Gene expression-based, individualized outcome prediction for exposure of rat ovarian tissue
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE108499 | GEO | 2019/12/25
REPOSITORIES: GEO
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Project description:Transcriptomic profiling of Daphnia magna samples exposed to tributyltin (TBT), pyriproxyfen (PP) and bisphenol A (BPA) at 8 and 24 hours. The analysis of lipid disruptive effects in invertebrates is limited by our poor knowledge of their lipidomes and of the associated metabolic pathways. Here we analyzed the subsequent transcriptome changes, using tributyltin (TBT), pyriproxyfen (PP) and bisphenol A (BPA). Changes in the whole transcriptome were assessed after 8 and 24 h of exposure, the period showing the greatest variation in storage lipid accumulation. The three compounds affected similarly to a total of 1388 genes (965 overexpressed and 423 underexpressed transcripts), but only after 24h of exposure. In addition,225 transcripts became up-regulated only in samples exposed to tributyltin for both 8h and 24 h. Using functional annotation from D. melanogaster, we determined that upregulated genes were enriched in members of KEGG modules implicated in fatty acid, phosphoinositol, glycerophospholipid, and glycerolipid metabolic pathways, as well as in genes related to membrane constituents , and to chitin and cuticle metabolic pathways. Conversely, down-regulated genes appeared mainly related with to visual perception, and to oocyte development signalling pathways. Many tributyltin specifically upregulated genes were related to neuro-active ligand receptor interaction signalling pathway. These changes are consistent with the previous observation that exposure of D. magna to the tested compounds increases lipid accumulation and reduces egg quality.
2019-09-01 | GSE119329 | GEO
Project description:Purpose: To profile the circular RNAs (circRNAs), microRNAs (miRNA), and mRNAs expression in BPA exposed GC-2 cells and normally cultured cells. Methods: For circRNA sequencing, total RNA was depleted of rRNA and then linear RNAs by RNase R digestion. cDNA library was constructed according to the Illumina TruSeq library preparation protocol. The Hiseq3000 sequencing platform (Illumina, San Diego, CA, USA) was used for circRNA sequencing. The sequence depth is 10G. Sequences were mapped using STAR software against GRCm38/mm10 mouse reference genome in UCSC Known Genes databases. CIRCexplorer software was applied to analyze the back-spliced junction for circular RNA prediction. Small RNA sequencing was performed on Hiseq2500in 10M sequence depth after regular small RNA library preparation. After adaptor trimming by FASTXToolkit (0.0.14), reads were aligned to the mouse genome (GRCm38/mm10) with Bowtie software (version 1.1.0). miRBase v21 and miRDeep2 were used to annotate or forecast new miRNAs respectively.Hiseq2500 platform was used to sequence mRNA in 6G depth after strand-specific library construction with TruSeq RNA LTPrep Kit (Illumina, San Diego, CA, USA). Clean reads were aligned to reference genome (mouse GRCm38/mm10) with STAR software. And StringTie and Cuffcompare were used for transcription assembly and novel transcription prediction. Results: A total of 4706 and 6486 circRNAs were identified in normally grow GC-2 cells and BPA treated cells respectively, with most not reported in circBase. According to the screening criterion of two folds, 4821 circRNAs were up-regulated and 2855 circRNAs were down-regulated compared to control group. The amounts and kinds of circRNAs were generally enhanced under BPA stress. Similar to circRNAs, miRNA sequencing also showed that more miRNAs were up-regulated than down-regulated under BPA stress (689 up and 98 down by ≥2 folds). In mRNA sequencing, 2978 genes were up-regulated and 2381 were down-regulated by at least 2 folds after BPA treatment. Conclusions: Our study was the first to delineate the full landscape of circRNAs/miRNAs/mRNAs in BPA induced reproductive toxicity. Many functional circRNAs and miRNAs were found to be activated under BPA exposure. They hold great promise to be developed as sensitive biomarkers for BPA exposure and targets for BPA toxity blocking.
2019-01-24 | GSE120921 | GEO
Project description:Gene expression profiles of granulosa cells from rat ovarian follicles by Affymetrix rat whole genome array showed that twelve genes were up-regulated, while one gene down-regulated more than 1.5 folds in the normal developmental competence group compared with those in the poor developmental competence group. Gene ontology classification showed that the up-regulated genes included lysyl oxidase and nerve growth factor receptor associated protein 1, which are important in the regulation of protein-lysine 6-oxidase activity, and in apoptosis induction, respectively. The down-regulated genes included glycoprotein-4-beta galactosyltransferase 2, which is involved in the regulation of extracellular matrix organization and biogenesis. Keywords: Dose response
2007-05-11 | GSE7697 | GEO
Project description:Background: Exposure to the endocrine-disrupting chemical bisphenol A (BPA) is correlated with obesity and promotes adipogenesis of human preadipocytes into mature adipocytes. However, the mechanism of action of BPA-induced human adipogenesis in vitro remains to be fully characterized. Methods: In this study, potential mechanisms of BPA-induced adipogenesis in primary human preadipocytes were evaluated using gene expression microarray analysis. Preadipocytes from donors with normal body mass indexes were differentiated in the presence of 50 µM BPA or 1 µM dexamethasone (DEX) for 48 hours. Results: Microarray analysis revealed 235 up-regulated and 138 down-regulated genes following BPA treatment, including sterol regulatory element binding factor 1 (SREBF1), a key transcription factor known to regulate many components of lipid metabolism and adipogenesis. For DEX treated preadipocytes, 1136 genes were up-regulated, including the adipogenic marker lipoprotein lipase, while 1031 genes were down-regulated. Ingenuity Pathway Analysis was used to identify functional annotations of the gene expression changes associated with response to BPA and DEX treatments. BPA exposure was associated with expression changes in the genes involved in the accumulation of triacylglycerol while DEX was linked to metabolism of triacylglycerol and cleavage of fatty acids. The analysis also revealed enrichment of genes in pathways known to be associated with BPA exposure including thyroid-receptor/retinoic X receptor (TR/RXR) activation, mammalian target of rapamycin (mTOR) signaling and cholesterol biosynthesis, whereas DEX treatment was linked to cholesterol biosynthesis and ethanol degradation. Interestingly, alterations in the mTOR pathway in response to BPA did not occur in DEX-treated preadipocytes. Conclusions: Our data suggest that potential mechanisms of action of BPA-induced adipogenesis involve SREBF1, the TR/RXR and the mTOR pathways.
2014-04-15 | GSE56085 | GEO
Project description:Background: Exposure to the endocrine-disrupting chemical bisphenol A (BPA) is correlated with obesity and promotes adipogenesis of human preadipocytes into mature adipocytes. However, the mechanism of action of BPA-induced human adipogenesis in vitro remains to be fully characterized. Methods: In this study, potential mechanisms of BPA-induced adipogenesis in primary human preadipocytes were evaluated using gene expression microarray analysis. Preadipocytes from donors with normal body mass indexes were differentiated in the presence of 50 M-BM-5M BPA or 1 M-BM-5M dexamethasone (DEX) for 48 hours. Results: Microarray analysis revealed 235 up-regulated and 138 down-regulated genes following BPA treatment, including sterol regulatory element binding factor 1 (SREBF1), a key transcription factor known to regulate many components of lipid metabolism and adipogenesis. For DEX treated preadipocytes, 1136 genes were up-regulated, including the adipogenic marker lipoprotein lipase, while 1031 genes were down-regulated. Ingenuity Pathway Analysis was used to identify functional annotations of the gene expression changes associated with response to BPA and DEX treatments. BPA exposure was associated with expression changes in the genes involved in the accumulation of triacylglycerol while DEX was linked to metabolism of triacylglycerol and cleavage of fatty acids. The analysis also revealed enrichment of genes in pathways known to be associated with BPA exposure including thyroid-receptor/retinoic X receptor (TR/RXR) activation, mammalian target of rapamycin (mTOR) signaling and cholesterol biosynthesis, whereas DEX treatment was linked to cholesterol biosynthesis and ethanol degradation. Interestingly, alterations in the mTOR pathway in response to BPA did not occur in DEX-treated preadipocytes. Conclusions: Our data suggest that potential mechanisms of action of BPA-induced adipogenesis involve SREBF1, the TR/RXR and the mTOR pathways. The study used 40 samples in total which included 5 replicates (cells from 5 unique donors) of 8 different treatments. The 8 treatments were as follows: 1) untreated (negative) control for 48 hours, 2) 25 uM BPA treated for 48 hours, 3) 50 uM BPA treated for 48 hours, 4) untreated (negative) control + insulin for 48 hours, 5) 25 uM BPA + insulin treated for 48 hours, 6) 50 uM BPA + insulin treated for 48 hours, 7) 1uM Dexamethasone + insulin treated for 48 hours, 8) 1uM Dexamethasone + insulin treated for 96 hours.
2014-04-15 | E-GEOD-56085 | biostudies-arrayexpress
Project description:Genes up and down regulated in LNCaP cells overexpressing MED1
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Project description:We reported that, in C57BL/6Slac mice, prenatally exposure to low-dose BPA induces up-regulation of genes associated with neuronal function and down-regulation of genes related to mitochondrial oxidative phosphorylation. Three-dimensional chromatin organization of these differential expressed genes revealed that up-regulated genes are primarily under control of remote enhancers, while down-regulated genes appear to be regulated by chromatin interactions among relative adjacent genes. Further examination of genome-wide repressive epigenetic modifications, specifically DNA methylation, H3K27me3, and H3K9me3 revealed that transcription of down-regulated genes might be repressed directly by enhanced DNA methylation and H3K27me3 modifications at promoter regions and indirectly by increased DNA methylation at their corresponding interaction regions, while up-regulated genes might be regulated by loss of H3K9me3 occupancy on distal regulatory regions.
2024-05-29 | GSE249015 | GEO
Project description:We reported that, in C57BL/6Slac mice, prenatally exposure to low-dose BPA induces up-regulation of genes associated with neuronal function and down-regulation of genes related to mitochondrial oxidative phosphorylation. Three-dimensional chromatin organization of these differential expressed genes revealed that up-regulated genes are primarily under control of remote enhancers, while down-regulated genes appear to be regulated by chromatin interactions among relative adjacent genes. Further examination of genome-wide repressive epigenetic modifications, specifically DNA methylation, H3K27me3, and H3K9me3 revealed that transcription of down-regulated genes might be repressed directly by enhanced DNA methylation and H3K27me3 modifications at promoter regions and indirectly by increased DNA methylation at their corresponding interaction regions, while up-regulated genes might be regulated by loss of H3K9me3 occupancy on distal regulatory regions.
2024-05-29 | GSE249014 | GEO
Project description:We reported that, in C57BL/6Slac mice, prenatally exposure to low-dose BPA induces up-regulation of genes associated with neuronal function and down-regulation of genes related to mitochondrial oxidative phosphorylation. Three-dimensional chromatin organization of these differential expressed genes revealed that up-regulated genes are primarily under control of remote enhancers, while down-regulated genes appear to be regulated by chromatin interactions among relative adjacent genes. Further examination of genome-wide repressive epigenetic modifications, specifically DNA methylation, H3K27me3, and H3K9me3 revealed that transcription of down-regulated genes might be repressed directly by enhanced DNA methylation and H3K27me3 modifications at promoter regions and indirectly by increased DNA methylation at their corresponding interaction regions, while up-regulated genes might be regulated by loss of H3K9me3 occupancy on distal regulatory regions.
2024-05-29 | GSE249013 | GEO
Project description:We reported that, in C57BL/6Slac mice, prenatally exposure to low-dose BPA induces up-regulation of genes associated with neuronal function and down-regulation of genes related to mitochondrial oxidative phosphorylation. Three-dimensional chromatin organization of these differential expressed genes revealed that up-regulated genes are primarily under control of remote enhancers, while down-regulated genes appear to be regulated by chromatin interactions among relative adjacent genes. Further examination of genome-wide repressive epigenetic modifications, specifically DNA methylation, H3K27me3, and H3K9me3 revealed that transcription of down-regulated genes might be repressed directly by enhanced DNA methylation and H3K27me3 modifications at promoter regions and indirectly by increased DNA methylation at their corresponding interaction regions, while up-regulated genes might be regulated by loss of H3K9me3 occupancy on distal regulatory regions.
2024-05-29 | GSE249012 | GEO