Transcriptomal profiling of C57BL/6 wild type and ER-alpha KO mice fetal mammary gland after fetal exposure to Bisphenol A (BPA) and 17alpha-ethynylestradiol (EE2)
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE44387 | GEO | 2013/03/01
SECONDARY ACCESSION(S): PRJNA189718
REPOSITORIES: GEO
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Project description:To examine whether the BPA-induced morphological alterations of the fetal mouse mammary glands are a) associated with changes in mRNA expression reflecting estrogenic actions and/or b) dependent on the estrogen receptor α (ERα), we compared the transcriptomal effects of BPA and the steroidal estrogen ethinylestradiol (EE2) on fetal mammary tissues of wild type and ERα knock-out mice. Mammary glands from fetuses of dams exposed to vehicle, 250 ng BPA/kg BW/d or 10 ng EE2/kg BW/d from embryonic day (E) 8 were harvested at E19. Total RNA was subjected to transcriptomal profiling using Affymetrix mouse genome 430 2.0 microarray.
2013-03-01 | E-GEOD-44387 | biostudies-arrayexpress
Project description:Heat Shock Transcription Factor 1 (HSF1) is a well-known regulator of gene expression during acute environmental stress that enables the cells to survive. Its high level in estrogen receptor-positive breast cancer patients correlated with a worse prognosis. Here, we demonstrated that 17β-estradiol (E2) as well as bisphenol A (BPA) and propyl pyrazole triol (PPT, ERα agonist) led to HSF1 phosphorylation on S326 in ERα positive mammary breast cancer cells, but not in ERα-negative ones. We showed that ERK1/2 signaling was involved in this process and down-regulation of ERα expression abrogated it. E2activated HSF1 was transcriptionally potent. Chip-Seq and RNA-Seq analyses revealed that it could modulate the expression of several genes known to be essential for breast cancer cells growth and/or ERα action, i.e. HSPB8, LHX4, PRKCE, WWC1, and GREB1. Our findings indicate that a positive feedback loop between ERα and HSF1 signaling may exist which support the growth of estrogen-dependent tumors.
2019-10-05 | GSE137559 | GEO
Project description:Heat Shock Transcription Factor 1 (HSF1) is a well-known regulator of gene expression during acute environmental stress that enables the cells to survive. Its high level in estrogen receptor-positive breast cancer patients correlated with a worse prognosis. Here, we demonstrated that 17β-estradiol (E2) as well as bisphenol A (BPA) and propyl pyrazole triol (PPT, ERα agonist) led to HSF1 phosphorylation on S326 in ERα positive mammary breast cancer cells, but not in ERα-negative ones. We showed that ERK1/2 signaling was involved in this process and down-regulation of ERα expression abrogated it. E2activated HSF1 was transcriptionally potent. Chip-Seq and RNA-Seq analyses revealed that it could modulate the expression of several genes known to be essential for breast cancer cells growth and/or ERα action, i.e. HSPB8, LHX4, PRKCE, WWC1, and GREB1. Our findings indicate that a positive feedback loop between ERα and HSF1 signaling may exist which support the growth of estrogen-dependent tumors.
2019-10-05 | GSE137558 | GEO
Project description:Developmental exposure of mouse fetuses to estrogens results in dose-dependent permanent effects on prostate morphology and function. Fetal prostatic mesenchyme cells express estrogen receptor alpha (ERα) and androgen receptors and convert stimuli from estrogens and androgens into signaling to regulate epithelial cell proliferation and differentiation. To obtain mechanistic insight into the role of different doses of estradiol (E2) in regulating mesenchymal cells, we examined E2-induced transcriptomal changes in primary cultures of fetal mouse prostate mesenchymal cells. Urogenital sinus mesenchyme cells were obtained from male mouse fetuses at gestation day 17 and exposed to 10 pM, 100 pM or 100 nM E2 in the presence of a physiological concentration of dihydrotestosterone (0.69 nM) for four days. Gene ontology studies suggested that low doses of E2 (10 pM and 100 pM) induce genes involved in cell adhesion, morphological tissue development, and sterol biosynthesis but suppress genes involved in growth factor signaling and cell adhesion. Genes showing inverted-U-shape dose responses (enhanced by E2 at 10 pM E2 but suppressed at 100 pM) were identified, and their enrichment in the glycolytic pathway was demonstrated. At the highest dose (100 nM), E2 induced genes enriched not only for cell adhesion but also steroid hormone signaling and metabolism, cytokines and their receptors, cell-to-cell communication, Wnt signaling, and TGF-β signaling. These results suggest that prostate mesenchymal cells may regulate epithelial cells through direct cell contacts when estrogen level is low whereas soluble growth factors might play significant roles when estrogen level is high. Primary culture urogenital sinus mesenchymal cells were isolated from prostate glands of gestation day 17 CD1 male mouse fetuses. Cells were then exposed to 10 pM or 100 pM 17beta-estradiol or vehicle (0.05% ethanol) for four days in the presence of 690 pM 5alpha-dihydrotestosterone. Total cellular RNA was then isolated for determination of transcriptomal profiles by Affymetrix mouse gene 1.0 ST array.
2012-03-21 | E-GEOD-36630 | biostudies-arrayexpress
Project description:Developmental exposure of mouse fetuses to estrogens results in dose-dependent permanent effects on prostate morphology and function. Fetal prostatic mesenchyme cells express estrogen receptor alpha (ERα) and androgen receptors and convert stimuli from estrogens and androgens into signaling to regulate epithelial cell proliferation and differentiation. To obtain mechanistic insight into the role of different doses of estradiol (E2) in regulating mesenchymal cells, we examined E2-induced transcriptomal changes in primary cultures of fetal mouse prostate mesenchymal cells. Urogenital sinus mesenchyme cells were obtained from male mouse fetuses at gestation day 17 and exposed to 10 pM, 100 pM or 100 nM E2 in the presence of a physiological concentration of dihydrotestosterone (0.69 nM) for four days. Gene ontology studies suggested that low doses of E2 (10 pM and 100 pM) induce genes involved in cell adhesion, morphological tissue development, and sterol biosynthesis but suppress genes involved in growth factor signaling and cell adhesion. Genes showing inverted-U-shape dose responses (enhanced by E2 at 10 pM E2 but suppressed at 100 pM) were identified, and their enrichment in the glycolytic pathway was demonstrated. At the highest dose (100 nM), E2 induced genes enriched not only for cell adhesion but also steroid hormone signaling and metabolism, cytokines and their receptors, cell-to-cell communication, Wnt signaling, and TGF-β signaling. These results suggest that prostate mesenchymal cells may regulate epithelial cells through direct cell contacts when estrogen level is low whereas soluble growth factors might play significant roles when estrogen level is high.
2012-03-21 | GSE36630 | GEO
Project description:Estrogen receptor α (ERα) is the major driving transcription factor in normal mammary gland development as well as breast cancer initiation and progression.However,the fundamental mechanisms,including global cistromic and genomic transcriptional responses that are required to elicit mammary epithelial cell proliferation in response to ERα, have not been elucidated. We used chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) to identify estrogen regulated genes that directly recruit ERα in the WT mouse mammary gland
2019-07-23 | GSE129847 | GEO
Project description:Since initial regulatory action in 2010 in Canada, bisphenol A (BPA) has been progressively replaced by structurally related alternative chemicals. Unfortunately, many of these chemicals are data-poor, limiting toxicological risk assessment. We used high-throughput transcriptomics to evaluate potential hazards and compare potencies of BPA and 15 BPA alternative chemicals in cultured breast cancer cells. MCF-7 cells were exposed to BPA and 15 alternative chemicals (0.0005 – 100 µM) for 48 hrs. TempO-Seq sequencing (BioSpyder Inc.) was used to examine general toxicological effects and estrogen receptor alpha (ERα)-associated transcriptional changes. Benchmark concentration (BMC) analysis was conducted to identify two global transcriptomic points of departure (tPODs): (a) the lowest pathway median gene BMC and (b) the 25th lowest rank-ordered gene BMC. ERα activation was evaluated using a published transcriptomic biomarker and an ERα-specific tPOD was derived. Genes fitting BMC models were subjected to upstream regulator and canonical pathway analysis in Ingenuity Pathway Analysis. Biomarker analysis identified BPA and eight alternative chemicals as ERα active. Global and ERα tPODs produced highly similar potency rankings with BPAF as the most potent chemical tested, followed by BPA, BPC, 4,4’-BPF, BPAP, BPS, BADGE, 2,4’-BPF, Pergafast201®, D-8, 2,4’-BPS, TGSA, and BPS-MAE. Further, BPA and transcriptionally active alternative chemicals enriched similar gene sets associated with increased cell division and cancer-related processes. These data provide support for future read-across applications of transcriptomic profiling for risk assessment of data-poor chemicals and suggest that several BPA alternative chemicals may cause hazards at similar concentrations to BPA.
2022-08-18 | GSE211183 | GEO
Project description:Compairsion of transcriptional profiles of heart and skeletal muscle tissue of fetal rhesus monkey exposed to maternal Bisphenol A or vehicle during early or late gestaion. Maternal exposure to the endocrine disrupting chemical, bisphenol A (BPA) affects the development of multiple organ systems in rodents and monkeys. However, effects of BPA exposure on cardiac and skeletal muscle development have not been assessed. Given that maternal BPA crosses placenta and reaches developing fetus, examining the physiological consequences of gestational exposure during development is of research significance. Therefore, we evaluate the effects of daily, oral BPA exposure of pregnant rhesus monkeys (Macaca mulatta) on the fetal heart and skeletal muscle transcriptome. Pregnant monkeys were administered daily oral doses (400 µg/kg body weight) of BPA during early (50 –100 ± 2 days post conception, dpc) or late (100 ± 2 dpc - term), gestation. At the end of treatment, fetal heart tissues; left ventricle (LV), right ventricle (RV), left atrium (LA), right atrium (RA) and skeletal muscle; biceps femoris (BFM), were collected. Transcriptome expression was assessed using genome-wide microarray in each of the tissues and compared paired-wise between the BPA and matched control fetuses. Our results show that maternal BPA exposure alters transcriptional profile of several coding and non-coding genes in fetal heart and skeletal muscle.
2014-07-01 | GSE53393 | GEO
Project description:ERα is essential for the anti-proliferative response of breast cancer cells not only to estrogen antagonists, but also to estrogen withdrawal by means of aromatase inhibitors. We explored here one of the simplest explanation for this, consisting in the possibility that ERα may have a wide genomic function in absence of ligands. The genomic binding of ERα in the complete absence of estrogen was then studied using hormone-dependent MCF7 cells, by chromatin immunoprecipitation sequencing. From these data, 4.2K highly significant binding events were identified, which were further confirmed by comparing binding events in cells expressing ERα to cells silenced for ERα. Apo-ERα binding sites were distributed close to genes with functions associated to cell growth and epithelial maintenance and show significant overlap with binding of other transcription factors important for luminal epithelial breast cancer. Interestingly, we found that upon ERα silencing cognate gene transcription in absence of estrogen is downregulated and this is accompanied by increased H27Kme3 at ERα binding sites. RNA-Seq experiments showed that unliganded ERα controls basal transcription widely, including both coding and noncoding transcripts. Genes affected by ERα silencing can be easily functionally related to mammary epithelium differentiation and maintenance, especially when considering downregulated genes. Additional functions related to inflammatory and immune response was observed. Our data unravel unexpected actions of ERα in breast cancer cells and provide a novel framework to understand success and failure of hormone therapy in breast cancer. Examination of unligandend estrogen receptor alpha (aERα) DNA interactions in control and aERα siRNA treated MCF7 cells.
2014-03-03 | E-GEOD-53532 | biostudies-arrayexpress
Project description:Pharmaceutical compounds such as the non-steroidal anti-inflammatory drug ibuprofen and the artificial estrogen 17α-ethynylestradiol (EE2) are contaminants of emerging concern in freshwater systems. Globally, human pharmaceutical use is growing by around ~ 3% per year; yet, we know little about how interactions between different pharmaceuticals may affect aquatic ecosystems. Here, we test how interactions between ibuprofen and EE2 affect the growth and respiration of streambed biofilms. We used contaminant exposure experiments to quantify how these compounds affected biofilm growth (biomass), respiration, net primary production (NPP) and gross primary production (GPP), both individually and in combination. We found no effects of either ibuprofen or EE2 on biofilm biomass (using ash-free dry mass as a proxy) or gross primary production. Ibuprofen significantly reduced biofilm respiration and altered NPP. Concomitant exposure to EE2, however, counteracted the inhibitory effects of ibuprofen upon biofilm respiration. Our study, thus, demonstrates that interactions between pharmaceuticals in the environment may have complex effects upon microbial contributions to aquatic ecosystem functioning.
| S-EPMC7456402 | biostudies-literature