Gene signaling pathways in liver of largemouth bass by a sub-chronic dietary exposure to EE2
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ABSTRACT:
ORGANISM(S): Micropterus salmoides
PROVIDER: GSE59224 | GEO | 2014/08/31
SECONDARY ACCESSION(S): PRJNA254757
REPOSITORIES: GEO
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Project description:The objective of this study was to investigate pathway signatures altered in the livers of female largemouth bass (LMB) and their potential links with biological responses by dietary exposure to 0.2 mg EE2/Kg (1% of their body weight) over two months using a transcriptomics approach. A high concentration of dietary 17alpha-ethinylestradiol (EE2) can activate key signaling pathways in response to oxidative damage may occur regardless of tumorigenesis and cancer. Female LMB received about 1.2g EE2/day/fish (from EE2-laced feed containing 0.2 mg EE2/Kg) for 60 days.
2014-08-31 | E-GEOD-59224 | biostudies-arrayexpress
Project description:17alpha-ethinylestradiol (EE2) is one of the most potent estrogens that have the ability to interfere with the endocrine system of fish. The objective was to investigate the effects and mechanisms of action caused by 60 days of dietary exposure to 0.2 mg EE2/kg and 0.07 mg EE2/kg feed in female largemouth bass (LMB) during the reproductive season. Microarrays and pathway analyses were performed on hepatic tissues to identify genes and biological processes altered in female LMB by EE2 exposure. The hypothesis was that the two concentrations of EE2 would produce dose-response changes in sensitive genes. Body and ovary weights were measured and blood was collected for measurement of plasma steroid hormones (17beta-estradiol (E2), testosterone (T)) and vitellogenin (VTG) using ELISA. The 0.2 mg EE2/kg feed exposure reduced the gonadosomatic index (GSI) by 75%, and plasma levels of E2 and T were reduced by over 90%. Plasma VTG was increased by approximately 100% (from 4 to 8mg/ml) by the 0.2 mg/kg treatment. T levels, from the 0.07 mg EE2/kg feed, reduced GSI by approximately 30% and circulating E2 and T by ~80% but did not affect VTG concentrations. We found 1,594 and 1,165 genes were significantly affected (p<0.05) by the 0.07 mg EE2/kg feed and 0.2 mg EE2/kg feed, respectively. Gene ontology (GO) analysis revealed that there were different biological processes regulated by the two concentrations of EE2. Pathway analysis showed that the 0.07 mg EE2/kg feed exposure caused differential regulation of genes associated with fatty acid biosynthesis and glycolysis, indicating some metabolic effects. In contrast, the 0.2 mg EE2/kg feed exposure altered transcription of genes involved in immune response and apoptosis, suggesting a toxic response at this concentration. These results suggest that the two concentrations demonstrated distinct physiological responses, with the higher concentration inducing complete endocrine disruption in LMB. These findings demonstrate the usefulness of microarrays to identify possible biomarkers and modes of toxic action to dietary exposure in LMB. Two concentrations of EE2 would produce dose-response changes in sensitive genes. Female LMB were fed 5 days per week for 60 days with floating pellets that contained 0.07 or 0.2 mg/kg of EE2.
2011-03-24 | E-GEOD-28143 | biostudies-arrayexpress
Project description:17alpha-ethinylestradiol (EE2), used for birth control in humans, is a potent estrogen that is found in wastewater at low concentrations (ng/L). EE2 has the ability to interfere with the endocrine system of fish, affecting reproduction which can result in population level effects. The objective of this study was to determine if dietary exposure to EE2 would alter gene expression patterns and key pathways in the liver and ovary and whether these could be associated with reproductive endpoints in female largemouth bass (LMB) during egg development. Female LMB received 70 ng EE2/g feed (feed administered at 1% of body weight) for 60 days. EE2 dietary exposure significantly reduced plasma vitellogenin concentrations by 70%. Hepatosomatic and gonadosomatic indices were also decreased with EE2 feeding by 38.5% and 40%, respectively. Transcriptomic profiling revealed that there were more changes in steady-state mRNA levels in the liver compared to the ovary. Genes associated with reproduction were differentially expressed such as vitellogenin in the liver and aromatase in the gonad. In addition, a set of genes related with oxidative stress (e.g., glutathione reductase and glutathione peroxidase) were identified as altered in the liver and genes associated with the immune system (e.g., complement component 1, and macrophage-inducible C-type lectin) were altered in the gonad. In a follow-up study with 0.2 ng EE2/g feed for 60 days, similar phenotypic and gene expression changes were observed that support these findings with the higher concentrations. This study provides new insights into how dietary exposure to EE2 interferes with endocrine signaling pathways in female LMB during a critical period of reproductive oogenesis.
2011-03-24 | GSE28143 | GEO
Project description:In this study, both male and female sexually regressed largemouth bass (Micropterus salmoides) (LMB) were fed a nominal concentration of 3.0 mg dieldrin/kg in feed for 60 days. A third group of male LMB was fed both 3.0 mg dieldrin/kg dieldrin and 0.7 mg E2/kg in feed. E2 was used as a model compound to elicit estrogenic effects via ER signaling.
2011-04-17 | GSE27963 | GEO
Project description:A novel custom microarray for largemouth bass (Micropterus salmoides) was designed from sequences obtained from a normalized cDNA library using the 454 Life Sciences GS-20 pyrosequencer. The GS-20 yielded in excess of 58 million bases of high-quality sequence. The sequence information was combined with 2,616 reads obtained by traditional suppressive subtractive hybridizations to derive a total of 31,391 unique sequences. Annotation and coding sequences were predicted for these transcripts where possible. 16,350 annotated transcripts were selected as target sequences for the design of the custom largemouth bass oligonucleotide microarray. The microarray was validated by examining the transcriptomic response in male largemouth bass exposed to 17 -oestradiol. Transcriptomic responses were assessed in liver and gonad, and indicated gene expression profiles typical of exposure to oestradiol. The results demonstrate the potential to rapidly create the tools necessary to assess large scale transcriptional responses in non-model species, paving the way for expanded impact of toxicogenomics in ecotoxicology. Keywords: E2 exposure, array validation
2008-08-01 | GSE10693 | GEO
Project description:Largemouth bass (Micropterus salmoides) (LMB) inhabiting Lake Apopka, Florida are exposed to high levels of organochlorine pesticides (OCPs) that exert effects through multiple modes of action. The objectives of this study were to assess the impacts of two OCPs (p,p'-Dichlorodiphenyldichloroethylene; p,p’ DDE and methoxychlor; MXC) on the reproductive axis of LMB. Female LMB were fed coated feed over 84 days of either 125 (p,p’ DDE), 10 (MXC), or 0 (control) ppm (mg/kg). In addition, due to the fact that p,p’ DDE and MXC are suspected anti-androgens, the potent anti-androgenic pharmaceutical flutamide (FLUT) was also fed to a separate group of LMB at 750 ppm. After 84 days, LMB significantly incorporated p,p’ DDE and MXC into muscle and ovary tissue. Gonadal histology and plasma sex steroids were not significantly different than controls after being fed contaminants. Microarray analysis revealed that p,p’ DDE and FLUT regulated more genes in common that either chemical compared to MXC, consistent with data suggesting that p,p’ DDE is a more potent anti-androgen than MXC. There was a significant positive correlation between 71 commonly regulated genes in all three treatments, suggesting that these transcripts may be responding to a common anti-androgenic mode of action. Cell processes affected by all three treatments included leukocyte cell adhesion, ossification, platelet function and inhibition, xenobiotic metabolism, fibrinolysis, and thermoregulation. Most striking was that all three chemicals depressed gene networks related to immune function and inflammation. This study adds to a growing number of fish transcriptomics studies investigating chemicals with an anti-androgenic MOA.
2013-08-10 | GSE47675 | GEO
Project description:Female largemouth bass were injected with 10mg/kg dieldrin and sacrificed after 7 days. Hypothalami were dissected and total RNA extracted for microarray analysis. Exposure to dieldrin induces neurotoxic effects in the vertebrate CNS and disrupts reproductive processes in teleost fish. Reproductive impairment observed in fish is likely the result of multiple mechanisms of action along the hypothalamic-pituitary-gonadal axis. To better elucidate the mode of action of dieldrin in the hypothalamus, we measured neurotransmitter levels and examined the transcriptomic response of female largemouth bass (LMB) to an acute treatment of dieldrin. Female LMB were injected with either vehicle or 10 mg/kg dieldrin and sacrificed after seven days. The neurotransmitter γ-aminobutyric acid was significantly elevated by approximately 25-30% in the hypothalamus and cerebellum but there was no change in dopamine levels in the hypothalamus, telencephalon, or cerebellum. We identified 270 transcripts (p<0.001) as being differentially regulated by dieldrin. Functional enrichment analysis identified transcription, DNA repair, ubiquitin pathway, cell communication, and phosphorylation as biological processes over-represented in the microarray analysis. Pathway analysis identified DNA damage, inflammation, regeneration, and Alzheimerâs disease as major cell processes and diseases affected by dieldrin. Using multiple bioinformatics approaches, this study demonstrates that the teleostean hypothalamus is a target for dieldrin-induced neurotoxicity and provides mechanistic evidence that dieldrin activates similar cell pathways and biological processes that are involved in the etiology of human neurological disorders. Key words: ubiquitin-proteasome pathway, mutagenicity, neurodegeneration, apoptosis, DNA damage Largemouth bass injected with single i.p. with 10 mg/kg diedrin; sacrificed 7 days later, hypothalamic tissue studied
2010-06-19 | E-GEOD-12698 | biostudies-arrayexpress
Project description:A novel custom microarray for largemouth bass (Micropterus salmoides) was designed from sequences obtained from a normalized cDNA library using the 454 Life Sciences GS-20 pyrosequencer. The GS-20 yielded in excess of 58 million bases of high-quality sequence. The sequence information was combined with 2,616 reads obtained by traditional suppressive subtractive hybridizations to derive a total of 31,391 unique sequences. Annotation and coding sequences were predicted for these transcripts where possible. 16,350 annotated transcripts were selected as target sequences for the design of the custom largemouth bass oligonucleotide microarray. The microarray was validated by examining the transcriptomic response in male largemouth bass exposed to 17 -oestradiol. Transcriptomic responses were assessed in liver and gonad, and indicated gene expression profiles typical of exposure to oestradiol. The results demonstrate the potential to rapidly create the tools necessary to assess large scale transcriptional responses in non-model species, paving the way for expanded impact of toxicogenomics in ecotoxicology. Keywords: E2 exposure, array validation This experiment tested two organs - liver and gonad from either E2-exposed or control fish, 4 fish (biological replicates) per treament (control and E2).
2010-05-25 | E-GEOD-10693 | biostudies-arrayexpress
Project description:In this study, both male and female sexually regressed largemouth bass (Micropterus salmoides) (LMB) were fed a nominal concentration of 3.0 mg dieldrin/kg in feed for 60 days. A third group of male LMB was fed both 3.0 mg dieldrin/kg dieldrin and 0.7 mg E2/kg in feed. E2 was used as a model compound to elicit estrogenic effects via ER signaling. There were four samples analyzed for 1) control males 2) control females 3) males fed 3 mg/kg dieldrin 4) females fed 3.0 mg/kg dieldrin, and 5) males fed 3.0 mg/kg dieldrin + 0.7 mg/kg E2. There was a total of 20 microarrays and sample processed.
2011-04-17 | E-GEOD-27963 | biostudies-arrayexpress
Project description:Largemouth bass (Micropterus salmoides) (LMB) inhabiting Lake Apopka, Florida are exposed to high levels of organochlorine pesticides (OCPs) that exert effects through multiple modes of action. The objectives of this study were to assess the impacts of two OCPs (p,p'-Dichlorodiphenyldichloroethylene; p,pM-bM-^@M-^Y DDE and methoxychlor; MXC) on the reproductive axis of LMB. Female LMB were fed coated feed over 84 days of either 125 (p,pM-bM-^@M-^Y DDE), 10 (MXC), or 0 (control) ppm (mg/kg). In addition, due to the fact that p,pM-bM-^@M-^Y DDE and MXC are suspected anti-androgens, the potent anti-androgenic pharmaceutical flutamide (FLUT) was also fed to a separate group of LMB at 750 ppm. After 84 days, LMB significantly incorporated p,pM-bM-^@M-^Y DDE and MXC into muscle and ovary tissue. Gonadal histology and plasma sex steroids were not significantly different than controls after being fed contaminants. Microarray analysis revealed that p,pM-bM-^@M-^Y DDE and FLUT regulated more genes in common that either chemical compared to MXC, consistent with data suggesting that p,pM-bM-^@M-^Y DDE is a more potent anti-androgen than MXC. There was a significant positive correlation between 71 commonly regulated genes in all three treatments, suggesting that these transcripts may be responding to a common anti-androgenic mode of action. Cell processes affected by all three treatments included leukocyte cell adhesion, ossification, platelet function and inhibition, xenobiotic metabolism, fibrinolysis, and thermoregulation. Most striking was that all three chemicals depressed gene networks related to immune function and inflammation. This study adds to a growing number of fish transcriptomics studies investigating chemicals with an anti-androgenic MOA. 4 biological replicates per group; control, methoxychlor, p,p DDE, and flutamide
2013-08-10 | E-GEOD-47675 | biostudies-arrayexpress