MRNA-seq of gonads from adult zebrafish treated with aromatase inhibitor and control
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PROVIDER: PRJNA508758 | ENA |
REPOSITORIES: ENA
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Project description:To explore the transcriptional effects of aromatase inhibitors on sex differentiation of zebrafish, we exposed 3-month-old zebrafish (AB strain) to the third generation aromatase inhibitor Exemestane (CAS: 107868-30-4) and characterized transcript abundance among testes and ovaries after 32 days of drug exposure. After the drug treatment, we dissected zebrafish gonads, isolated polyA+ RNA and performed high-throughput RNA-Seq analysis.
2019-12-07 | GSE123439 | GEO
Project description:To identify key genes in the early sex development of zebrafish, we generated zebrafish (AB strain) feminized by sex hormone 17β-estradiol (E2, CAS: 50-28-2, 100 ng/L) and masculinized by aromatase inhibitor exemestane (EM, CAS: 107868-30-4, 10 μg/L), and detected their transcriptomes by RNA-seq.
2022-05-11 | GSE126039 | GEO
Project description:Cytochrome P450 aromatase is an essential enzyme for vertebrates. It is responsible for the conversion of androgens to estrogens in the brain and gonadal tissues. Aromatase converts testosterone into estradiol and therefore participates in the regulation of many processes which are controlled by estrogens such as development and fertility. Teleosts have been characterized as having exceptionally high levels of brain estrogen biosynthesis when compared to the brains of the other vertebrates. Little is known about the effects of estrogens on brain function in teleosts. The main objective of this study was to assess the effects of fadrozole, a powerful aromatase inhibitor, on gene expression in the zebrafish brain. To achieve this, male zebrafish were exposed to fadrozole for 10 days. This exposure causes a decrease in estrogens along with an increase in androgens. Plasma testosterone levels showed a 3-fold increase in response to the exposure. In the telencephalon, 235 genes were identified by Affymetrix GeneChip analysis as being differentially regulated. Real-time RT-PCR was used to validate the data obtained from the microarrays. This technique was also used to evaluate the response in the hypothalamus, which appears to follow similar transcriptional regulation. Gene ontology analysis of the microarray data revealed common biological processes and molecular functions such as sensory perception and detection of light stimulus, homeobox and transcription factor complexes. This study has identified genes which are directly and/or indirectly controlled by estrogens and androgens which helped to demonstrate the pronounced effects of endocrine disrupting chemicals on gene expression in the brain of teleosts. Collectively, the results provide a better understanding of the effects of aromatase inhibitors on gene expression and also shed light on the underlying effects of sex hormone variation and their importance in the brain of teleosts. Adult male zebrafish were exposed to fadrozole (200 ug/L) for 10 days. Telencephalons were pooled; approximately 30 per array. 3 treated samples, 3 control samples
2009-02-26 | E-GEOD-14718 | biostudies-arrayexpress
Project description:Cytochrome P450 aromatase is an essential enzyme for vertebrates. It is responsible for the conversion of androgens to estrogens in the brain and gonadal tissues. Aromatase converts testosterone into estradiol and therefore participates in the regulation of many processes which are controlled by estrogens such as development and fertility. Teleosts have been characterized as having exceptionally high levels of brain estrogen biosynthesis when compared to the brains of the other vertebrates. Little is known about the effects of estrogens on brain function in teleosts. The main objective of this study was to assess the effects of fadrozole, a powerful aromatase inhibitor, on gene expression in the zebrafish brain. To achieve this, male zebrafish were exposed to fadrozole for 10 days. This exposure causes a decrease in estrogens along with an increase in androgens. Plasma testosterone levels showed a 3-fold increase in response to the exposure. In the telencephalon, 235 genes were identified by Affymetrix GeneChip analysis as being differentially regulated. Real-time RT-PCR was used to validate the data obtained from the microarrays. This technique was also used to evaluate the response in the hypothalamus, which appears to follow similar transcriptional regulation. Gene ontology analysis of the microarray data revealed common biological processes and molecular functions such as sensory perception and detection of light stimulus, homeobox and transcription factor complexes. This study has identified genes which are directly and/or indirectly controlled by estrogens and androgens which helped to demonstrate the pronounced effects of endocrine disrupting chemicals on gene expression in the brain of teleosts. Collectively, the results provide a better understanding of the effects of aromatase inhibitors on gene expression and also shed light on the underlying effects of sex hormone variation and their importance in the brain of teleosts.
2009-02-26 | GSE14718 | GEO
Project description:To reveal the transcriptomic changes during the sex differetiation in larval zebrafish, we treated the lavarl fish with aromatase inhibitors (EM, CAS: 107868-30-4, 100 μg/L), as well as solvent as a control, and sampled them after the exposure.
2019-12-20 | GSE142353 | GEO
Project description:To identify the genes which have relation to aromatase-inhibitor-resistance, we compared the gene expression of aromatase-inhibitor-resistant cell, A3, with that of parent cell line, T-47D.
2014-04-01 | GSE51390 | GEO
Project description:To identify the genes which have relation to aromatase-inhibitor-resistance, we compared the gene expression of aromatase-inhibitor-resistant cell, A3, with that of parent cell line, T-47D. Because A3 showed remarkable cell proliferation by 1nM Dihydrotestosterone(DHT), cells were cultured with DHTand bicalutamide for 24h, and total RNA was extracted.
2014-04-01 | E-GEOD-51390 | biostudies-arrayexpress
Project description:Transcriptome of juvenile zebrafish treated with the aromatase inhibitor exemestane and solvent control
| PRJNA596870 | ENA
Project description:Understanding the complex molecular mechanisms underlying resistance to endocrine therapy is a major challenge in the treatment of estrogen receptor-positive (ER+) breast cancers. We have previously demonstrated that glial cell line-derived neurotrophic factor (GDNF) signaling via the receptor tyrosine kinase RET promotes estrogen independent activation of ER. Here we have addressed the relevance of GDNF-RET signaling in response to aromatase inhibitor treatment and explored the efficacy of using RET inhibitors in breast cancer models of aromatase inhibitor response and resistance. A GDNF-response gene set, identified from gene expression profiling, was demonstrated to be an independent prognostic marker of poor patient outcome and, importantly, to be predictive of poor response to aromatase inhibitor treatment and development of resistance. The relevance of these findings was validated first by demonstrating an association of RET protein expression in an independent cohort of aromatase inhibitor resistant patient samples. Second, in in vitro models, GDNF-mediated RET signaling was demonstrated to enhance the survival of aromatase inhibitor resistant cells and to increase resistance in aromatase inhibitor sensitive cells. These effects could be reversed by targeting GDNF/RET signaling with the RET selective inhibitor NVP-BBT594 thus identifying GDNF-RET signaling as a potential therapeutic target, particularly in breast cancers resistant to aromatase inhibitors.<br>MCF7 cells were E2-deprived by culturing in phenol red-free RPMI 1640 supplemented with 10% DCC for 3 days and then serum-starved overnight in the presence or absence of fulvestrant (ICI182,780) (100 nM). The following day, cells were treated with GDNF (20 ng/ml) for 0, 4, 8, 24 and 48 hours in the presence or absence of fulvestrant (ICI182,780) (100 nM).
2013-01-17 | E-MEXP-3662 | biostudies-arrayexpress
Project description:RNA-seq of adult zebrafish gonads in two sexes
| PRJNA596867 | ENA