53 Pre-implantation exposure to bisphenol A and 4-tert-octylphenol result in disruption of calcium channels

2019 ◽  
Vol 31 (1) ◽  
pp. 152
Author(s):  
D. N. Tran ◽  
J.-H. Lee ◽  
Y.-M. Yoo ◽  
E.-M. Jung ◽  
C. Ahn ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bisphenol A ◽  
Calcium Transport ◽  
Oestrogen Receptor ◽  
Implantation Site ◽  
Vehicle Group ◽  
Mrna Levels ◽  
Implantation Failure ◽  
Transport Channel ◽  
Altered Expression

Miscarriage due to blastocyst implantation failure occurs in up to two-thirds of all miscarriage cases in humans. Calcium (Ca2+) has been shown to involve many cellular signal transduction pathways as well as regulation of cell adhesion, which is necessary for the physiology process of endometrial epithelial cell transformation and stromal cell decidualization during embryo implantation. Exposure to endocrine-disrupting chemicals (ED) can regulate the expression of genes associated with calcium transport in during pregnancy such as TRPV5, TRPV6, PMCA, and NCX1. Additionally, exposure to ED during early gestation results in disrupted intrauterine implantation, uterine receptive, leading to implantation failure. In this study, oestrogen (E2), bisphenol A (BPA), octylphenol (OP), and/or ICI 182,780 (oestrogen receptor antagonist, ICI) were injected subcutaneously from gestation Day 1 to gestation Day 3 post coitus. The number of implantation sites was significantly lower in the OP group, and no implantation site was observed in the E2 and ED+ICI groups. There were differences in the expression of calcium transient transport channel between maternal uterine and implantation. The level of TRPV6 and TRPV5 mRNA and protein was significantly increased by ED and/or ICI treatment in the uterus. The levels of TRPV5 and TRPV6 gene expression were significantly increased by ED with/without ICI treatment in the uterus. However, TRPV5 and TRPV6 gene expression was significantly lower in implantation site samples. The NCX1 and PMCA1 mRNA levels were significantly decreased by OP and BPA in the implantation site samples. Both mRNA and protein levels of MUC1 were markedly higher in all groups, except the BPA group when compared with the vehicle group in the uterus. The LIF and HOXA-10 mRNA were significantly low in E2; BPA+ICI; OP; and/or ICI in both the uterus and implantation site. Expression of the oestrogen receptor (ERa) and progesterone receptor (PR) was significantly lower in all groups except the BPA group when compared with the vehicle group. Taken together, E2, BPA, and OP disrupt the success of implantation through altered expression of calcium transport genes.

scholarly journals Effects of Bisphenol A and 4-Tert-octylphenol on Embryo Implantation Failure in Mouse

2018 ◽  
Author(s):  
Dinh Nam Tran ◽  
Eui-Man Jung ◽  
Changhwan Ahn ◽  
Jae-Hwan Lee ◽  
Yeong-Min Yoo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bisphenol A ◽  
Calcium Transport ◽  
Embryo Implantation ◽  
Implantation Site ◽  
Mrna Levels ◽  
Implantation Failure ◽  
Gene Expressions ◽  
Expression Levels ◽  
Implantation Sites

Miscarriage due to blastocyst implantation failure occurs in up to two-thirds of all miscarriage cases in human. The calcium ion has been shown to be involved in many cellular signal transduction pathways as well as in the regulation of cell adhesion, which is necessary for the embryo implantation process. Exposure to endocrine-disrupting chemicals (EDs) during early gestation results in disruption of intrauterine implantation and uterine reception, leading to implantation failure. In this study, ovarian estrogen (E2), bisphenol A (BPA), or 4-tert-octylphenol (OP), with or without ICI 182,780 (ICI) were injected subcutaneously from gestation day 1 to gestation day 3 post-coitus. The expression levels of the calcium transport genes were assessed in maternal uteri and implantation sites. The number of implantation sites was significantly low in the OP group, and implantation sites were absent in the E2 and EDs+ICI groups. There were different calcium transient transport channel expression levels in uterus and implantation site samples. The levels of TRPV5 and TRPV6 gene expression were significantly increased by EDs with/without ICI treatment in uterus. Whereas, TRPV5 and TRPV6 gene expression were significantly lower in implantation sites samples. NCX1 and PMCA1 mRNA levels were significantly decreased by OP and BPA in the implantation site samples. Compared to vehicle treatment in uterus, both the MUC1 mRNA and protein levels were markedly high in all but the BPA group. Taken together, these results suggest that both BPA and OP can impair embryo implantation through alteration of calcium transport gene expressions and by affecting uterine receptivity.

scholarly journals Effects of Bisphenol A and 4-tert-Octylphenol on Embryo Implantation Failure in Mouse

2018 ◽  
Vol 15 (8) ◽  
pp. 1614 ◽  
Author(s):  
Dinh Nam Tran ◽  
Eui-Man Jung ◽  
Changhwan Ahn ◽  
Jae-Hwan Lee ◽  
Yeong-Min Yoo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bisphenol A ◽  
Calcium Transport ◽  
Embryo Implantation ◽  
Implantation Site ◽  
Mrna Levels ◽  
Implantation Failure ◽  
Gene Expressions ◽  
Expression Levels ◽  
Implantation Sites

Miscarriage due to blastocyst implantation failure occurs in up to two-thirds of all human miscarriage cases. Calcium ion has been shown to be involved in many cellular signal transduction pathways as well as in the regulation of cell adhesion, which is necessary for the embryo implantation process. Exposure to endocrine-disrupting chemicals (EDs) during early gestation results in disruption of intrauterine implantation and uterine reception, leading to implantation failure. In this study, ovarian estrogen (E2), bisphenol A (BPA), or 4-tert-octylphenol (OP), with or without ICI 182,780 (ICI) were injected subcutaneously from gestation day 1 to gestation day 3 post-coitus. The expression levels of the calcium transport genes were assessed in maternal uteri and implantation sites. The number of implantation sites was significantly low in the OP group, and implantation sites were absent in the E2, ICI and EDs + ICI groups. There were different calcium transient transport channel expression levels in uterus and implantation site samples. The levels of TRPV5 and TRPV6 gene expression were significantly increased by EDs with/without ICI treatment in utero. Meanwhile, TRPV5 and TRPV6 gene expression were significantly lower in implantation sites samples. NCX1 and PMCA1 mRNA levels were significantly decreased by OP and BPA in the implantation site samples. Compared to vehicle treatment in the uterus, both the MUC1 mRNA and protein levels were markedly high in all but the BPA group. Taken together, these results suggest that both BPA and OP can impair embryo implantation through alteration of calcium transport gene expressions and by affecting uterine receptivity.

scholarly journals In utero Bisphenol A Exposure Is Linked with Sex Specific Changes in the Transcriptome and Methylome of Human Amniocytes

2019 ◽  
Vol 105 (2) ◽  
pp. 453-467
Author(s):  
Amita Bansal ◽  
Nicole Robles-Matos ◽  
Paul Zhiping Wang ◽  
David E Condon ◽  
Apoorva Joshi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Bisphenol A ◽  
Gestational Age ◽  
Molecular Mechanisms ◽  
In Utero ◽  
Metabolic Dysfunction ◽  
Altered Expression ◽  
Obesity And Diabetes ◽  
Genome Wide

Abstract Context Prenatal exposure to bisphenol A (BPA) is linked to obesity and diabetes but the molecular mechanisms driving these phenomena are not known. Alterations in deoxyribonucleic acid (DNA) methylation in amniocytes exposed to BPA in utero represent a potential mechanism leading to metabolic dysfunction later in life. Objective To profile changes in genome-wide DNA methylation and expression in second trimester human amniocytes exposed to BPA in utero. Design A nested case-control study was performed in amniocytes matched for offspring sex, maternal race/ethnicity, maternal age, gestational age at amniocentesis, and gestational age at birth. Cases had amniotic fluid BPA measuring 0.251 to 23.74 ng/mL. Sex-specific genome-wide DNA methylation analysis and RNA-sequencing (RNA-seq) were performed to determine differentially methylated regions (DMRs) and gene expression changes associated with BPA exposure. Ingenuity pathway analysis was performed to identify biologically relevant pathways enriched after BPA exposure. In silico Hi-C analysis identified potential chromatin interactions with DMRs. Results There were 101 genes with altered expression in male amniocytes exposed to BPA (q < 0.05) in utero, with enrichment of pathways critical to hepatic dysfunction, collagen signaling and adipogenesis. Thirty-six DMRs were identified in male BPA-exposed amniocytes and 14 in female amniocyte analysis (q < 0.05). Hi-C analysis identified interactions between DMRs and 24 genes with expression changes in male amniocytes and 12 in female amniocytes (P < 0.05). Conclusion In a unique repository of human amniocytes exposed to BPA in utero, sex-specific analyses identified gene expression changes in pathways associated with metabolic disease and novel DMRs with potential distal regulatory functions.

scholarly journals <i>In Vitro</i> Exposure to Isoprene-Derived Secondary Organic Aerosol by Direct Deposition and its Effects on <i>COX-2</i> and <i>IL-8</i> Gene Expression

2016 ◽  
Author(s):  
Maiko Arashiro ◽  
Ying-Hsuan Lin ◽  
Kenneth G. Sexton ◽  
Zhenfa Zhang ◽  
Ilona Jaspers ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Secondary Organic Aerosol ◽  
Organic Aerosol ◽  
Mrna Levels ◽  
Altered Expression ◽  
Direct Deposition ◽  
Discovery Research ◽  
Human Lung Cells ◽  
Cox 2

Abstract. Atmospheric oxidation of isoprene, the most abundant non-methane hydrocarbon emitted into Earth’s atmosphere primarily from terrestrial vegetation, is now recognized as a major contributor to the global secondary organic aerosol (SOA) burden. Anthropogenic pollutants significantly enhance isoprene SOA formation through acid-catalyzed heterogeneous chemistry of epoxide products. Since isoprene SOA formation as a source of fine aerosol is a relatively recent discovery, research is lacking on evaluating its potential adverse effects on human health. The objective of this study was to examine the effect of isoprene-derived SOA on inflammation-associated gene expression in human lung cells using a direct deposition exposure method. We assessed altered expression of inflammation-related genes in human bronchial epithelial cells (BEAS-2B) exposed to isoprene-derived SOA generated in an outdoor chamber facility. Measurements of gene expression of known inflammatory biomarkers interleukin 8 (IL-8) and cyclooxygenase 2 (COX-2) in exposed cells, together with complementary chemical measurements, showed that a dose of 0.067 µg cm−2 of SOA from isoprene photooxidation leads to statistically significant increases in IL-8 and COX-2 mRNA levels. Resuspension exposures using aerosol filter extracts corroborated these findings, supporting the conclusion that isoprene-derived SOA constituents induce the observed changes in mRNA levels. Future studies are needed to systematically examine the molecular mechanisms of toxicity.

scholarly journals A Unique Pattern of Bisphenol A Effects on Nerve Growth Factor Gene Expression in Embryonic Mouse Hypothalamic Cell Line N-44

2014 ◽  
Vol 65 (3) ◽  
pp. 293-299 ◽  
Author(s):  
Katsuhiko Warita ◽  
Tomoko Mitsuhashi ◽  
Nobuhiko Hoshi ◽  
Ken-ichi Ohta ◽  
Shingo Suzuki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Bisphenol A ◽  
Cell Line ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Embryonic Mouse ◽  
Nerve Growth ◽  
Unique Pattern

AbstractWe investigated the toxicity of bisphenol A (BPA) by determining the gene expression of nerve growth factor (Ngf in the embryonic mouse cell line mHypoE-N44 derived from the hypothalamus exposed to BPA dose range between 0.02 and 200 μmol L-1 for 3 h. Ngf mRNA levels decreased in a dose-dependent manner, with significant reductions observed in the 2 to 50 μmol L-1 BPA treatment groups compared to controls. However, at 100 to 200 μmol L-1 the NgfmRNA gradually increased and was significantly higher than control, while the expression of the apoptosis-related genes Caspase 3 and transformation-related protein 73 decreased significantly. These results suggest that in an embryonic hypothalamic cell line the higher doses of BPA induce a unique pattern of Ngf gene expression and that BPA has the potential to suppress apoptosis essential for early-stage brain development.

scholarly journals Genetics of trans-regulatory variation in gene expression

2017 ◽  
Author(s):  
Frank W. Albert ◽  
Joshua S. Bloom ◽  
Jake Siegel ◽  
Laura Day ◽  
Leonid Kruglyak
Keyword(s):  
Gene Expression ◽  
Statistical Power ◽  
Target Genes ◽  
Transcriptome Profiling ◽  
Mrna Levels ◽  
Heritable Variation ◽  
Altered Expression ◽  
Regulatory Variation ◽  
Transcription Factor Genes ◽  
Transcriptome Variation

AbstractHeritable variation in gene expression provides a critical bridge between differences in genome sequence and the biology of many traits, including common human diseases. However, the sources of most regulatory genetic variation remain unknown. Here, we used transcriptome profiling in 1,012 yeast segregants to map the genetic basis of variation in gene expression with high statistical power. We identified expression quantitative trait loci (eQTL) that together account for over 70% of the total genetic contribution to variation in mRNA levels, allowing us to examine the sources of regulatory variation comprehensively. We found that variation in the expression of a typical gene has a complex genetic architecture involving multiple eQTL. We also detected hundreds of eQTL pairs with significant non-additive interactions in an unbiased genome-wide scan. Although most genes were influenced by a local eQTL located close to the gene, most expression variation arose from distant, trans-acting eQTL located far from their target genes. Nearly all distant eQTL clustered at 102 “hotspot” locations, some of which influenced the expression of thousands of genes. Hotspot regions were enriched for transcription factor genes and altered expression of their target genes though both direct and indirect mechanisms. Many local eQTL had no detectable effects on the expression of other genes in trans. These results reveal the complexity of genetic influences on transcriptome variation in unprecedented depth and detail.

152 BISPHENOL A AND 17-BETA-OESTRADIOL RESULTED IN THE GENE ALTERATIONS IN OESTROGEN-RECEPTOR POSITIVE BG-1 OVARIAN CANCER CELLS

2012 ◽  
Vol 24 (1) ◽  
pp. 188
Author(s):  
K.-A Hwang ◽  
S.-H. Hyun ◽  
E.-B. Jeung ◽  
K.-C. Choi
Keyword(s):  
Ovarian Cancer ◽  
Bisphenol A ◽  
Cancer Cells ◽  
Oestrogen Receptor ◽  
Endocrine Disrupting Chemicals ◽  
Ovarian Cancer Cells ◽  
Mrna Levels ◽  
Endocrine Disrupting ◽  
Er Positive ◽  
Gene Alterations

Because endocrine disrupting chemicals may interfere with the endocrine systems of our body and have an oestrogenic activity, we evaluated the effects of bisphenol A (BPA) on the transcriptional levels of altered genes in oestrogen receptor (ER)-positive BG-1 ovarian cancer cells. A microarray and RT-qPCR were employed to detect gene alterations in these cells following treatments. In this study, treatment with 17-β-oestradiol (E2) or BPA increased mRNA levels of E2-responsive genes related to apoptosis, cancer and cell cycle, signal transduction and nucleic acid binding and so on. Parallel with the microarray data, the mRNA levels of some altered genes including RAB31_member RAS oncogene family (U59877), cyclin D1 (X59798), cyclin-dependent kinase 4 (U37022), IGF-binding protein 4 (U20982) and anti-mullerian hormone (NM_000479) were significantly induced by E2 or BPA in this cell model. These results indicate that BPA in parallel with E2 induced the transcriptional levels of E2-responsive genes in an ER-positive BG-1 cells. In conclusion, these microarray and RT-qPCR results indicate that BPA, a potential weak oestrogen, may have an oestrogenic effect by regulating E2-responsive genes in ER-positive BG-1 cells and that BG-1 cells would be the best in vitro model to detect these oestrogenic endocrine disrupting chemicals. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2011-0015385).

Abstract 438: Global Gene Expression Analysis of Human Perivascular Adipocytes Reveals Reduced Expression of Insulin and Wnt Signaling Genes: Implications for Inflammatory Crosstalk

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Tapan K Chatterjee ◽  
David G Kuhel ◽  
David Y Hui ◽  
Neal L Weintraub
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Human Subjects ◽  
Adipogenic Differentiation ◽  
Expression Patterns ◽  
Mrna Levels ◽  
Altered Expression

Inflammatory crosstalk between PV adipose tissue and the blood vessel wall has been proposed to contribute to the pathogenesis of atherosclerosis. We reported that PV adipocytes exhibit a pro-inflammatory phenotype, reduced state of differentiation, and altered expression of developmental genes as compared with subcutaneous (SQ) adipocytes derived from the same human subjects. To define global differences in gene expression patterns between PV and SQ adipocytes, genome-wide microarray studies were performed in three sets of in vitro differentiated SQ and PV adipocytes derived from unrelated human subjects. Insulin-regulated and Wnt signaling genes were markedly down-regulated in PV adipocytes. Validation of microarray data by qPCR demonstrated reductions in expression of C/EBPα, PPARγ, FABP4, adiponectin, lipoprotein lipase, hormone sensitive lipase and perilipin in PV compared to SQ adipocytes. We further observed that insulin-induced Akt ser-473 phosphorylation and glucose uptake were markedly reduced (∼ 3 fold and 4 fold, respectively) in differentiated PV adipocytes compared to SQ adipocytes. The mRNA levels of insulin and insulin-like growth factor receptors, however, were similar in adipocytes differentiated from these two depots. Regarding the Wnt pathway, PV adipocytes exhibited dramatically elevated expression of Wnt inhibitor DKK1 (2864%) and reduced expression of Wnt 5A (50%), FDZ4 (38%), and LRP5 (38%). Further evaluation revealed that these Wnt signaling pathway genes, like those of the insulin signaling pathway, correlated with the extent of adipogenic differentiation. We propose that dysregulation of Wnt 5A/FDZ4 and insulin signaling pathways contributes to impaired adipogenic differentiation and insulin resistance in PV adipocytes. This, in turn, may contribute to heightened inflammatory crosstalk between PV adipose tissue and the vascular wall in the setting of atherosclerosis.

scholarly journals In vitro exposure to isoprene-derived secondary organic aerosol by direct deposition and its effects on <i>COX-2</i> and <i>IL-8</i> gene expression

2016 ◽  
Vol 16 (22) ◽  
pp. 14079-14090 ◽  
Author(s):  
Maiko Arashiro ◽  
Ying-Hsuan Lin ◽  
Kenneth G. Sexton ◽  
Zhenfa Zhang ◽  
Ilona Jaspers ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Lung ◽  
Secondary Organic Aerosol ◽  
Organic Aerosol ◽  
Lung Cells ◽  
Mrna Levels ◽  
Altered Expression ◽  
Direct Deposition ◽  
Human Lung Cells ◽  
Cox 2

Abstract. Atmospheric oxidation of isoprene, the most abundant non-methane hydrocarbon emitted into Earth's atmosphere primarily from terrestrial vegetation, is now recognized as a major contributor to the global secondary organic aerosol (SOA) burden. Anthropogenic pollutants significantly enhance isoprene SOA formation through acid-catalyzed heterogeneous chemistry of epoxide products. Since isoprene SOA formation as a source of fine aerosol is a relatively recent discovery, research is lacking on evaluating its potential adverse effects on human health. The objective of this study was to examine the effect of isoprene-derived SOA on inflammation-associated gene expression in human lung cells using a direct deposition exposure method. We assessed altered expression of inflammation-related genes in human bronchial epithelial cells (BEAS-2B) exposed to isoprene-derived SOA generated in an outdoor chamber facility. Measurements of gene expression of known inflammatory biomarkers interleukin 8 (IL-8) and cyclooxygenase 2 (COX-2) in exposed cells, together with complementary chemical measurements, showed that a dose of 0.067 µg cm−2 of SOA from isoprene photooxidation leads to statistically significant increases in IL-8 and COX-2 mRNA levels. Resuspension exposures using aerosol filter extracts corroborated these findings, supporting the conclusion that isoprene-derived SOA constituents induce the observed changes in mRNA levels. The present study is an attempt to examine the early biological responses of isoprene SOA exposure in human lung cells.

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