ABSTRACT: Endocrine disrupting chemicals (EDCs) are compounds that disrupt normal hormonal signaling. Examples are Xenoestrogens (e.g BPA) and Phytoestrogens (e.g isoflavones). Comparison of EDC treated versus vehicle treated MCF7 parental cells. Each comparison in technical and biological duplicate.
Project description:Endocrine disrupting chemicals (EDCs) are compounds that disrupt normal hormonal signaling. Examples are Xenoestrogens (e.g BPA) and Phytoestrogens (e.g isoflavones).
Project description:Bisphenol A Exposure and Multiple Sclerosis Risk Comparison of vehicle-treated vs. BPA-treated mouse testes tissue. Each comparison in technical and biological duplicate (Done twice: total 4 replicates)
Project description:Background: Several environmental agents termed “endocrine disrupting compounds” or EDCs have been reported to bind and activate the estrogen receptor-a (ER). The EDCs DDT and BPA are ubiquitously present in the environment, and DDT and BPA levels in human blood and adipose tissue are detectable in most if not all women and men. ER-mediated biological responses can be regulated at numerous levels, including expression of coding RNAs (mRNAs) and more recently non-coding RNAs (ncRNAs). Of the ncRNAs, microRNAs have emerged as a target of estrogen signaling. Given the important implications of EDC-regulated ER function, we sought to define the effects of BPA and DDT on microRNA regulation and expression levels in estrogen-responsive human breast cancer cells. Methodology/Principal Findings: To investigate the cellular effects of DDT and BPA, we used the human MCF-7 breast cancer cell line, which is ER(+) and hormone sensitive. Our results show that DDT and BPA potentiate ER transcriptional activity, resulting in an increased expression of receptor target genes, including progesterone receptor, bcl-2, and trefoil factor 1. Interestingly, a differential increase in expression of Jun and Fas by BPA but not DDT or estrogen was observed. In addition to ER responsive mRNAs, we investigated the ability of DDT and BPA to alter the miRNA profiles in MCF-7 cells. While the EDCs and estrogen similarly altered the expression of multiple microRNAs in MCF-7 cells, including miR-21, differential patterns of microRNA expression were induced by DDT and BPA compared to estrogen. This experiment includes a total of 4 individual samples with no biological or technical repeats
Project description:Endocrine disrupting chemicals (EDCs) exert significant effects on health and physiology, many of which are traceable to effects on stem cell programming underlying organismal development. Understanding risk of low-level, chronic EDC exposure will be enhanced by knowledge of effects on stem cells. We exposed rhesus monkey embryonic stem cells to low levels of five different EDCs for 28 days, and evaluated effects on gene expression by RNAseq transcriptome profiling. EDCs tested included bisphenol A (BPA), atrazine (ATR), tributyltin (TBT), perfluorooctanoic acid (PFOA), and di-(2-ethylhexyl) phthalate (DEHP). We observed little effect of BPA, and small numbers of affected genes (119 or fewer) with the other EDCs. There was substantial overlap in effects across two, three, or four treatments. Ingenuity Pathway analysis indicated suppression of cell survival genes, activation of cell death genes, suppression of genes downstream of several stress response mediators, and modulations in several genes that regulate pluripotency, differentiation, and germ layer development. Potential adverse effects of these changes on development are discussed.
Project description:Endocrine disrupting compounds (EDCs) have the potential to cause adverse effects on wildlife and human health. Two important EDCs are the synthetic estrogen 17a-ethynylestradiol (EE2) and bisphenol A (BPA) both of which are xenoestrogens (XEs) as they bind the estrogen receptor and disrupt estrogen physiology in mammals and other vertebrates. In recent years the influence of XEs on oncogenes, specifically in relation to breast and prostate cancer has been the subject of considerable study. In this study healthy primary human prostate epithelial cells (PrECs) were exposed to environmentally relevant concentrations of BPA (5nM and 25nM BPA) and interrogated using a whole genome microarray. Microarray data were analyzed using the Pipeline for Integrated Microarray Expression and Normalization Toolkit (PIMENTo) that provides (1) data pre-processing, (2) and normalization to remove the technical variability across arrays data, (3) data visualization, (4) background subtraction, (5) quality control, and (6) differential expression (DE) analysis using the Bioconductor package 'limma'. Exposure to 5 and 25nM BPA generated 8,876 and 9,525 differentially expressed (DE) genes respectively in treated PrECs. Exposure to EE2 had the greatest effect on the PrEC transcriptome (2,389 DE genes) and all three exposures shared 7,011 common DE genes. Together, the low and high dose of BPA affected 1,839 genes not shared with the EE2 exposure.
Project description:Background: Several environmental agents termed “endocrine disrupting compounds” or EDCs have been reported to bind and activate the estrogen receptor-a (ER). The EDCs DDT and BPA are ubiquitously present in the environment, and DDT and BPA levels in human blood and adipose tissue are detectable in most if not all women and men. ER-mediated biological responses can be regulated at numerous levels, including expression of coding RNAs (mRNAs) and more recently non-coding RNAs (ncRNAs). Of the ncRNAs, microRNAs have emerged as a target of estrogen signaling. Given the important implications of EDC-regulated ER function, we sought to define the effects of BPA and DDT on microRNA regulation and expression levels in estrogen-responsive human breast cancer cells. Methodology/Principal Findings: To investigate the cellular effects of DDT and BPA, we used the human MCF-7 breast cancer cell line, which is ER(+) and hormone sensitive. Our results show that DDT and BPA potentiate ER transcriptional activity, resulting in an increased expression of receptor target genes, including progesterone receptor, bcl-2, and trefoil factor 1. Interestingly, a differential increase in expression of Jun and Fas by BPA but not DDT or estrogen was observed. In addition to ER responsive mRNAs, we investigated the ability of DDT and BPA to alter the miRNA profiles in MCF-7 cells. While the EDCs and estrogen similarly altered the expression of multiple microRNAs in MCF-7 cells, including miR-21, differential patterns of microRNA expression were induced by DDT and BPA compared to estrogen.
Project description:The health impacts of endocrine disrupting chemicals (EDCs) remain debated and their tissue and molecular targets are poorly understood. Here, we leveraged systems biology approaches to assess the target tissues, molecular pathways, and gene regulatory networks associated with prenatal exposure to the model EDC Bisphenol A (BPA). Prenatal BPA exposure led to scores of transcriptomic and methylomic alterations in the adipose, hypothalamus, and liver tissues in mouse offspring, with cross-tissue perturbations in lipid metabolism as well as tissue-specific alterations in histone subunits, glucose metabolism and extracellular matrix. Network modeling prioritized main molecular targets of BPA, including Pparg, Hnf4a, Esr1, Srebf1, and Fasn. Lastly, integrative analyses identified the association of BPA molecular signatures with cardiometabolic phenotypes in mouse and human. Our multi-tissue, multi-omics investigation provides strong evidence that BPA perturbs diverse molecular networks in central and peripheral tissues, and offers insights into the molecular targets that link BPA to human cardiometabolic disorders.
Project description:The health impacts of endocrine disrupting chemicals (EDCs) remain debated and their tissue and molecular targets are poorly understood. Here, we leveraged systems biology approaches to assess the target tissues, molecular pathways, and gene regulatory networks associated with prenatal exposure to the model EDC Bisphenol A (BPA). Prenatal BPA exposure led to scores of transcriptomic and methylomic alterations in the adipose, hypothalamus, and liver tissues in mouse offspring, with cross-tissue perturbations in lipid metabolism as well as tissue-specific alterations in histone subunits, glucose metabolism and extracellular matrix. Network modeling prioritized main molecular targets of BPA, including Pparg, Hnf4a, Esr1, Srebf1, and Fasn. Lastly, integrative analyses identified the association of BPA molecular signatures with cardiometabolic phenotypes in mouse and human. Our multi-tissue, multi-omics investigation provides strong evidence that BPA perturbs diverse molecular networks in central and peripheral tissues, and offers insights into the molecular targets that link BPA to human cardiometabolic disorders.
Project description:Comparison of the basal and estrogen-induced effects on genome-wide transcription in ERM-NM-1-positive breast cancer cell lines T47D and MCF7 after lentiviral transduction with ERM-NM-2. Comparison of ERM-NM-2-transduced T47D and MCF7 cells versus respective control-transduced cells, in the presence of vehicle or estrogen. Each comparison in technical and biological duplicate.
Project description:This submission is a part of two separate studies: a study of estrogen receptor-alpha (ERalpha)-mediated gene expression in response to different ligands and a study examining the roles of ERalpha and ERbeta in gene regulation in breast cancer cells. Comparison of estrogen-treated versus vehicle-treated MCF7 parental cells. Each comparison was performed in biological duplicate, with dye swapping.