Identifying differential gene expression in TBT-treated dog whelk, Nucella lapillus
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ABSTRACT:
ORGANISM(S): Nucella lapillus
SUBMITTER: Yongxiang Fang
PROVIDER: E-MTAB-709 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Bivalves are well known sentinel organism in the detection of environmental pollutants. Bioaccumulation of these contaminants in bivalves often manifests as specific alterations of their biological processes, which are used as biomarkers for environmental pollution. Tributyltin (TBT) is one such pollutant previously used as a biocide in marine antifouling paints, it now causes a number deleterious effects in bivalves leaching out of sediments in marine ecosystems. One effect extensively documented is shell abnormalities, including shell thickening and chambering. Changes in amino acid compositions of the shell matrix are associated with these deformations suggesting that TBT mode of action influences the biological control of shell biomineralization. This environmental toxicants effect on shell biomineralization was analyzed in this investigation at a transcriptional level in order to elucidate the normal shell biomineralization process. P. maxima animals were exposed to TBT in laboratory conditions and a concentration range for chronic and acute toxicity has been established. Animals exposed to chronic concentrations were analyzed for differential gene expression using PmaxArray 1.0 microarray platform and compared against control animals. Genes indentified as differentially expressed in association with TBT exposure included up-regulation of immunity and detoxification related genes and down-regulation of several shell matrix genes. A number of novel transcripts were additionally identified. The potential actions of these genes are discussed with reference to TBT toxicity and shell biomineralization. This investigation has used a microarray to determine transcriptional effects of TBT on P. maxima and proposed the involvement of novel components in shell formation, aiding the elucidation of the process. Keywords: Expression profiling by array, stress response
2010-02-05 | GSE13980 | GEO
Project description:Bivalves are well known sentinel organism in the detection of environmental pollutants. Bioaccumulation of these contaminants in bivalves often manifests as specific alterations of their biological processes, which are used as biomarkers for environmental pollution. Tributyltin (TBT) is one such pollutant previously used as a biocide in marine antifouling paints, it now causes a number deleterious effects in bivalves leaching out of sediments in marine ecosystems. One effect extensively documented is shell abnormalities, including shell thickening and chambering. Changes in amino acid compositions of the shell matrix are associated with these deformations suggesting that TBT mode of action influences the biological control of shell biomineralization. This environmental toxicants effect on shell biomineralization was analyzed in this investigation at a transcriptional level in order to elucidate the normal shell biomineralization process. P. maxima animals were exposed to TBT in laboratory conditions and a concentration range for chronic and acute toxicity has been established. Animals exposed to chronic concentrations were analyzed for differential gene expression using PmaxArray 1.0 microarray platform and compared against control animals. Genes indentified as differentially expressed in association with TBT exposure included up-regulation of immunity and detoxification related genes and down-regulation of several shell matrix genes. A number of novel transcripts were additionally identified. The potential actions of these genes are discussed with reference to TBT toxicity and shell biomineralization. This investigation has used a microarray to determine transcriptional effects of TBT on P. maxima and proposed the involvement of novel components in shell formation, aiding the elucidation of the process. Keywords: Expression profiling by array, stress response In order to determine to differential expression profiles for transcripts relevant to TBT exposure, 9 animals treated with TBT 50 ng1-1 were compared to 9 control animals untreated on a dual channel (Cy3 and Cy5) cDNA microarrays. The RNA for the 9 control animals was pooled together for a common reference while the RNA from the 9 treated animals was separated into 3 pooled replicates, each containing RNA from 3 individual animals. Each of the pooled treatment replicates were labeled (Cy3 or Cy5) as was the controls (opposing treatment label) and hybridized to a separate microarray chip, totaling 3 chips. Each chip had duplicate spot grids printed on the left and right of the chip providing technical replication. In total 6 microarrays were challenged and analyzed comprising 3 biological replicates each with 2 technical replicates.
2010-05-14 | E-GEOD-13980 | biostudies-arrayexpress
Project description:Organotin compounds are highly persistent organic pollutants that bioaccumulate in marine biota, behaving as potent endocrine disruptors. Tributyltin (TBT) has been described as an environmental obesogen, as it contributes in mammals to lipid accumulation in a mechanism mediated by PPARγ and RXR. With the aim of studying the molecular mechanisms that elicit TBT-induced pathogenesis in fish, thicklip grey mullets Chelon labrosus were exposed to low (10 ng/L) and high (500 ng/L) TBT concentrations for 1, 7 and 21 days, and gene transcription and metabolome profiles were studied. With this purpose, the multitissue transcriptome of mullet was sequenced by 454 pyrosequencing obtaining 126 Mb of sequence information. Assembly and annotation allowed spotting 8330 gene signatures on an oligonucleotide microarray that was used to identify hepatic gene transcription profiles specific to each TBT exposure set-up. Functional pathway analysis revealed that early profiles were characterized by genes related to response to organic substances and to oxidative stress and glucose metabolic processes. After 21 days of exposure, enriched GO terms in both concentrations were related to lipid homeostasis with a significant regulation of steroid metabolic and cholesterol biosynthetic processes. Also, the androgen receptor signalling pathway was regulated while PPAR signalling appeared as the most significantly regulated KEGG pathway. Neutral lipid accumulation measured by Oil-Red-O histochemistry did not show any treatment-related effect but hepatic and plasma NMR and GC-MS metabolomic analysis revealed distinctive metabolites. Aqueous profiles were characterised by lactate, glucose and alanine while GC-MS revealed a whole set of discriminating polyunsaturated fatty acids. Thus, TBT pathogenesis involves alterations of lipid metabolism through a mechanism that could involve PPARγ-regulated processes confirming the obesogen hypothesis for TBT in fish. Thicklip grey mullets were exposed to tributyltin (TBT). 3 treatments: control, TBT low dose (10ng/L), TBT high dose (500ng/L); 3 sampling times: 1 day, 1 week, 3 weeks. 6 mullets were dissected in each sampling point and group.
2016-07-31 | E-GEOD-36811 | biostudies-arrayexpress
Project description:Tributyltin (TBT) accumulates at higher levels in the liver than in any other organ, and it acts as a hepatotoxic agent. Most of the available studies on TBT have focused on observations at the cellular level, and studies at the level of genes and proteins have been limited; therefore, the information concerning possible mechanisms of TBT-induced adverse health effects remains scarce and inconclusive. In the present study, we applied a toxicogenomic approach to investigate the effects of TBT on gene expression in the human normal liver cell line HL7702.
2016-09-01 | GSE86259 | GEO
Project description:Organotin compounds are highly persistent organic pollutants that bioaccumulate in marine biota, behaving as potent endocrine disruptors. Tributyltin (TBT) has been described as an environmental obesogen, as it contributes in mammals to lipid accumulation in a mechanism mediated by PPARγ and RXR. With the aim of studying the molecular mechanisms that elicit TBT-induced pathogenesis in fish, thicklip grey mullets Chelon labrosus were exposed to low (10 ng/L) and high (500 ng/L) TBT concentrations for 1, 7 and 21 days, and gene transcription and metabolome profiles were studied. With this purpose, the multitissue transcriptome of mullet was sequenced by 454 pyrosequencing obtaining 126 Mb of sequence information. Assembly and annotation allowed spotting 8330 gene signatures on an oligonucleotide microarray that was used to identify hepatic gene transcription profiles specific to each TBT exposure set-up. Functional pathway analysis revealed that early profiles were characterized by genes related to response to organic substances and to oxidative stress and glucose metabolic processes. After 21 days of exposure, enriched GO terms in both concentrations were related to lipid homeostasis with a significant regulation of steroid metabolic and cholesterol biosynthetic processes. Also, the androgen receptor signalling pathway was regulated while PPAR signalling appeared as the most significantly regulated KEGG pathway. Neutral lipid accumulation measured by Oil-Red-O histochemistry did not show any treatment-related effect but hepatic and plasma NMR and GC-MS metabolomic analysis revealed distinctive metabolites. Aqueous profiles were characterised by lactate, glucose and alanine while GC-MS revealed a whole set of discriminating polyunsaturated fatty acids. Thus, TBT pathogenesis involves alterations of lipid metabolism through a mechanism that could involve PPARγ-regulated processes confirming the obesogen hypothesis for TBT in fish.
2016-07-31 | GSE36811 | GEO
Project description:Obesogens such as tributyltin (TBT) are xenobiotic compounds that promote obesity, in part by distorting the normal balance of lipid metabolism. The obesogenic effects of TBT can be observed in directly exposed (F1 and F2 generations) and also subsequent generations (F3 and beyond) that were never exposed. To address the effects of TBT exposure on germ cells, we exposed pregnant transgenic OG2 mouse dams (F0), which specifically express EGFP in germline cells, to an environmentally relevant dose of TBT throughout gestation through drinking water. When fed with a high fat diet (HFD), F3 male offspring of TBT-exposed F0 dams (TBT-F3) accumulated much more body fat than did Control-F3 males. TBT-F3 males also lost more body fluid and lean compositions than did Control-F3 males. Expression of genes involved in transcriptional regulation or mesenchymal differ-entiation was upregulated in somatic cells of TBT-F1 (but not TBT-F3) E18.5 fetal testes, and promoter-associated CpG islands were hyper-methylated in TBT-F1 somatic cells. Global mRNA expression of protein-coding genes in F1 or F3 fetal testicular cells was unaffected by F0 exposure to TBT; however, expression of a subset of endogenous retroviruses was significantly affected in F1 and F3. We infer that TBT may directly target testicular somatic cells in F1 testes to irreversibly affect epigenetic suppression of endogenous retroviruses in both germline and somatic cells.
2022-03-02 | GSE191199 | GEO
Project description:Major classes of hormone mimics that have been studied include environmental estrogens and androgens, but recent studies have also demonstrated the significant impacts of natural and synthetic progesterones in the environment. The objective of this study was to evaluate the molecular and physiological impacts of progestin, anti-progestin, and mixture exposures in the Eastern Mosquitofish (G. holbrooki). By comparison of gene expression profiles and modulated biological processes in the three groups, it was determined that mifepristone acts more as a progestin than as an anti-progestin, as has also been demonstrated in other species of fish. This work contributes to the overall knowledge of the impacts of this class of chemical contaminats on aquatic organisms, which are a sentinel species for pollutants as aquatic ecosystems often become a reservoir for anthropogenic contaminants.
2014-09-01 | GSE55518 | GEO
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:Environmental obesogens are being studied for their potential role in the increasing prevalence of obesity globally. A major area of focus in this field of research has been on the mechanism by which these agents act. In this study we focused on the organotin tributyltin (TBT), a water pollutant exposed to humans through diet. The mechanism by which TBT is believed to act is by binding to the PPAR nuclear receptor which heterodimerizes with RXR to alter gene regulation. To test whether this was the dominant mechanism for TBT activity, we performed time-course studies of transcription and chromatin accessibility in mesenchymal stem cells differentiating to adipocytes. We found limited evidence for PPAR effects by TBT, but a strong response by Ras-related GTPases and evidence for the loss of TEAD transcription factor activity during differentiation. These observations combine to implicate a known property of organotins, to cause cytoskeletal depolymerization. We propose a model for TBT activity involving a primary effect of cytoskeletal damage, leading to the loss of YAP co-regulator activity and the consequent failure of TEAD repression of adipogenesis.
2024-01-01 | GSE207038 | GEO
Project description:Environmental obesogens are being studied for their potential role in the increasing prevalence of obesity globally. A major area of focus in this field of research has been on the mechanism by which these agents act. In this study we focused on the organotin tributyltin (TBT), a water pollutant exposed to humans through diet. The mechanism by which TBT is believed to act is by binding to the PPAR nuclear receptor which heterodimerizes with RXR to alter gene regulation. To test whether this was the dominant mechanism for TBT activity, we performed time-course studies of transcription and chromatin accessibility in mesenchymal stem cells differentiating to adipocytes. We found limited evidence for PPAR effects by TBT, but a strong response by Ras-related GTPases and evidence for the loss of TEAD transcription factor activity during differentiation. These observations combine to implicate a known property of organotins, to cause cytoskeletal depolymerization. We propose a model for TBT activity involving a primary effect of cytoskeletal damage, leading to the loss of YAP co-regulator activity and the consequent failure of TEAD repression of adipogenesis.
2024-01-01 | GSE207039 | GEO