Transcriptomics analysis of bisphenol A induced injury on human normal ovarian epithelial cells at human-relevant levels
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE185112 | GEO | 2022/04/21
REPOSITORIES: GEO
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Project description:Background: Animal-based studies indicate that Bisphenol A (BPA) exposure is detrimental to reproductive health, but its impact on the earliest stages of germ cell development remain poorly defined. Objective: Using a murine in vitro model of early germ cell specification and differentiation, we sought to assess whether exposure to low levels of BPA prior to Primordial Germ Cell (PGC) formation alters their differentiation trajectory and unique molecular program. Methods: We used an established method of in vitro differentiation of mouse Embryonic Stem Cells (ESCs) into Epiblast-like Cells (EpiLCs) followed by PGC-Like Cells (PGCLCs) which together recapitulates defined stages of early germ cell development. Cellular consequences were determined using hemocytometer-based cell counting, fixation and intracellular staining followed by flow cytometry/FACS on cells exposed to increasing doses of BPA. We also generated RNA-seq libraries from RNA extracted from FACS-purified PGCLCs and performed transcriptome analysis using bioinformatics-based approaches, to interrogate and characterise gene expression changes resulting from BPA exposure. Results: Exposure of EpiLCs to BPA resulted in a dose-dependent increase in cell number, associated with an increase proportion of cells in S-phase as well as a reduced proportion undergoing apoptosis. Exposure also resulted in a greater proportion of EpiLCs showing signs of DNA damage. Remarkably, EpiLC exposure did not negatively impact PGC specification and resulted in dose-dependent increase in PGCLC proliferation. However, PGCLC transcriptome analysis revealed an aberrant program with significant deregulation of X-linked genes and retrotransposon expression. Differential gene expression analysis also revealed the deregulation of genes associated with lipid metabolism as well as deregulated expression of genes associated with later stages of gametogenesis. Conclusions: Our findings represent the first characterisation of the consequences of early BPA exposure on a model of PGC development, highlighting altered cell behaviour and underlying pathways and molecular processes.
2021-09-01 | GSE157570 | GEO
Project description:Background: Exposure to the endocrine-disrupting chemical bisphenol A (BPA) is correlated with obesity and promotes adipogenesis of human preadipocytes into mature adipocytes. However, the mechanism of action of BPA-induced human adipogenesis in vitro remains to be fully characterized. Methods: In this study, potential mechanisms of BPA-induced adipogenesis in primary human preadipocytes were evaluated using gene expression microarray analysis. Preadipocytes from donors with normal body mass indexes were differentiated in the presence of 50 µM BPA or 1 µM dexamethasone (DEX) for 48 hours. Results: Microarray analysis revealed 235 up-regulated and 138 down-regulated genes following BPA treatment, including sterol regulatory element binding factor 1 (SREBF1), a key transcription factor known to regulate many components of lipid metabolism and adipogenesis. For DEX treated preadipocytes, 1136 genes were up-regulated, including the adipogenic marker lipoprotein lipase, while 1031 genes were down-regulated. Ingenuity Pathway Analysis was used to identify functional annotations of the gene expression changes associated with response to BPA and DEX treatments. BPA exposure was associated with expression changes in the genes involved in the accumulation of triacylglycerol while DEX was linked to metabolism of triacylglycerol and cleavage of fatty acids. The analysis also revealed enrichment of genes in pathways known to be associated with BPA exposure including thyroid-receptor/retinoic X receptor (TR/RXR) activation, mammalian target of rapamycin (mTOR) signaling and cholesterol biosynthesis, whereas DEX treatment was linked to cholesterol biosynthesis and ethanol degradation. Interestingly, alterations in the mTOR pathway in response to BPA did not occur in DEX-treated preadipocytes. Conclusions: Our data suggest that potential mechanisms of action of BPA-induced adipogenesis involve SREBF1, the TR/RXR and the mTOR pathways.
2014-04-15 | GSE56085 | GEO
Project description:Background: Exposure to the endocrine-disrupting chemical bisphenol A (BPA) is correlated with obesity and promotes adipogenesis of human preadipocytes into mature adipocytes. However, the mechanism of action of BPA-induced human adipogenesis in vitro remains to be fully characterized. Methods: In this study, potential mechanisms of BPA-induced adipogenesis in primary human preadipocytes were evaluated using gene expression microarray analysis. Preadipocytes from donors with normal body mass indexes were differentiated in the presence of 50 M-BM-5M BPA or 1 M-BM-5M dexamethasone (DEX) for 48 hours. Results: Microarray analysis revealed 235 up-regulated and 138 down-regulated genes following BPA treatment, including sterol regulatory element binding factor 1 (SREBF1), a key transcription factor known to regulate many components of lipid metabolism and adipogenesis. For DEX treated preadipocytes, 1136 genes were up-regulated, including the adipogenic marker lipoprotein lipase, while 1031 genes were down-regulated. Ingenuity Pathway Analysis was used to identify functional annotations of the gene expression changes associated with response to BPA and DEX treatments. BPA exposure was associated with expression changes in the genes involved in the accumulation of triacylglycerol while DEX was linked to metabolism of triacylglycerol and cleavage of fatty acids. The analysis also revealed enrichment of genes in pathways known to be associated with BPA exposure including thyroid-receptor/retinoic X receptor (TR/RXR) activation, mammalian target of rapamycin (mTOR) signaling and cholesterol biosynthesis, whereas DEX treatment was linked to cholesterol biosynthesis and ethanol degradation. Interestingly, alterations in the mTOR pathway in response to BPA did not occur in DEX-treated preadipocytes. Conclusions: Our data suggest that potential mechanisms of action of BPA-induced adipogenesis involve SREBF1, the TR/RXR and the mTOR pathways. The study used 40 samples in total which included 5 replicates (cells from 5 unique donors) of 8 different treatments. The 8 treatments were as follows: 1) untreated (negative) control for 48 hours, 2) 25 uM BPA treated for 48 hours, 3) 50 uM BPA treated for 48 hours, 4) untreated (negative) control + insulin for 48 hours, 5) 25 uM BPA + insulin treated for 48 hours, 6) 50 uM BPA + insulin treated for 48 hours, 7) 1uM Dexamethasone + insulin treated for 48 hours, 8) 1uM Dexamethasone + insulin treated for 96 hours.
2014-04-15 | E-GEOD-56085 | biostudies-arrayexpress
Project description:The widely used chemical bisphenol A (BPA) has been associated with several health effects. In recent years, many derivatives were developed to replace BPA without thorough toxicological evaluation. Here, we employed a human embryoid body (EB)-based in vitro global differentiation and hepatic specification models, followed by RNA-seq analyses, to comprehensively study the potential developmental toxicity of six BPA replacements (BPS, BPF, BPZ, BPB, BPE, and BPAF), as compared to BPA. We found that bisphenols may disrupt lineage commitment and lipid metabolism during early embryonic development. These effects mostly manifested via the dysregulation of HOX and APO family genes. Moreover, among the seven bisphenols analyzed, BPE, due to lower potential developmental toxicity, stood out as a relatively safe substitute of BPA in many applications, especially for infant/baby products.
2020-10-27 | GSE149753 | GEO
Project description:The endocrine disrupting chemical bisphenol A (BPA) can affect reproductive organs, tissues and cells in several species. Treatment of human endometrial endothelial cells (HEECs) with 50 µM BPA decreased their proliferation compared with the control. Microarray analyses revealed that BPA affected biological processes such as the cell cycle, cell division, and cytoskeleton organization, confirming the results of the proliferation assay. Expression of three of the most differentially expressed genes identified in the microarray analysis was verified by real-time quantitative reverse transcription polymerase chain reaction in five HEEC cultures obtained from women in the proliferative phase and in five cultures obtained from women in the secretory phase of the menstrual cycle after treatment with BPA. The present study supports our previous findings of decreased proliferation and increased cell death in response to BPA, and may offer important clues to the mechanisms of action of BPA. Keywords: Exposure analysis
2008-03-13 | GSE10802 | GEO
Project description:The endocrine disrupting chemical bisphenol A (BPA) can affect reproductive organs, tissues and cells in several species. Treatment of human endometrial endothelial cells (HEECs) with 50 µM BPA decreased their proliferation compared with the control. Microarray analyses revealed that BPA affected biological processes such as the cell cycle, cell division, and cytoskeleton organization, confirming the results of the proliferation assay. Expression of three of the most differentially expressed genes identified in the microarray analysis was verified by real-time quantitative reverse transcription polymerase chain reaction in five HEEC cultures obtained from women in the proliferative phase and in five cultures obtained from women in the secretory phase of the menstrual cycle after treatment with BPA. The present study supports our previous findings of decreased proliferation and increased cell death in response to BPA, and may offer important clues to the mechanisms of action of BPA. Keywords: Exposure analysis Two-condition experiments, BPA-exposed vs. control HEEC. Biological replicates: 5 HEEC cultures, independently grown, exposed and harvested. One replicate per array. Dye-swaps for exposed and reference samples between replicates.
2010-05-25 | E-GEOD-10802 | biostudies-arrayexpress
Project description:Purpose: finding differential transcripts usage in environmentally harzardous chemical, bisphenol A (BPA) in human retinal cells Methods: transcriptome analysis by the RNA-seq via mRNA pull-down Results: We found that BPA increases cellular toxicity by the increasing of early apoptotic pathway in Y79 cells. Also, over thounds of retained intron events were detected from the RNA-seq analysis. Conclusions: Bisphenol A (BPA) increases early cytotoxic effects in Y79 cells through the early apoptotic pathway and changes the context of trascript through the splicing regulation mechanisms.
2021-02-16 | GSE146255 | 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:In this study we used RNA-seq to characterize the dose-response for global transcriptomic alterations induced by BPA, BPF, BPS and TBBA in H9 (WA09) human embryonic stem (hES) cells. To assess the relative biological activity and potency of BPA and structural analogs BPS, BPF and TBBP, we examined the stem cell transcriptome in H9 hES cells following exposure to these chemicals at concentrations that covered greater than three orders of magnitude (1 microM to >100 microM). These exposure levels are considered to be near human relevant and range from noncytotoxic to overtly toxic. Overall, this study provides basic mechanistic information about the effects of BPA and structural analogs BPS, BPF and TBBP on the transcriptome of hES cells and demonstrates how these data can be applied to derive benchmark dose modeling (BMD) information useful for comparing relative potencies of these structurally related chemicals.
2021-07-19 | GSE153320 | GEO
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.
2020-05-22 | GSE140640 | GEO