Evaluation of hepatic gene expression profiles during androgen exposure in female mosquitofish
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ABSTRACT:
ORGANISM(S): Gambusia holbrooki
PROVIDER: GSE45261 | GEO | 2013/04/01
SECONDARY ACCESSION(S): PRJNA193337
REPOSITORIES: GEO
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Project description:The Eastern Mosquitofish (Gambusia holbrooki) is a non-model species with the potential for development of biomarkers of endocrine disrutpting chemical (EDC) exposure due to its androgen-driven secondary sexual characteristics. While G. holbrooki have been utilized in the field as bioindicator organisms EDC exposure in areas impacted by pulp and paper mills, the lack of molecular tools and general understanding of how G. holbrooki are impacted by androgen exposure hinder the use of this organism as a widespread tool for the evaluation of these chemicals in the environment. While traditional gene-by-gene approaches have provided a list of genes that may be appropriate for developing into biomarkers of androgen exposure, a more inclusive method could provide more rapid and expansive determination of genes that can be developed into biomarkers of androgen exposure. The objective of this study is toutilize a mosquitofish microarray to determine potential biomarkers of chronic androgen exposure. The specific aim was to determine genes that may be developed into biomarkers of chronic androgen exposure in hepatic tissues using 17M-NM-2-trenbolone (TB) exposed adult female G. holbrooki by microarray analysis. Liver tissues from a 14-day exposure of female G. holbrooki to 1 M-BM-5g/L of the potent androgen receptor agonist 17M-NM-2-trenbolone (17M-NM-2-hydroxyestra-4,9,11-trien-3-one; abbreviated as TB) [Brockmeier 2013] were used as the first sample for microarray analysis using the custom G. holbrooki microarray to determine genes that were significantly up or down-regulated during a chronic androgen agonist exposure. RNA was isolated from the livers as previously described using TRIzol (Invitrogen, Grand Island, USA), hydrated using RNAsecure (Ambion, Grand Island, USA), and DNase treated using the Turbo DNA-free kit (Ambion, Grand Island, USA). Four oocyte-development stage-matched RNA samples per treatment were evaluated for RNA integrity using the 2100 BioAnalyzer (Agilent, Santa Clara, USA). The range of RIN values was 8.3-8.9.
2013-04-01 | E-GEOD-45261 | biostudies-arrayexpress
Project description:Trenbolone and flutamide are prototypical model compounds for respectively androgen and anti-androgen modes of action. Trenbolone is an anabolic steroid used in cattle industry to increase weight gain and feed efficiency, and flutamide is a pharmaceutical used to treat prostate cancer. Androgens exert profound effects on the organization, development, and function of the male reproductive system through activation of androgen receptors (ARs). Flutamide, as an antiandrogen, was expected to temper the effects of trenbolone on androgen receptor (AR)-mediated gene expression. Female fathead minnows (Pimephales promelas) were exposed via the water to 0.05, 0.5 or 5 µg 17β-trenbolone/L; 50, 150 or 500 µg flutamide/L; or to a mixture of 0.5 μg/L trenbolone and 500 μg/L flutamide. After a 48 hr constant exposure gene expression in gonads was analyzed using a fathead minnow-specific 22,000-gene microarray. Trenbolone significantly changed the expression (P < 0.05) of roughly 750 different genes, while flutamide changed the expression of 1420 genes. Most of the genes that were regulated were distinct for the two chemicals. However, 70 genes were reciprocally regulated by the two treatments. Myelocytomatosis viral oncogene homolog (Myc), Yin Yang 1 (YY1) and interferon regulator factor 1 (IRF1) were among the important transcription factors reciprocally regulated by trenbolone and flutamide, suggesting they may be specifically regulated by the AR. These regulatory molecules, in conjunction with other reciprocally regulated transcription factors, may function as early molecular switches to control phenotypic changes in gonad tissue architecture and function. Fathead minnows exposed for 48h to 0.5 ug trenbolone, 500 ug flutamide, or a mixture of both.
2008-12-23 | E-GEOD-14100 | biostudies-arrayexpress
Project description:Trenbolone and flutamide are prototypical model compounds for respectively androgen and anti-androgen modes of action. Trenbolone is an anabolic steroid used in cattle industry to increase weight gain and feed efficiency, and flutamide is a pharmaceutical used to treat prostate cancer. Androgens exert profound effects on the organization, development, and function of the male reproductive system through activation of androgen receptors (ARs). Flutamide, as an antiandrogen, was expected to temper the effects of trenbolone on androgen receptor (AR)-mediated gene expression. Female fathead minnows (Pimephales promelas) were exposed via the water to 0.05, 0.5 or 5 µg 17β-trenbolone/L; 50, 150 or 500 µg flutamide/L; or to a mixture of 0.5 μg/L trenbolone and 500 μg/L flutamide. After a 48 hr constant exposure gene expression in gonads was analyzed using a fathead minnow-specific 22,000-gene microarray. Trenbolone significantly changed the expression (P < 0.05) of roughly 750 different genes, while flutamide changed the expression of 1420 genes. Most of the genes that were regulated were distinct for the two chemicals. However, 70 genes were reciprocally regulated by the two treatments. Myelocytomatosis viral oncogene homolog (Myc), Yin Yang 1 (YY1) and interferon regulator factor 1 (IRF1) were among the important transcription factors reciprocally regulated by trenbolone and flutamide, suggesting they may be specifically regulated by the AR. These regulatory molecules, in conjunction with other reciprocally regulated transcription factors, may function as early molecular switches to control phenotypic changes in gonad tissue architecture and function.
2008-12-23 | GSE14100 | GEO
Project description:Endocrine active substances present significant risks to both human health and the environment, particularly by disrupting essential endocrine-regulated functions like organism development and reproductive capacity. Regulatory frameworks mandate animal testing for chemical risk assessment, placing specific emphasis on suspected endocrine disruptors. For example, aquatic vertebrate chronic toxicity testing is mandatory at a chemical tonnage of 100 t/y using the Fish Early Life Stage (FELS, OECD TG 210) test. However, suspected endocrine disruptors are subjected to testing from a lower tonnage threshold of 10 t/y. Currently, the assessment of endocrine effects adheres to an OECD Conceptual Framework (CF) that employs a tiered approach. This entails evaluating existing data for potential endocrine effects (Level 1), conducting mechanism of action-specific in vitro studies (Level 2), and undertaking in vivo mechanistic screening studies (Level 3). If screening studies indicate potential endocrine disruption, further investigation is conducted using a Fish Sexual Development Test (FSDT, OECD TG 234) to clarify (anti)estrogenic, (anti)androgenic, and steroidal effects (EAS effects) in fish. Nevertheless, this testing process is resource-intensive, time-consuming, and involves extensive animal use. Therefore, this study aims to identify the androgenic activity of trenbolone using the zebrafish embryo model. Trenbolone, a synthetic anabolic steroid, primarily exerts its effects by binding to androgen receptors. The data collected will be compared with those obtained from androstenedione exposure to zebrafish embryos.
2024-08-31 | E-MTAB-14032 | biostudies-arrayexpress
Project description:Masculinized female Eastern Mosquitofish (Gambusia holbrooki) have resided downstream of paper mills in Florida since the 1980's. The potential impacts of this effluent on the mosquitofish endocrine system are unknown. The objective of this study was to evaluate gene expression patterns of endocrine system genes and global gene expression patterns in female G. holbrooki from a paper mill-impacted site. Masculinized female G. holbrooki were collected from a paper mill-impacted site (Fenholloway River) and from a reference site (Econfina River) and microarray analysis in livers was conducted. Hepatic microarray analysis revealed an increase in the expression of metabolic genes at the Fenholloway, with similarities in individual genes and biological processes compared to G. holbrooki exposed to androgens. These data indicate G. holbrooki from the Fenholloway may be impacted by a mixture of endocrine-active chemicals, including androgens.
2013-11-01 | GSE49238 | GEO
Project description:We investigated the genomic transcriptional response of female fathead minnows (Pimephales promelas) to an acute (4 day) exposure to 0.1 or 1.0 µg/L of, 17β-trenbolone (TB), the active metabolite of an anabolic androgenic steroid used as a growth promoter in cattle and a contaminant of concern in aquatic systems. Our objectives were to investigate the gene expression profile induced by TB, define biomarkers of exposure to TB, and increase our understanding of the mechanisms of adverse effects of TB on fish reproduction. In female gonad tissue, microarray analysis using a 22K oligonucleotide microarray (EcoArray Inc., Gainesville, FL) showed 99 significantly upregulated genes and 741 significantly downregulated genes in response to 1 µg TB/L. In particular, hydroxysteroid (17β) dehydrogenase 12a (hsd17b12a), zona pellucida glycoprotein 2.2 (zp2.2), and protein inhibitor of activated STAT, 2 (pias2) were all downregulated in gonad. 4 control samples compared to 4 exposed samples, ovary.
2010-05-14 | E-GEOD-12904 | biostudies-arrayexpress
Project description:AR+ PCa cell lines show conserved activation of canonical IL-1 intracellular signaling cascades, including repression of androgen receptor mRNA levels, in response to acute IL-1 treatment and show conserved loss of sensitivity to prolonged (chronic) IL-1 intracelluar signaling, including the restoration of the androgen receptor. Thus, chronic IL-1 exposure selects for cells that have a growth advantage against cytotoxic/static inflammation, including restoration of constitutive AR expression.
2021-11-18 | GSE181229 | GEO
Project description:We investigated the genomic transcriptional response of female fathead minnows (Pimephales promelas) to an acute (4 day) exposure to 0.1 or 1.0 µg/L of, 17β-trenbolone (TB), the active metabolite of an anabolic androgenic steroid used as a growth promoter in cattle and a contaminant of concern in aquatic systems. Our objectives were to investigate the gene expression profile induced by TB, define biomarkers of exposure to TB, and increase our understanding of the mechanisms of adverse effects of TB on fish reproduction. In female gonad tissue, microarray analysis using a 22K oligonucleotide microarray (EcoArray Inc., Gainesville, FL) showed 99 significantly upregulated genes and 741 significantly downregulated genes in response to 1 µg TB/L. In particular, hydroxysteroid (17β) dehydrogenase 12a (hsd17b12a), zona pellucida glycoprotein 2.2 (zp2.2), and protein inhibitor of activated STAT, 2 (pias2) were all downregulated in gonad.
2009-01-01 | GSE12904 | GEO
Project description:We show that exposure of artificial human skin tissue to intense, picosecond-duration THz pulses affects expression levels of numerous genes associated with non-melanoma skin cancers, psoriasis and atopic dermatitis. Genes affected by intense THz pulses include nearly half of the epidermal differentiation complex (EDC) members. EDC genes, which are mapped to the chromosomal human region 1q21, encode for proteins that partake in epidermal differentiation and are often overexpressed in conditions such as psoriasis and skin cancer. In nearly all the genes differentially expressed by exposure to intense THz pulses, the induced changes in transcription levels are opposite to disease-related changes.
2013-07-09 | GSE48586 | GEO
Project description:Endocrine disrupting chemicals (EDCs) such as bisphenol S (BPS) are xenobiotic compounds that can disrupt endocrine signaling following exposure due to steric similarities to endogenous hormones within the body. EDCs have been shown to induce disruptions in normal epigenetic programming (epimutations) that accompany dysregulation of normal gene expression patterns that appear to predispose disease states. Most interestingly, the prevalence of epimutations following exposure to many different EDCs often persists over multiple subsequent generations, even with no further exposure to the causative EDC. Many previous studies have described both the direct and prolonged effects of EDC exposure in animal models, but many questions remain about molecular mechanisms by which EDCs initially induce epimutations or contribute to the propagation of EDC-induced epimutations either within the exposed generation or to subsequent generations. Additional questions remain regarding the extent to which there may be differences in cell type-specific susceptibilities to various EDCs, and whether this susceptibility is correlative with expression of relevant hormone receptors and/or the location of relevant hormone response elements (HREs) in the genome. To address these questions, we exposed cultured mouse pluripotent (induced pluripotent stem [iPS]), somatic (Sertoli and granulosa), and germ (primordial germ cell like [PGCLCs]) cells to BPS and measured changes in DNA methylation levels at the epigenomic level and gene expression at the transcriptomic level. We found that there was indeed a difference in cell type-specific susceptibility to EDC-induced epimutagenesis and that this susceptibility correlated with differential expression of relevant hormone receptors and, in many cases, tended to generate epimutations near relevant HREs within the genome. Additionally, however, we also found that BPS can induce epimutations in a cell type that does not express relevant receptors and in genomic regions that do not contain relevant HREs, suggesting that both canonical and non-canonical signaling mechanisms can be disrupted by BPS exposure. Most interestingly, we found that when iPS cells were exposed to BPS and then induced to differentiate into PGCLCs, the prevalence of epimutations and differentially expressed genes (DEGs) initially induced in the iPSCs was largely retained in the resulting PGCLCs, however, >90% of the specific epimutations and DEGs were not conserved but were rather replaced by novel epimutations and DEGs following the iPSC to PGCLC transition. These results suggest a unique mechanism by which an EDC-induced epimutated state may be propagated transgenerationally following a single exposure to the causative EDC.
2024-01-31 | GSE252520 | GEO