Anti-masculinization induced by aromatase inhibitors in adult female zebrafish
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ABSTRACT:
PROVIDER: PRJNA596764 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10741400_1.fastq.gz | Fastqsanger.gz | |||
| SRR10741400_2.fastq.gz | Fastqsanger.gz | |||
| SRR10741401_1.fastq.gz | Fastqsanger.gz | |||
| SRR10741401_2.fastq.gz | Fastqsanger.gz | |||
| SRR10741402_1.fastq.gz | Fastqsanger.gz |
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Project description:BACKGROUND:Early sex differentiation genes of zebrafish remain an unsolved mystery due to the difficulty to distinguish the sex of juvenile zebrafish. However, aromatase inhibitors (AIs) could direct juvenile zebrafish sex differentiation to male and even induce ovary-to-testis reversal in adult zebrafish. RESULTS:In order to determine the transcriptomic changes of sex differentiation in juvenile zebrafish and early sex-reversal in adult zebrafish, we sequenced the transcriptomes of juvenile and adult zebrafish treated with AI exemestane (EM) for 32 days, when juvenile zebrafish sex differentiation finished. EM treatment in females up-regulated the expression of genes involved in estrogen metabolic process, female gamete generation and oogenesis, including gsdf, macf1a and paqr5a, while down-regulated the expression of vitellogenin (vtg) genes, including vtg6, vtg2, vtg4, and vtg7 due to the lower level of Estradiol (E2). Furthermore, EM-juveniles showed up-regulation in genes related to cell death and apoptosis, such as bcl2l16 and anax1c, while the control-juveniles exhibited up-regulation of genes involved in positive regulation of reproductive process and oocyte differentiation such as zar1 and zpcx. Moreover, EM-females showed higher enrichment than control females in genes involved in VEGF signaling pathway, glycosaminoglycan degradation, hedgehog signaling pathway, GnRH signaling pathway and steroid hormone biosynthesis. CONCLUSIONS:Our study shows anti-masculinization in EM-treated adult females but not in EM-treated juveniles. This may be responsible for the lower sex plasticity in adults than juveniles.
| S-EPMC6947999 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-12-19 | GSE142355 | GEO
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:Anti-estrogens and aromatase inhibitors are important drugs in the treatment of estrogen-dependent breast cancer. In order to investigate the effects of these drugs on gene expression in breast cancer cells, we treated estrogen receptor-positive MCF-7 cells, stably transfected with the aromatase gene (known as MCF-7aro cells), with testosterone, 17β-estradiol, two aromatase inhibitors (letrozole and anastrozole), and an anti-estrogen (tamoxifen). Microarray analyses using Affymetrix Human Genome U133A GeneChips were carried out using total RNA isolated from the control and treated cells. When comparing the effect of each inhibitor on gene expression we observe that letrozole and anastrozole are more similar in terms of the genes they affect, compared to treatment with tamoxifen. The results of this study provide us with a better understanding of the actions of both aromatase inhibitors and anti-estrogens at the molecular level. We believe that the results of this study serve as the first step in identifying unique expression patterns following drug treatment, and that this will ultimately be useful in customizing patient treatment strategies for estrogen-dependent breast cancer. The data presented here have been processed using the R-Project Bioconductor statistical tools package using the affy library. The following were applied: RMA background correction, pmonly probe-level correction, quantile normalization, avgdiff summary method. Raw data is provided in the form of .CEL files.
2007-10-27 | E-GEOD-2225 | biostudies-arrayexpress
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: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:Fresh-frozen primary cancer specimens of 107 breast cancer patients whose metastases were treated with first-line aromatase inhibitors were evaluated for their whole genome mRNA expression profiles.
2013-12-05 | GSE41994 | 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.
2009-02-26 | GSE14718 | GEO
Project description:This study investigated whether undifferentiated germ and/or somatic stem cells remain in the differentiated ovary of a species that does not undergo sex changes under natural conditions and retain their sexual plasticity. The effect of aromatase inhibitor (AI)-treatment on sexually mature female zebrafish was examined. A 5-month AI treatment caused retraction of the ovaries after which testes-like organs appeared, and cyst structures filled with spermatozoa-like cells were observed in sections of these tissues. Electron microscopic observations revealed that these cells appeared as large sperm heads without tails. Sperm formation was re-examined after changing the diet to an AI-free food. A large number of normal sperm were obtained after eight weeks, and no formation of ovarian tissue was observed. Artificial fertilization using sperm from the sex-changed females was successful. These results demonstrated that sex plasticity remains in the mature ovaries of this species.
| S-EPMC3844967 | biostudies-literature
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