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Effects of long-term endocrine disrupting compound exposure on Macaca mulatta embryonic stem cells

ABSTRACT: 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.

ORGANISM(S): Macaca mulatta

PROVIDER: GSE86939 | GEO | 2016/09/15

SECONDARY ACCESSION(S): PRJNA343029

REPOSITORIES: GEO

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miRNA array of MCF-7 cells

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

2011-11-04 | E-GEOD-33481 | biostudies-arrayexpress

Changes in gene expression following long-term in vitro exposure of Macaca mulatta trophoblast stem cells to biologically relevant levels of endocrine disruptors

Project description:Trophoblast stem cells (TSCs) are key for embryo implantation and placentation. Environmental toxicants that compromise trophoblast function could compromise fetal viability, pregnancy outcome, and progeny health. Endocrine disrupting chemicals (EDCs) can epigenetically modify cells and alter their developmental properties. Understanding the effects of low, chronic EDC exposures on TSCs and pregnancy is a priority in developmental toxicology. Differences in placentation between primates and other mammals make a nonhuman primate model ideal for this. We examined effects of chronic low-level exposure to five EDCs on rhesus monkey TSCs in vitro. Two of the toxicants, ATR and TBT, exerted the strongest effects, with substantial overlap. Affected genes included some with obvious relevance to placentation and implantation (WNT7A, INHBA, and cytokines and their receptors). Pathway analysis revealed significant reductions in the expression of genes related to cytokine signaling, a feature shared across all five EDCs tested. Low-level chronic exposure of primate TSCs to EDCs may thus compromise trophoblast development in vivo, modify responses to pathogens and other challenges, and negatively affect embryo implantation and pregnancy rate.

2018-03-06 | GSE103033 | GEO

miRNA array of MCF-7 cells

2011-11-04 | GSE33481 | GEO

Genome-wide analysis of low dose bisphenol-A (BPA) exposure in human prostate cells

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.

2021-01-01 | E-MTAB-7576 | biostudies-arrayexpress

Consequences of perinatal bisphenol A exposure in a mouse model of multiple sclerosis

Project description:Multiple sclerosis (MS) is a complex disease influenced by genetic and environmental contributing factors. Endocrine disrupting compounds (EDCs) such as bisphenol A (BPA) affect gene expression and hormone-regulated systems throughout the body. We investigated the effects of BPA on Theiler’s-virus induced demyelination (TVID), a mouse model of MS. Perinatal BPA exposure, combined with viral infection, resulted in a decreased level of viral antibodies, accelerated the onset of TVID symptoms, increased inflammation in both the spinal cord and digestive tract, and amplified immune-related gene expression changes induced by viral infection. These results demonstrate the effect of BPA on the trajectory of TVID, and illustrate how multiple factors collectively influence autoimmune disease. For microarray: 7 samples

2013-08-01 | E-GEOD-46551 | biostudies-arrayexpress

Time-dependent transcriptomic responses of Daphnia magna exposed to metabolic disruptors that enhanced storage lipid accumulation.

Project description:Transcriptomic profiling of Daphnia magna samples exposed to tributyltin (TBT), pyriproxyfen (PP) and bisphenol A (BPA) at 8 and 24 hours. The analysis of lipid disruptive effects in invertebrates is limited by our poor knowledge of their lipidomes and of the associated metabolic pathways. Here we analyzed the subsequent transcriptome changes, using tributyltin (TBT), pyriproxyfen (PP) and bisphenol A (BPA). Changes in the whole transcriptome were assessed after 8 and 24 h of exposure, the period showing the greatest variation in storage lipid accumulation. The three compounds affected similarly to a total of 1388 genes (965 overexpressed and 423 underexpressed transcripts), but only after 24h of exposure. In addition,225 transcripts became up-regulated only in samples exposed to tributyltin for both 8h and 24 h. Using functional annotation from D. melanogaster, we determined that upregulated genes were enriched in members of KEGG modules implicated in fatty acid, phosphoinositol, glycerophospholipid, and glycerolipid metabolic pathways, as well as in genes related to membrane constituents , and to chitin and cuticle metabolic pathways. Conversely, down-regulated genes appeared mainly related with to visual perception, and to oocyte development signalling pathways. Many tributyltin specifically upregulated genes were related to neuro-active ligand receptor interaction signalling pathway. These changes are consistent with the previous observation that exposure of D. magna to the tested compounds increases lipid accumulation and reduces egg quality.

2019-09-01 | GSE119329 | GEO

EDCs gene expression profile in MCF7 cells

Project description:Endocrine disrupting chemicals (EDCs) are compounds that disrupt normal hormonal signaling. Examples are Xenoestrogens (e.g BPA) and Phytoestrogens (e.g isoflavones).

2013-12-31 | GSE45721 | GEO

Consequences of perinatal bisphenol A exposure in a mouse model of multiple sclerosis

2013-08-01 | GSE46551 | GEO

EDCs gene expression profile in MCF7 cells

Project description: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.

2013-12-31 | E-GEOD-45721 | biostudies-arrayexpress

Prenatal Bisphenol A Exposure in Mice Induces Multi-tissue Multi-omics Disruptions Linking to Cardiometabolic Disorders (RRBS)

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.

2018-10-23 | GSE121604 | GEO

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