Rattus norvegicus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA277505 | ENA |
REPOSITORIES: ENA
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Project description:Exposure of humans to bisphenol A (BPA) is widespread and continuous. We previously showed that perinatal exposure to BPA increased prostate cancer risk in adult rats. Yet the effects of protracted, exposure to BPA during adulthood have not been studied. In this study, we subjected Noble rats to 32 weeks of co-treatment with testosterone (T) and BPA (low- or high-dose) or T and 17β-estradiol (E2) via Silastic capsule implants. Circulating T levels were comparable in all treatment groups, whereas the levels of free BPA were elevated in the groups that received T+low BPA (1.06 ± 0.05 ng/ml, P<0.05) and T+high BPA (10.37 ± 0.43 ng/ml, P<0.01) when compared with those in controls (0.1 ± 0.05 ng/ml). T+low/high BPA induced prostatic hyperplasia, low-grade prostatic intraepithelial neoplasia (PIN), and intraepithelial infiltration of T-lymphocytes only in the lateral prostates (LPs), whereas T+E2 induced high-grade PIN in this prostatic lobe. Genome-wide transcriptome analysis identified differential changes in the LPs of T+BPA and T+E2 treatments, with aberrant expression of multiple genes in the regulatory network controlled by the transcription factor hepatic nuclear factor 4α (HNF4α) specifically in BPA- but not E2-treated LPs. These findings suggest that the adult rat prostate is susceptible to transcriptomic reprogramming by BPA associated with the development of prostate pathology in a manner distinct from that of E2. The relevance of these data to the previous report demonstrating an association between high urinary levels of BPA and prostate cancer needs to be studied further.
2015-03-07 | GSE66633 | GEO
Project description:Bisphenol A (BPA) is primarily used to make polycarbonate plastic, with a global capacity of production exceeding 8 million tons per year. Biomonitoring studies with human urine, blood and tissue samples suggest that humans are subjected to widespread and continuous exposure to BPA. It has been well established that early life exposure to BPA predisposes the prostate gland to carcinogenesis later in life. However, it remains unknown if BPA exposure during adulthood induces benign or neoplastic pathology in the prostate. The main objective of the present study is to determine the effects of BPA exposures during adulthood on the prostate and to characterize the global transcriptional reprogramming underlying endocrine disruption by BPA. We elevated circulating levels of free BPA in Noble rats to the human-relevant internal dose range with BPA-filled Silastic implants while maintaining the physiological levels of testosterone (T) with T-filled implants. Cotreatment with T and 17β-estradiol (E2) was our reference regimen which induced preneoplastic and cancereous lesions. The T + low/high dose of BPA induced prostatic hyperplasia, low-grade prostate intraepithelial neoplasia (LGPIN) and intraepithelial infiltration of T-lymphocytes specifically in the lateral prostate (LP). Using microarray analysis, we delineated specific impacts of low and high dose of BPA (with the T-support) on the gene expression program in LPs. Hierarchical clustering revealed that the endocrine disrupting effects of T + low dose of BPA showed partial resemblance to those of T + high dose of BPA and T+E2. In contrast, the influence of T+ high dose of BPA on the LP transcriptome was completely different from those of T + E2. Further, IPA analysis of specific T+ low or high BPA gene signature identified a transcription factor, HNF4α, as a regulatory hub affecting a number of differentially expressed genes by BPA exposures. These findings suggest that the adult rat prostate is still venerable to the endocrine disrupting effects of BPA. Perhaps chronic exposure to low dose of BPA provides a niche comprising heightened cell proliferation, inflammatory responses and disrupted gene expression program, which favor the onset and development of prostatic benign or malignant diseases in men. Rat lateral prostates were collected from untreated control and treated groups [Testosterone (T) + Estradiol (E2), T + low dose Bisphenol A (low BPA) and T + high BPA] for RNA extraction and hybridization on Affymetrix microarrays. We sought to identify transcriptional signature of BPA exposures in the lateral prostate gland.
2015-03-07 | E-GEOD-66633 | biostudies-arrayexpress
Project description:Gene expression microarray analysis was performed on ventral prostate from normal adult rats, and adult rats treated BPA for 4 weeks(10 animals per group). Animals of 4 groups were treated with bisphenol-A (0,10, 30, or 90 ug/kg, i.g., daily) for 4 weeks, and the dosing volume is 10 ml/kg body weight. In this experiment, we only selected samples from two doses(0 and 10µg/kg) to analyze.
2014-01-15 | E-MTAB-2181 | biostudies-arrayexpress
Project description:We generated a novel Six2-Cre+/-PKAcaRfl/wt (CA-PKA) CA-PKA mouse in which expression of constitutive-active PKAcaR was induced in gastric mesenchyme progenitors. CA-PKA mice showed disruption of gastric homeostasis characterized by aberrant mucosal development and epithelial hyperproliferation; ultimately developing multiple features of gastric corpus preneoplasia including decreased parietal cells, mucous cell hyperplasia, spasmolytic peptide expressing metaplasia (SPEM) with intestinal characteristics and dysplastic and invasive cystic glands. Our results show that constitutively active PKAcaR in the stomach mesenchyme nonautonomously disrupts gastric homeostasis characterized by increased epithelial proliferation and aberrant epithelial maldevelopment, ultimately leading to gastric preneoplasia.
2022-09-20 | GSE196236 | GEO
Project description:Emerging evidence suggests that estrogen and prolactin (PRL) play a key role in prostate cancer development, yet their relationship and molecular actions in prostate is not well understood. To address this issue, we made the first direct comparison of estrogen and PRL actions in the Noble rat (NBL) prostate dysplasia model.
2010-05-09 | GSE17819 | GEO
Project description:Hepatocyte Nuclear Factor 4α (HNF4α), master regulator of hepatocyte differentiation, is regulated by two promoters (P1 and P2). P1-HNF4α but not P2-HNF4α is expressed in normal adult liver while both P1- and P2-HNF4α are expressed in fetal liver and liver cancer. To determine the physiological function of the HNF4α isoforms, we compared P2-HNF4α-expressing exon swap mice to wildtype (WT) using RNA-seq, ChIP-seq, proteomics, protein binding microarrays (PBMs) and metabolomics. P2-HNF4α orchestrates a distinct transcriptomic and metabolomic profile.
2018-08-31 | GSE117972 | GEO
Project description:Bisphenol A is an environmental xenoestrogen commonly known as an endocrine disruptor. We previously reported BPA-treated human primary prostate epithelial cell derived prostaspheres had larger size, exhibited clonogenicity, and showed increase in stem cell marker expression. Results reveal the molecular basis of BPA action in human prostate stem-progenitor cells. Human primary prostate epithelial cells from three disease-free Caucasian donors formed prostaspheres from single stem-like cells in matrigel cultures and were treated with 0.1 nM estradiol-17β (E2), 10 nM (B10), 200 nM (B200), and 1000 nM bisphenol A (BPA) for 7 days. The vehicle-treated prostaspheres were used as 'untreated controls'.
2014-11-05 | E-GEOD-62953 | biostudies-arrayexpress
Project description:Hepatocyte Nuclear Factor 4α (HNF4α), master regulator of hepatocyte differentiation, is regulated by two promoters (P1 and P2). P1-HNF4α but not P2-HNF4α is expressed in normal adult liver in fed conditions. Both P1- and P2-HNF4α are expressed in fetal liver. P2-HNF4α expression is increased in fasted conditions, high fat diet, alcoholic liver and liver cancer. To determine the target genes of the P1- and P2-HNF4α isoforms, we compared P2-HNF4α-expressing exon swap mice (a7HMZ) to wildtype (WT) male mice. Liver ChIP-seq samples were taken at 10:30 AM (ZT 3.5)
2023-05-10 | GSE231538 | GEO
Project description:Background & Aims: The role of HNF4α has been extensively studied in hepatocytes and pancreatic β cells, but emerging evidence indicates that HNF4α is a key regulator of intestinal epithelial cell differentiation as well. The aim of the present work is to identify HNF4α target genes in the intestine in order to elucidate the role of HNF4α in differentiation of the intestinal epithelial cells. Results: One thousand one hundred and seventy-six genes were identified as HNF4α targets, many of which have not previously been described as being regulated by HNF4α. The 1,176 genes contributed significantly to gene ontology (GO) pathways categorized by lipid and amino acid transport and metabolism. A thorough analysis of Cdx-2, trehalase, and cingulin promoters verified that these genes are regulated by HNF4α. In each case we were able to identify a functional HNF4α binding site in their promoters. Conclusions: HNF4α regulation of the Cdx-2 promoter unravels a transcription factor network also including HNF1α and β, all of which are transcription factors involved in intestinal development and gene expression. Keywords: ChIP-CHIP and expression data
2007-05-10 | GSE7745 | GEO
Project description:Treatment of mice with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been shown to disrupt many physiological processes including hepatic lipid metabolism, bile acid homeostasis, glucose metabolism, iron and heme homeostasis, and one-carbon metabolism. TCDD disrupts these metabolic pathways mediated by the aryl hydrocarbon receptor (AhR). We have previously shown that the AhR localizes to genomic regions possessing DNA motifs that also contain binding sites for other transcription factors, implicating potential co-operation between the AhR and these other transcription factors in the regulation of target genes. Two possible co-operating transcription factors include HNF4α and COUP-TFII. To investigate interactions between AhR, HNF4α and COUP-TFII hepatic ChIP-seq analysis was performed for HNF4α and COUP-TFII mice treated with TCDD for 2 hours, to supplement pre-existing AhR ChIP-seq data. ChIP-seq analysis revealed genome-wide changes in COUP-TFII and HNF4α binding following treatment with TCDD, with 11,688 and 9,547 genomic regions possessing differential enrichment, respectively. These differentially enriched regions for COUP-TFII and HNF4α fell within the intragenic region of 6,846 and 5,762 genes, respectively. When supplemented with pre-existing AhR ChIP-seq data, AhR, HNF4α and COUP-TFII were found to co-bind to the intragenic region of 6,376 genes.
2021-08-03 | GSE178168 | GEO