In vivo effects of short-term treatment with Bisphenol A (BPA) on mice pancreatic islets
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE126297 | GEO | 2019/02/09
REPOSITORIES: GEO
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Project description:Bisphenol A (BPA) is a common industrial chemical widely used to produce various plastics and is known to impair neural stem cells (NSCs). However, the effects of low-dose BPA exposure on the stemness maintenance and differentiation fate of NSCs remain unclear in the infants brain. Here we demonstrated that 1 μM BPA promoted human NSC proliferation and stemness, and didn’t significantly increase cell apoptosis. The Chip-seq experiments demonstrated that both the cell cycle and the TGF-beta signaling pathway were accelerated under the 1 μM BPA condition.
2021-10-03 | GSE185138 | GEO
Project description:Bisphenol A (BPA) is a widespread Endocrine Disrupter mainly used in food contact plastics. Several evidences support BPA adverse effects, especially on susceptible groups such as pregnant women. The present study considered placental development - relevant for pregnancy outcomes and fetal nutrition/programming - as a potential target of BPA. Pregnant CD-1 mice were administered per os with vehicle, 0.5 (BPA05) or 50 mg/kg (BPA50) body weight (bw)/die of BPA, from gestational day (GD) 1 to GD11. At GD12, BPA50 induced significant degeneration and necrosis of giant cells, increased vacuolization in the junctional zone in absence of glycogen accumulation and reduction of the spongiotrophoblast layer. BPA05 induced a significant nuclear accumulation of β-catenin in trophoblasts of the labyrinthine and spongiotrophoblast layers, supporting an activation of the Wnt/β-catenin pathway. Transcriptomic analysis indicated a BPA05 promotion and a BPA50 inhibition of blood vessels development and branching supported by the morphological observation of decreased and increased total vessels area in the labyrinth layers upon BPA05 and BPA50 treatments, respectively, with BPA50 also inducing a decrease in vessels number. These mechanisms involve, respectively, CREB and Wnt/β-catenin pathways for BPA05 and AhR/ARNT pathway for BPA50, as deducted by the transcription factor binding analysis. These results show that BPA differently affects mouse placental development depending on the dose level. In particular, the 0.5 mg/kw bw, in the range of dose level used to set the Tolerable Daily Intake, may elicit not negligible alterations whose relevance for human health has to be carefully evaluated.
2014-12-15 | GSE63852 | GEO
Project description:Environmental compounds are known to promote epigenetic transgenerational inheritance of adult onset disease in subsequent generations (F1–F3) following ancestral exposure during fetal gonadal sex determination. The current study was designed to determine if a mixture of plastic derived endocrine disruptor compounds bisphenol-A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and dibutyl phthalate (DBP) at two different doses promoted epigenetic transgenerational inheritance of adult onset disease and associated DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to either the “plastics” or “lower dose plastics” mixture during embryonic days 8 to 14 of gonadal sex determination and the incidence of adult onset disease was evaluated in F1 and F3 generation rats. There were significant increases in the incidence of total disease/abnormalities in F1 and F3 generation male and female animals from plastics lineages. Pubertal abnormalities, testis disease, obesity, and ovarian disease (primary ovarian insufficiency and polycystic ovaries) were increased in the F3 generation animals. Kidney and prostate disease were only observed in the direct fetally exposed F1 generation plastic lineage animals. Analysis of the plastics lineage F3 generation sperm epigenome previously identified 197 differential DNA methylation regions (DMR) in gene promoters, termed epimutations. A number of these transgenerational DMR form a unique direct connection gene network and have previously been shown to correlate with the pathologies identified. Observations demonstrate that a mixture of plastic derived compounds, BPA and phthalates, can promote epigenetic transgenerational inheritance of adult onset disease. The sperm DMR provide potential epigenetic biomarkers for transgenerational disease and/or ancestral environmental exposures.
2014-07-22 | GSE59555 | GEO
Project description:Bisphenol A (BPA) is a widespread Endocrine Disrupter mainly used in food contact plastics. Several evidences support BPA adverse effects, especially on susceptible groups such as pregnant women. The present study considered placental development - relevant for pregnancy outcomes and fetal nutrition/programming - as a potential target of BPA. Pregnant CD-1 mice were administered per os with vehicle, 0.5 (BPA05) or 50 mg/kg (BPA50) body weight (bw)/die of BPA, from gestational day (GD) 1 to GD11. At GD12, BPA50 induced significant degeneration and necrosis of giant cells, increased vacuolization in the junctional zone in absence of glycogen accumulation and reduction of the spongiotrophoblast layer. BPA05 induced a significant nuclear accumulation of M-NM-2-catenin in trophoblasts of the labyrinthine and spongiotrophoblast layers, supporting an activation of the Wnt/M-NM-2-catenin pathway. Transcriptomic analysis indicated a BPA05 promotion and a BPA50 inhibition of blood vessels development and branching supported by the morphological observation of decreased and increased total vessels area in the labyrinth layers upon BPA05 and BPA50 treatments, respectively, with BPA50 also inducing a decrease in vessels number. These mechanisms involve, respectively, CREB and Wnt/M-NM-2-catenin pathways for BPA05 and AhR/ARNT pathway for BPA50, as deducted by the transcription factor binding analysis. These results show that BPA differently affects mouse placental development depending on the dose level. In particular, the 0.5 mg/kw bw, in the range of dose level used to set the Tolerable Daily Intake, may elicit not negligible alterations whose relevance for human health has to be carefully evaluated. Three conidtions experiment: Control, BPA 0.5 mg/kg bw die; BPA 50 mg/kg bw die. Biological replicates: three control replicates; four replicates per treatment. Technical replicates: 2 (dye swap) per biological replica
2014-12-15 | E-GEOD-63852 | biostudies-arrayexpress
Project description:Bisphenol A (BPA), a widely used chemical in the manufacture of plastics and epoxy resins, is prevalent in the aquatic environment and disrupts endocrine pathways in fish, but the long-term developmental implications are unknown. We demonstrate that BPA in eggs of rainbow trout (Oncorhynchus mykiss), a commercially important species of fish with a long life-cycle, has the potential to reprogram liver metabolism in the offspring and alter the developmental growth phenotype in multiple generations. Specifically, BPA reduces growth during early development, followed by a catch-up growth and obesity phenotype in juveniles. More importantly, we observed a shift in the liver transcripts supporting the transient growth phenotypes observed in the F1 generation and this was also evident in the F2 generation. These results reveal that maternal and/or ancestral exposure to BPA in eggs has long-lasting and multigenerational impacts in trout, with implications on salmonid fisheries and sustainability of ecosystem health.
2017-01-31 | GSE94281 | GEO
Project description:Xenoestrogens are part of a group of agents termed endocrine disruptors because of their capacity to perturb normal hormonal actions. It has been suggested that xenoestrogens may contribute to the development of hormone-dependent cancers, such as breast and endometrial cancers. Bisphenol A (BPA) is polymerized to manufacture polycarbonate plastic and epoxy resins. Human exposure occurs when BPA leaches from plastic-lined food and beverage cans. In the present work we are aiming to determine if BPA has carcinogenic properties by using an in vitro system. For this purpose the human breast epithelial cells MCF-10F were treated with 10-3M to 10-9M BPA continuously for two weeks. The MCF-10F cells treated with 10-3M and 10-4M BPA died, indicating that these concentrations were toxic for the human breast epithelial cells. The cells treated with 10-5M to 10-9M BPA were evaluated for formation of solid masses in collagen and invasion capacity, both phenotypes that are indicators of cell transformation. MCF-10F treated with 10-5M, 10-6M, 10-7M, 10-8M and 10-9M BPA formed a high percentage of solid masses (34.6%, 20%, 42.4%, 31.8% and 32.2%, respectively). Ten passages after BPA treatments, the invasive capacities of the cells were evaluated using Boyden chambers. The invasion capacity was lower in the cells treated at high concentrations of BPA (10-5M and 10-6M), and there was an increased invasion for the cells treated at low BPA concentration (10-9M) although, in all the cases the differences were not significant to the controls. Expression and DNA methylation analyses were performed with the cells treated with 10-5M and 10-6M BPA. We found that these cells showed an increased expression of BRCA1, BARD1, CtIP, RAD51 and BRCC3, all genes involved in DNA repair, and downregulation of PDCD5 and BCL2L11 (also known as BIM), both involved in apoptosis. The upregulation of CtIP was related to hypomethylation of the promoter/exon1 of this gene. Furthermore, BPA induced silencing of BCL2L11 by hypermethylation. This is the first demonstration that BPA induces neoplastic transformation of breast epithelial cells and that aberrant DNA methylation of genes involved in DNA repair and apoptosis could be involved in the initiation of the neoplastic process.
2011-03-10 | GSE27865 | GEO
Project description:Xenoestrogens are part of a group of agents termed endocrine disruptors because of their capacity to perturb normal hormonal actions. It has been suggested that xenoestrogens may contribute to the development of hormone-dependent cancers, such as breast and endometrial cancers. Bisphenol A (BPA) is polymerized to manufacture polycarbonate plastic and epoxy resins. Human exposure occurs when BPA leaches from plastic-lined food and beverage cans. In the present work we are aiming to determine if BPA has carcinogenic properties by using an in vitro system. For this purpose the human breast epithelial cells MCF-10F were treated with 10-3M to 10-9M BPA continuously for two weeks. The MCF-10F cells treated with 10-3M and 10-4M BPA died, indicating that these concentrations were toxic for the human breast epithelial cells. The cells treated with 10-5M to 10-9M BPA were evaluated for formation of solid masses in collagen and invasion capacity, both phenotypes that are indicators of cell transformation. MCF-10F treated with 10-5M, 10-6M, 10-7M, 10-8M and 10-9M BPA formed a high percentage of solid masses (34.6%, 20%, 42.4%, 31.8% and 32.2%, respectively). Ten passages after BPA treatments, the invasive capacities of the cells were evaluated using Boyden chambers. The invasion capacity was lower in the cells treated at high concentrations of BPA (10-5M and 10-6M), and there was an increased invasion for the cells treated at low BPA concentration (10-9M) although, in all the cases the differences were not significant to the controls. Expression and DNA methylation analyses were performed with the cells treated with 10-5M and 10-6M BPA. We found that these cells showed an increased expression of BRCA1, BARD1, CtIP, RAD51 and BRCC3, all genes involved in DNA repair, and downregulation of PDCD5 and BCL2L11 (also known as BIM), both involved in apoptosis. The upregulation of CtIP was related to hypomethylation of the promoter/exon1 of this gene. Furthermore, BPA induced silencing of BCL2L11 by hypermethylation. This is the first demonstration that BPA induces neoplastic transformation of breast epithelial cells and that aberrant DNA methylation of genes involved in DNA repair and apoptosis could be involved in the initiation of the neoplastic process.
2011-09-16 | GSE32158 | GEO
Project description:Xenoestrogens are part of a group of agents termed endocrine disruptors because of their capacity to perturb normal hormonal actions. It has been suggested that xenoestrogens may contribute to the development of hormone-dependent cancers, such as breast and endometrial cancers. Bisphenol A (BPA) is polymerized to manufacture polycarbonate plastic and epoxy resins. Human exposure occurs when BPA leaches from plastic-lined food and beverage cans. In the present work we are aiming to determine if BPA has carcinogenic properties by using an in vitro system. For this purpose, the human breast epithelial cells MCF-10F were treated with 10-3M to 10-9M BPA continuously for two weeks. The MCF-10F cells treated with 10-3M and 10-4M BPA died, indicating that these concentrations were toxic for the human breast epithelial cells. The cells treated with 10-5M to 10-9M BPA were evaluated for formation of solid masses in collagen and invasion capacity, both phenotypes that are indicators of cell transformation. MCF-10F treated with 10-5M, 10-6M, 10-7M, 10-8M and 10-9M BPA formed a high percentage of solid masses (34.6%, 20%, 42.4%, 31.8% and 32.2%, respectively). Ten passages after BPA treatments, the invasive capacities of the cells were evaluated using Boyden chambers. The invasion capacity was lower in the cells treated at high concentrations of BPA (10-5M and 10-6M), and there was an increased invasion for the cells treated at low BPA concentration (10-9M), although in all the cases the differences were not significant to the controls. Expression and DNA methylation analysis were performed with the cells treated with 10-5M and 10-6M BPA. We found that these cells showed an increased expression of BRCA1, BARD1, CtIP, RAD51 and BRCC3, all genes involved in DNA repair, and downregulation of PDCD5 and BCL2L11 (also known as BIM), both involved in apoptosis. The upregulation of CtIP was related to hypomethylation of the promoter/exon1 of this gene. Furthermore, BPA induced silencing of BCL2L11 by hypermethylation. This is the first demonstration that BPA induces neoplastic transformation of breast epithelial cells and that aberrant DNA methylation of genes involved in DNA repair and apoptosis could be involved in the initiation of the neoplastic process.
2011-02-28 | GSE26884 | GEO
Project description:Aim: Identify Ambra1-dependent regulation in melanoma development by comparing bulk RNA extracted from Ambra1-depleted (BPA-/-) mouse melanomas to Ambra1-wt (BPA+/+) melanomas.
2021-03-04 | GSE151134 | GEO
Project description:Environmental compounds are known to promote epigenetic transgenerational inheritance of adult onset disease in subsequent generations (F1M-bM-^@M-^SF3) following ancestral exposure during fetal gonadal sex determination. The current study was designed to determine if a mixture of plastic derived endocrine disruptor compounds bisphenol-A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and dibutyl phthalate (DBP) at two different doses promoted epigenetic transgenerational inheritance of adult onset disease and associated DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to either the M-bM-^@M-^\plasticsM-bM-^@M-^] or M-bM-^@M-^\lower dose plasticsM-bM-^@M-^] mixture during embryonic days 8 to 14 of gonadal sex determination and the incidence of adult onset disease was evaluated in F1 and F3 generation rats. There were significant increases in the incidence of total disease/abnormalities in F1 and F3 generation male and female animals from plastics lineages. Pubertal abnormalities, testis disease, obesity, and ovarian disease (primary ovarian insufficiency and polycystic ovaries) were increased in the F3 generation animals. Kidney and prostate disease were only observed in the direct fetally exposed F1 generation plastic lineage animals. Analysis of the plastics lineage F3 generation sperm epigenome previously identified 197 differential DNA methylation regions (DMR) in gene promoters, termed epimutations. A number of these transgenerational DMR form a unique direct connection gene network and have previously been shown to correlate with the pathologies identified. Observations demonstrate that a mixture of plastic derived compounds, BPA and phthalates, can promote epigenetic transgenerational inheritance of adult onset disease. The sperm DMR provide potential epigenetic biomarkers for transgenerational disease and/or ancestral environmental exposures. Methylated sperm DNA was isolated from rats ancestrally exposed to plastics (Bip). Three independent samples from the treatment group were obtained. Differential DNA methylation between treatment groups was determined using Nimblegen microarrays. Treated samples were paired with control samples and hybridized together on arrays (Bip1/Cip1, Bip2/Cip2, and Bip3/Cip3), resulting in three arrays for the treatment.
2014-07-22 | E-GEOD-59555 | biostudies-arrayexpress