Sexually dimorphic transcriptomic responses in the largemouth bass to the neuroactive pesticide dieldrin
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ABSTRACT:
ORGANISM(S): Micropterus salmoides
SUBMITTER: Christopher Martyniuk
PROVIDER: E-GEOD-27963 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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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: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: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: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 Alzheimer’s 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
2008-09-08 | GSE12698 | GEO
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:Female Atlantic cod (Gadus morhua)were devided in to five groups and oraly exposed to alkylphenols and produced water for 20 weeks. Differentially expressed genes were studied in liver samples using the CodStress array. The five groups were fed with feed-paste containing two different doses of the AP mixture (Low AP and High AP), PW, 17?-estradiol (E2) and toxicant-free paste (control group) respectively. The body burden for each compound corresponded to 20 ?g/kg of total AP in Low AP group, 4000 ?g/kg ?g/kg of total AP in High AP group, 100 ?g E2/kg in the E2 group 500 mg PW/kg in the PW group.
2009-03-25 | E-TABM-676 | 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,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: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
Project description:Aim: We investigated the role of GR in Auditory Fear Conditioning memory consolidation by application of a pharmacological filter using selective glucocorticoid receptor modulators. Methods: Adult male mice were exposed to Auditory Fear Conditioning training and subsequently injected with 3.0 mg/kg corticosterone, 20 mg/kg CORT108297, 80 mg/kg CORT118335, 40 mg/kg RU486 or vehicle. Dorsal hippocampi were dissected 3 hours after injection and snap-frozen. Total RNA was isolated and send for 100bp paired-end sequencing by BGI.
2023-05-01 | GSE202236 | GEO
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.
2014-08-31 | GSE59224 | GEO