% kcal from fat) high carbohydrate (42g/L) diet with or without PFOS or PFHxS in feed (0.0003% w/w) for 29 weeks. Proteomic, lipidomic, and gene expression measurement techniques were utilized to explore mechanistic pathways. With administration of a high fat high carbohydrate (HFHC) diet, PFOS and PFHxS augmented macrovesicular steatosis, indicative of fatty liver. There was a clear shift in the lipidome of the serum phosphatidylcholines, phosphatidylethanolamines, and triglycerides with PFAS exposure. Finally, chain length exerted significant influence on tissue partitioning and the resulting hepatic gene and protein signatures of PFHxS and PFOS in vivo.
2020-09-15 | PXD015976 | Pride
Project description:This study aimed to assess PFAS distribution and lung proteome changes in CD-1 offspring after gestational and lactational exposure to PFOS, PFOA, PFHxS, or a PFAS mix. A secondary aim was to evaluate how maternal exposure to a high fat diet (HFD) affected the latter endpoints. Pregnant CD-1 mice received PFOA, PFOS, PFHxS (1 mg/kg), a PFAS mix (1 mg/kg each), or vehicle. Dams were fed standard diet (SD) or high fat diet (HFD), and PFAS were administered from gestation day 1 to postnatal day 20. At PND 21, lung PFAS concentration was measured using LC-MS/MS, and proteomic analysis was conducted. Results from LC-MS/MS analysis showed a significant overall difference in PFOS, PFOA, and PFHxS levels and the treatment groups with PFHxS concentration were significantly higher compared to PFOS and PFOA. Proteomic analysis determined female pups exposed to maternal HFD Mix (Mix HFD female) and PFOS (PFOS HFD female) had the most differentially expressed proteins followed by PFOS SD male, Mix SD female, and Mix SD male. Canonical pathways like EIF2 signaling, mTOR signaling, and mitochondrial dysfunction were differentially modulated. This study provides insights into PFAS distribution, the molecular mechanism, biomarkers on the neonatal lung in animal models following perinatal exposure.
2023-12-06 | MSV000093587 | MassIVE
Project description:PPARα-null and wild-type male mice treated with PFHxS or PFNA PPARα-null and wild-type male mice at 6-9 months of age were dosed by gavage for 7 consecutive days with either 0, 3, or 10 mg/kg PFHxS, or 1 or 3 mg/kg PFNA (#394459, Sigma-Aldrich, St, Louis, MO) in water. PFHxS was kindly provided by 3M Corp (St. Paul, MN). Four biological replicates consisting of individual animals were included in each dose group. Dose levels reflected exposures that produce hepatomegaly in adult mice without inducing overt toxicity.
2014-03-17 | E-GEOD-55756 | biostudies-arrayexpress
Project description:The per-and polyfluoroalkyl substances (PFAS) are of significant global concern due to their highly ubiquitous and persistent nature, bioaccumulation in organisms, and potential toxicity. The aquatic environment is known as an important sink for PFAS resulting in high concentrations in aquatic organisms. However, little is known about the developmental windows of sensitivity in which the PFAS chemicals are biologically active, in addition to the toxicity endpoints that best reflect chemical hazard. In this study, zebrafish (Danio rerio) were exposed to a 0.33% DMSO vehicle control, 1uM chlorpyrifos (CAS 2921-88-2) positive control, and eight concentrations (0-100 uM, half-log dilutions) of three environmentally relevant PFAS compounds in concentration-response: PFOS (CAS 1763-21-1), PFOA (CAS 45285-51-6), and PFHxS (CAS 355-46-4). There was also a group of unexposed zebrafish aliquoted from a single pool into all exposure plates to serve as a quality assurance measure. The goal of this study was to generate transcriptomic point of departure (tPOD; a benchmark dose/concentration -based treatment level below which a concerted gene expression response is not observed) estimates for zebrafish exposed to PFAS compounds as a health protective exposure level for risk assessment. Through the use of short-term embryo/larval plate-based high-throughput toxicity tests, tPODs were determined across seven distinct developmental windows (6-24 hours post fertilization (hpf), 6-48 hpf, 24-48 hpf, 6-120 hpf, 24-120 hpf, 48-120 hpf, 96-120 hpf) to assess how common experimental design variables (e.g., different exposure durations, exposure at different developmental stages) affect point of departure estimates.
2024-08-28 | GSE242402 | GEO
Project description:To explore the transcriptional effects of aromatase inhibitors on sex differentiation of zebrafish, we exposed 3-month-old zebrafish (AB strain) to the third generation aromatase inhibitor Exemestane (CAS: 107868-30-4) and characterized transcript abundance among testes and ovaries after 32 days of drug exposure. After the drug treatment, we dissected zebrafish gonads, isolated polyA+ RNA and performed high-throughput RNA-Seq analysis.
2019-12-07 | GSE123439 | GEO