Project description:Bisphenol S (BPS) is widely used to replace earlier-eliminated BPA. We evaluated the effect of acute in vivo BPS exposure on oocyte quality using eight-weeks-old ICR female mice (N = 15 per experimental group), exposed to vehicle or BPS1-BPS4 (0.001, 0.1, 10, and 100 ng BPS x g bw-1 x day-1, respectively). Oocytes were isolated and matured in vitro. Thereafter, we observed that BPS exposure increases aberrant spindle formation in mature oocytes and induces DNA damage. Moreover, BPS3 significantly increases chromatin repressive marks 5-methyl cytosine (5meC) and H3K27me2 in immature oocytes. In the BPS2 group (0.1 ng x g bw-1 x day-1), the increase in 5meC arises during oocyte maturation. Transcriptome analysis shows differential expression of early embryonic development transcripts in BPS2-exposed oocytes. These findings indicate that the biological effect of BPS is non-monotonic, affecting oocyte quality even at concentrations that are orders of magnitude below those measured in humans. We used microarray aproach to unravel gene expression differences triggered by the administration of BPS at different concentrations in mouse oocytes.
Project description:Bisphenol A (BPA) is used in the plastic industry as the monomer of polycarbonates and epoxy resins. Heat and changes in pH conditions lead to its leakage from the plastics in which it is incorporated. This largely contributes to the widespread exposure of the general population to this environmental contaminant. The exposure levels in humans are likely below the Tolerable Daily Intake (TDI: 50 µg/kg/day) and well below the No Observable Adverse Effect Level (NOAEL: 5000 µg/kg/day) defined from reprotoxicity studies. However, several studies suggest that BPA could induce deleterious effects specifically at low, environmentally relevant, doses. BPA has been described as an endocrine disruptor with estrogenic activity. Recently, it has been shown that BPA exposure has an impact on metabolic functions including stimulation of adipogenesis and of insulin production by the pancreas. Here, we investigated the effects of oral exposure to low (TDI) and high (NOAEL) doses of BPA on mouse liver transcriptome. Liver gene expression was measured from CD-1 mice (6 mice/group) exposed for 28 days to bisphenol A at doses 0 (controls), 50 (TDI or low dose) or 5000 µg/kg/day (NOAEL or high dose) via food contamination.
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:This study provides a comprehensive evaluation of changes in gene expression during treatment with Bisphenol A in vitro. Ishikawa cells were maintained and grown (to confluency or at a desired cell density between 500,000 - 1 million cells/mL) in DMEM/F-12 Medium (supplemented with 10% Fetal Bovine Serum + 1X penicillin/streptomycin) in xenoestrogen-free Corning plasticware. Cells were gently washed in warm PBS and transferred to phenol red-free DMEM/F-12 Medium (supplemented with 10% Charcoal-Stripped Fetal Bovine Serum + 1X penicillin/streptomycin) in Corning Cell Culture Cluster wells overnight and then challenged with 1pM (very low, vL), 100pM (low, L), 10nM (high, H), and 1uM (very high, vH) levels of BPA. Prior to collection, cells were washed in warm PBS, resuspended & briefly incubated in TRI-Reagent, & finally collected (in quintuplicate replicates) at each specific time point: 8 hours, 24 hours, and 48 hours. Following RNA isolation, the best RNA yields for each quadruplicate set was selected for target preparation and GeneChip processing. Keywords: Dose Response/Time Course
Project description:We are investigating the response of human lymphoblastoid cells to low-dose exposure of environmental metals We used microarrays to detail the global programme of gene expression upon response to low-dose metals Keywords: dose
Project description:To better understand the molecular basis of the reproductive health effects of bisphenol A (BPA) on humans, a genome-wide screening was applied to identify novel targets of low-dose bisphenol A exposure in huamn skin fibroblast cells (hSFCs) derived from hypospadias patient children. Three hSFCs were collected at National Research Institute for Child Health and Development, Japan. Gene expression profiles of hSFCs were measured at 24 hours after exposure to 10nM BPA, 0.01nM 17β-estradiol (E2) and 1nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Differentially expressed genes following chemical treatments were identified by unpaired Student’s t test with P values cut off by 0.05 and fold change of more than 1.2 and selected for the network generation and pathway analysis using Ingenuity Pathways Analysis (IPA) program. As the result, 71 genes (42 downregulated and 29 upregulated), 814 genes (371 downregulated and 443 upregulated), and 824 genes (344 downregulated and 480 upregulated) were identified significantly differently expressed in response to BPA, E2, and TCDD, respectively. The network analysis indicated that the most associated network fuctions of genes genes with altered expression profile derived from microarray analysis were “Endocrine System Disorders, Gastrointestinal Disease, Genetic Disorder”, “Cellular Growth and Proliferation, Skeletal and Muscular System Development and Function, Cell Cycle”, and “Post-Translational Modification, Genetic Disorder, Hematological Disease” in response to BPA, E2, and TCDD, respectively.
Project description:To better understand the molecular basis of the reproductive health effects of bisphenol A (BPA) on humans, a genome-wide screening was applied to identify novel targets of low-dose bisphenol A exposure in huamn skin fibroblast cells (hSFCs) derived from hypospadias patient children. Three hSFCs were collected at National Research Institute for Child Health and Development, Japan. Gene expression profiles of hSFCs were measured at 24 hours after exposure to 10nM BPA, 0.01nM 17β-estradiol (E2) and 1nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Differentially expressed genes following chemical treatments were identified by unpaired Student’s t test with P values cut off by 0.05 and fold change of more than 1.2 and selected for the network generation and pathway analysis using Ingenuity Pathways Analysis (IPA) program. As the result, 71 genes (42 downregulated and 29 upregulated), 814 genes (371 downregulated and 443 upregulated), and 824 genes (344 downregulated and 480 upregulated) were identified significantly differently expressed in response to BPA, E2, and TCDD, respectively. The network analysis indicated that the most associated network fuctions of genes genes with altered expression profile derived from microarray analysis were “Endocrine System Disorders, Gastrointestinal Disease, Genetic Disorder”, “Cellular Growth and Proliferation, Skeletal and Muscular System Development and Function, Cell Cycle”, and “Post-Translational Modification, Genetic Disorder, Hematological Disease” in response to BPA, E2, and TCDD, respectively. Gene expression profiles of 3 hSFCs derived from hypospadias patient children were measured at 24 hours after exposure to 10nM BPA, 0.01nM E2 and 1nM TCDD.
Project description:We are investigating the response of human lymphoblastoid cells to low-dose exposure of environmental metals We used microarrays to detail the global programme of gene expression upon response to low-dose metals Keywords: dose TK6 cells were grown to mid log-phase and exposed to low-doses of arsenic and cadmium. RNA was collected 24 hrs after exposure.