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Blood transcriptome responses to PFOA and GenX treatment in the marsupial biomedical model Monodelphis domestica

ABSTRACT: Blood transcriptome responses to PFOA and GenX treatment in the marsupial biomedical model Monodelphis domestica

PROVIDER: PRJNA858827 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR20210900_1.fastq.gz	Fastqsanger.gz
	SRR20210900_2.fastq.gz	Fastqsanger.gz
	SRR20210901_1.fastq.gz	Fastqsanger.gz
	SRR20210901_2.fastq.gz	Fastqsanger.gz
	SRR20210902_1.fastq.gz	Fastqsanger.gz

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Blood transcriptome responses to PFOA and GenX treatment in the marsupial biomedical model Monodelphis domestica

Project description:The objective of our study is to investigate the effect of PFOA and GenX on the gene expression levels in Monodelphis domestica whole blood cultures by RNA-seq and identify the major susceptible genes. We identified 578 differentially expressed genes (DEGs) in the PFOA treatment group and 148 DEGs in the GenX treatment group. 10 genes were selected for qRT-PCR validation and were confirmed to be DEGs. Pathway enrichment analysis revealed that several developmental processes were altered after PFOA exposure and showed an up-regulated pattern. And down-regulated DEGs after PFOA exposure were enriched for metabolic process and immune system process. GenX exposure is associated with up-regulated fatty acid transport pathways and inflammatory process. Our study is the first one to investigate the effects of PFASs on marsupial animals, providing supportive evidence of the similar transcriptomic alterations caused by PFOA and a fluorinated alternative GenX, which can work as a complement of the previous studies of PFASs effects on rodent or human.

2022-10-15 | GSE208237 | GEO

Blood transcriptome responses to PFOA and GenX treatment in the marsupial biomedical model <i>Monodelphis domestica</i>.

Project description:Introduction: Perfluoroalkyl and poly-fluoroalkyl substances (PFASs) are widely used in industrial and consumer products. Due to their environmental persistence and bioaccumulation, PFASs can be found in the blood of humans and wild animals all over the world. Various fluorinated alternatives such as GenX have been developed to replace the long-chain PFASs, but there is limited information about their potential toxicity. Methods:The current study developed blood culture protocols to assess the response to toxic compounds in the marsupial, Monodelphis domestica. After whole-blood culture conditions were tested and optimized, changes in gene expression in response to PFOA and GenX treatment were assessed. Results: More than 10,000 genes were expressed in the blood transcriptomes with and without treatment. Both PFOA and GenX treatment led to significant changes in the whole blood culture transcriptomes. A total of 578 and 148 differentially expressed genes (DEGs) were detected in the PFOA and GenX treatment groups, 32 of which overlapped. Pathway enrichment analysis revealed that DEGs involved in developmental processes were upregulated after PFOA exposure, while those enriched for metabolic and immune system processes were downregulated. GenX exposure upregulated genes associated with fatty acid transport pathways and inflammatory processes, which is consistent with previous studies using rodent models. Discussion: To our knowledge, this study is the first to investigate the effect of PFASs in a marsupial model. The findings provide supportive evidence for significant transcriptomic alterations, suggesting that this mammalian model may provide a mechanism for exploring the potential toxicity of PFOA and GenX.

| S-EPMC9974665 | biostudies-literature

Transcriptional profilling of liver from C57BL/6 wildtype and PPARα-knockout mice treated with PFOA and GenX after 20 weeks of high-fat diet

Project description:Perfluoroalkyl substances (PFAS) are man-made chemicals with suspected endocrine-disrupting properties. Exposure to perfluorooctanoic acid (PFOA) has been linked to disturbed metabolism via the liver, although the exact mechanism is not clear. Moreover, information on the metabolic effects of the new PFAS alternative GenX is limited. We tested whether low-dose exposure to PFOA and GenX induces metabolic disturbances, including NAFLD, dyslipidemia, and glucose tolerance in mice and studied the involvement of PPARα. To this end, male C57BL/6J wildtype and PPARα−/− mice were given 0.05 or 0.3 mg/kg bw/day PFOA, or 0.3 mg/kg bw/day GenX next to a high-fat diet for 20 weeks. RNA sequencing was performed on liver, next to thorough assesment of metabolic parameters. RNA sequencing revealed that whereas the effects of GenX are entirely dependent on PPARα, effects of PFOA are mostly dependent on PPARα. In the absence of PPARα, the involvement of PXR/CAR becomes more prominent. Exposure to high-dose PFOA in mice decreased body weights and increased liver weights in wildtype and PPARα−/− mice. High-dose but not low-dose PFOA reduced plasma triglycerides and cholesterol, which for triglycerides, showed PPARα dependency. PFOA and GenX increased hepatic triglycerides in a PPARα-dependent manner. Overall, we show that long-term and low-dose exposure to PFOA and GenX disrupts lipid metabolism in mice. Whereas the effects of PFOA are mediated by multiple nuclear receptors, effects of GenX are entirely mediated by PPARα. Our data underscore the potential of PFAS to disrupt metabolism by altering signaling pathways in the liver.

2022-09-02 | GSE212294 | GEO

Gene expression signature of three different fat depots of Monodelphis domestica of different ages

Project description:Monodelphis domestica develops ex utero. Here, we have investigated the changes in the transcriptomics of adipose tissue during juvenile development to get further insights into the reprograming in marsupial mammals.

2024-02-01 | GSE224318 | 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).

2022-11-29 | GSE199233 | GEO

Monodelphis domestica

Project description:Gene expression profile of postnatal lung development in the marsupial opossum (Monodelphis domestica)

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Ab initio identification of a marsupial-specific imprinted gene via genome-wide histone state profiling in opossum fibroblasts

Project description:We generated genome-wide histone maps of four histone modifications, H3K4me3, H3K9Ac, H3K9me3, and H3K27me3, by ChIP-seq in male fibroblasts isolated from a model marsupial, Monodelphis domestica. We assayed the correlation and association of these histone modifications with each other, certain genomic elements such as CpG islands and predicted promoters, and the transcriptional states of the genes they mark. Generally, we found that promoters of actively transcribed genes are associated with H3K4me3 and H3K9Ac and lack H3K9me3 and H3K27me3. We also show that transcriptionally opposing, mutually exclusive histone modifications mark monoallelically expressed and imprinted genes in our samples.

2014-11-07 | GSE47723 | GEO

Monodelphis domestica induced pluripotent stem cells reveal metatherian pluripotency architecture

Project description:Marsupials have been a powerful comparative model to understand mammalian biology. However, because of the unique characteristics of their embryology, marsupial pluripotency architecture remains to be fully understood, and nobody has succeeded in developing embryonic stem cells (ESCs) from any marsupial species. We have developed an integration-free induced pluripotent stem cell (iPSC) reprogramming method and established validated iPSC lines from two fully inbred strains of the gray short-tailed opossum (Monodelphis domestica). A comprehensive characterization of the M. domestica skin fibroblasts and their reprogrammed iPSCs was performed by genome-wide mRNA sequencing. The established monoiPSCs showed a significant (6,181 DE genes) but highly uniform (between clone r2 at 95% CI = 0.973 ± 0.007) resetting of the cellular transcriptome during reprogramming and were highly similar to eutherian ESCs and iPSCs in their overall transcriptomic and functional profiles. However, monoiPSCs showed unique regulatory architecture of the core pluripotency transcription factors and were more like epiblasts. Our results suggest POU5F1 and the splice variant specific expression of POU5F3 synergistically regulate the opossum pluripotency gene network. It is plausible that POU5F1, POU5F3 splice variant XM_016427856.1, and SOX2 form a self-regulatory network. NANOG expression, however, was specific to monoiPSCs and epiblasts, and displayed a distinct expression profile in embryonic cells. Furthermore, POU5F1 was highly expressed in trophectoderm cells, whereas all other pluripotency transcription factors were significantly downregulated, suggesting that the regulatory architecture of core pluripotency genes of marsupials may be distinct from that of eutherians.

2022-11-02 | GSE206122 | GEO

Project Genx-CDI

Project description:Project Genx-CDI_Raw sequence reads

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AD PFOA

Project description:AD PFOA Raw sequence reads

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