The Pollutant Perfluorohexane Sulfonate (PFHxS) Reduces Serum Thyroxine but Does Not Alter Thyroid Hormone Action in the Postnatal Rat Brain
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PROVIDER: PRJNA1093110 | ENA |
REPOSITORIES: ENA
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Project description:Per- and polyfluoroalkyl substances (PFAS) are surfactants utilized in an array of commercial products including nonstick cookware, stain resistant textiles, personal care products, and firefighting foam. Despite their widespread use, concerns regarding the safety of these compounds have been raised. One of the most reproducible effects of some PFAS is their ability to reduce serum thyroid hormones (THs) such as thyroxine (T4) and triiodothyronine (T3) in animal models. As THs are required for normal brain development, PFAS may also be developmental neurotoxicants. Here, we examine the endocrine and neurodevelopmental consequences of perfluorohexane sulfonate (PFHxS) exposure in pregnant, lactating, and developing rats, and compare its effects to the goitrogen propylthiouracil (PTU). We show that PFHxS dramatically reduces maternal serum T4, nearly equivalently to PTU (-55 and -51%, respectively). However, only PTU increases thyroid stimulating hormone (TSH). The lactational transfer of PFHxS is significant and reduces pup serum T4 across the postnatal period. However, only PTU drastically reduces brain THs. Evaluation of brain TH action by phenotyping, RNA-Sequencing, and quantification of radial glia cell morphology supports that PTU interrupts brain TH signaling while PFHxS has limited to no effect. Overall, these data show that PFHxS induces abnormal serum TH profiles in dams and pups; however, there were no indications of hypothyroidism in the postnatal brain. We suggest the stark differences between the neurodevelopmental effects of PFHxS and a typical goitrogen may be due, in part, to the ability of PFHxS to interact with thyroid hormone distributing proteins like transthyretin.
2025-02-12 | GSE262750 | 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: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:Thyroid hormone is know to effect growth and development. However little is know about the hormone thyroxine's effect on craniofacial growth and suture development. We used microarray as one tool to determine gene expression profile of wild type and craniosynostotic (Twist 1 +/-) suture cells after thyroxine exposure. We isolated whole RNA from Wild type C57BL6 and Twist 1 +/- suture derived calvarial cells and treated with proliferation media and with thyroxine 10^-6 mol/liter for 3 or 7 days in culture. We then used an Affymetrix array and compared expression profiles between control and experimental treatments.
2015-02-21 | E-GEOD-66149 | biostudies-arrayexpress
Project description:Thyroid hormone has a positive effect on endochondral bone growth. Few studies have looked at the interaction between thyroid hormone exposures and intramembranous bone derived cells. We used microarray as one tool to determine the gene expression profile of intramembranous (calvarial) derived murine pre-osteoblsts after thyroxine exposure. We isolated whole RNA from MC3T3-E1 cells treated with proliferation media or proliferation media with thyroxine at a dose of 10^-6 mol./liter for 3 or 7 days in culture. We then used an Affymetrix array and compared expression profiles between control and experimental treatments.
2013-05-31 | E-GEOD-47517 | biostudies-arrayexpress
Project description:Thyroid hormone is know to effect growth and development. However little is know about the hormone thyroxine's effect on craniofacial growth and suture development. We used microarray as one tool to determine gene expression profile of wild type and craniosynostotic (Twist 1 +/-) suture cells after thyroxine exposure.
2015-02-21 | GSE66149 | GEO
Project description:Analysis of Human bone mesenchymal stem cells treated separately with DMSO vehicle, 100 nM perfluorooctanesulfonat(PFOS), 100 nM perfluorooctanoic acid(PFOA), 100 nM perfluorohexanesulphonate(PFHxS) or100 nM Chlorinated polyfluoroalkyl ether sulfonate(F-53B) for 7 days. Results provide insight into the molecular mechanisms by which PFASs interfere with osteogenic differentiation potential in HBMSCs.
2019-12-31 | GSE115836 | GEO
Project description:Interventions: Case group:N/A;control group:N/A
Primary outcome(s): Organochlorine pollutant;genetic mutations
Study Design: Case-Control study
| 2661840 | ecrin-mdr-crc
Project description:Thyroid hormone has a positive effect on endochondral bone growth. Few studies have looked at the interaction between thyroid hormone exposures and intramembranous bone derived cells. We used microarray as one tool to determine the gene expression profile of intramembranous (calvarial) derived murine pre-osteoblsts after thyroxine exposure.
2013-05-31 | GSE47517 | GEO