Rattus norvegicus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA139641 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Clinical trials of high-dose androgen therapy for prostate cancer have shown promising efficacy but are limited by lack of criteria to identify likely responders. To elucidate factors that govern the growth-repressive effects of high-dose androgens we applied an unbiased integrative approach utilizing genetic screens and transcriptional profiling of prostate cancer cells with or without demonstrated phenotypic sensitivity to androgen-mediated growth repression. Through this comprehensive analysis, we identified genetic events and related signaling networks that determine the response to both high-dose androgen and androgen withdrawal. We applied these findings to develop a gene signature that may serve as an early indicator of treatment response and identify men with tumors amenable to high dose androgen therapy.
2019-12-02 | GSE135879 | GEO
Project description:With the advent of high information content technologies, especially microarrays, it is pertinent to determine the impact of molecular data on the NOAELs. Consequently, we conducted an integrative study to identify a no transcriptomic effect dose using microarray analyses coupled with qPCR and determined how this correlated with the NOAEL. We assessed the testicular effects of the antiandrogen, flutamide (FM), in a rat 28-day toxicity study using doses of 0.2-30 mg/kg/day. Concerning molecular data, we observed differential gene expression starting from 1 mg/kg/day and a deregulation of more than 1500 genes at 30 mg/kg/day. Dose-related changes were identified for the major pathways associated with the testicular lesion (eg fatty acid metabolism), that were confirmed by qPCR. These data, along with standard measurements supported the no effect dose of 0.2 mg/kg/day. Flutamide was administered in suspension to rats (7 weeks old at start of treatment, 10 per group) by oral gavage at a daily dose of 0 (control), 0.2, 1, 6 and 30 mg/kg body weight, for 28 consecutive days. Dose-related changes in gene expression were determined in the testes using whole genome oligonucleotide microarrays.
2011-03-29 | E-GEOD-28202 | biostudies-arrayexpress
Project description:With the advent of high information content technologies, especially microarrays, it is pertinent to determine the impact of molecular data on the NOAELs. Consequently, we conducted an integrative study to identify a no transcriptomic effect dose using microarray analyses coupled with qPCR and determined how this correlated with the NOAEL. We assessed the testicular effects of the antiandrogen, flutamide (FM), in a rat 28-day toxicity study using doses of 0.2-30 mg/kg/day. Concerning molecular data, we observed differential gene expression starting from 1 mg/kg/day and a deregulation of more than 1500 genes at 30 mg/kg/day. Dose-related changes were identified for the major pathways associated with the testicular lesion (eg fatty acid metabolism), that were confirmed by qPCR. These data, along with standard measurements supported the no effect dose of 0.2 mg/kg/day.
2011-03-29 | GSE28202 | GEO
Project description:Linking genomic variation to phenotypical traits remains a major challenge in evolutionary genetics. In this study, we use phylogenomic strategies to investigate a distinctive trait among mammals: the development of masculinizing ovotestes in female moles. By combining a chromosome-scale genome assembly of the Iberian mole, Talpa occidentalis, with transcriptomic, epigenetic, and chromatin interaction datasets, we identify rearrangements altering the regulatory landscape of genes with distinct gonadal expression patterns. These include a tandem triplication involving CYP17A1, a gene controlling androgen synthesis, and an intrachromosomal inversion involving the pro-testicular growth factor FGF9, which is heterochronically expressed in mole ovotestes. Transgenic mice with a knock-in mole CYP17A1 enhancer or overexpressing FGF9 showed phenotypes recapitulating mole sexual features. Our results highlight how integrative genomic approaches can reveal the phenotypic impact of noncoding sequence changes.
2020-10-09 | GSE136333 | GEO
Project description:Linking genomic variation to phenotypical traits remains a major challenge in evolutionary genetics. In this study, we use phylogenomic strategies to investigate a distinctive trait among mammals: the development of masculinizing ovotestes in female moles. By combining a chromosome-scale genome assembly of the Iberian mole, Talpa occidentalis, with transcriptomic, epigenetic, and chromatin interaction datasets, we identify rearrangements altering the regulatory landscape of genes with distinct gonadal expression patterns. These include a tandem triplication involving CYP17A1, a gene controlling androgen synthesis, and an intrachromosomal inversion involving the pro-testicular growth factor FGF9, which is heterochronically expressed in mole ovotestes. Transgenic mice with a knock-in mole CYP17A1 enhancer or overexpressing FGF9 showed phenotypes recapitulating mole sexual features. Our results highlight how integrative genomic approaches can reveal the phenotypic impact of noncoding sequence changes.
2020-10-09 | GSE120589 | GEO
Project description:Linking genomic variation to phenotypical traits remains a major challenge in evolutionary genetics. In this study, we use phylogenomic strategies to investigate a distinctive trait among mammals: the development of masculinizing ovotestes in female moles. By combining a chromosome-scale genome assembly of the Iberian mole, Talpa occidentalis, with transcriptomic, epigenetic, and chromatin interaction datasets, we identify rearrangements altering the regulatory landscape of genes with distinct gonadal expression patterns. These include a tandem triplication involving CYP17A1, a gene controlling androgen synthesis, and an intrachromosomal inversion involving the pro-testicular growth factor FGF9, which is heterochronically expressed in mole ovotestes. Transgenic mice with a knock-in mole CYP17A1 enhancer or overexpressing FGF9 showed phenotypes recapitulating mole sexual features. Our results highlight how integrative genomic approaches can reveal the phenotypic impact of noncoding sequence changes.
2020-10-09 | GSE120587 | GEO
Project description:Linking genomic variation to phenotypical traits remains a major challenge in evolutionary genetics. In this study, we use phylogenomic strategies to investigate a distinctive trait among mammals: the development of masculinizing ovotestes in female moles. By combining a chromosome-scale genome assembly of the Iberian mole, Talpa occidentalis, with transcriptomic, epigenetic, and chromatin interaction datasets, we identify rearrangements altering the regulatory landscape of genes with distinct gonadal expression patterns. These include a tandem triplication involving CYP17A1, a gene controlling androgen synthesis, and an intrachromosomal inversion involving the pro-testicular growth factor FGF9, which is heterochronically expressed in mole ovotestes. Transgenic mice with a knock-in mole CYP17A1 enhancer or overexpressing FGF9 showed phenotypes recapitulating mole sexual features. Our results highlight how integrative genomic approaches can reveal the phenotypic impact of noncoding sequence changes.
2020-10-09 | GSE120586 | GEO
Project description:Linking genomic variation to phenotypical traits remains a major challenge in evolutionary genetics. In this study, we use phylogenomic strategies to investigate a distinctive trait among mammals: the development of masculinizing ovotestes in female moles. By combining a chromosome-scale genome assembly of the Iberian mole, Talpa occidentalis, with transcriptomic, epigenetic, and chromatin interaction datasets, we identify rearrangements altering the regulatory landscape of genes with distinct gonadal expression patterns. These include a tandem triplication involving CYP17A1, a gene controlling androgen synthesis, and an intrachromosomal inversion involving the pro-testicular growth factor FGF9, which is heterochronically expressed in mole ovotestes. Transgenic mice with a knock-in mole CYP17A1 enhancer or overexpressing FGF9 showed phenotypes recapitulating mole sexual features. Our results highlight how integrative genomic approaches can reveal the phenotypic impact of noncoding sequence changes.
2020-10-09 | GSE120583 | GEO
Project description:Linking genomic variation to phenotypical traits remains a major challenge in evolutionary genetics. In this study, we use phylogenomic strategies to investigate a distinctive trait among mammals: the development of masculinizing ovotestes in female moles. By combining a chromosome-scale genome assembly of the Iberian mole, Talpa occidentalis, with transcriptomic, epigenetic, and chromatin interaction datasets, we identify rearrangements altering the regulatory landscape of genes with distinct gonadal expression patterns. These include a tandem triplication involving CYP17A1, a gene controlling androgen synthesis, and an intrachromosomal inversion involving the pro-testicular growth factor FGF9, which is heterochronically expressed in mole ovotestes. Transgenic mice with a knock-in mole CYP17A1 enhancer or overexpressing FGF9 showed phenotypes recapitulating mole sexual features. Our results highlight how integrative genomic approaches can reveal the phenotypic impact of noncoding sequence changes.
2020-10-09 | GSE120582 | 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