Maternal Bisphenol A Exposure Impacts the Fetal Heart Transcriptome
Publication Date
February 25, 2014
Journal
PLOS ONE
Authors
Kalyan C. Chapalamadugu, Catherine A. Vande Voort, Matthew L. Settles, Barrie D. Robison, et al
Volume
9
Issue
2
Pages
e89096
DOI
https://dx.plos.org/10.1371/journal.pone.0089096
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0089096
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/24586524
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3934879
Europe PMC
http://europepmc.org/abstract/MED/24586524
Web of Science
000332385900027
Scopus
84897785769
Mendeley
http://www.mendeley.com/research/maternal-bisphenol-exposure-impacts-fetal-heart-transcriptome
Events
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Mendeley | Further Information

{"title"=>"Maternal bisphenol a exposure impacts the fetal heart transcriptome", "type"=>"journal", "authors"=>[{"first_name"=>"Kalyan C.", "last_name"=>"Chapalamadugu", "scopus_author_id"=>"23024350100"}, {"first_name"=>"Catherine A.", "last_name"=>"VandeVoort", "scopus_author_id"=>"7004716896"}, {"first_name"=>"Matthew L.", "last_name"=>"Settles", "scopus_author_id"=>"7004056075"}, {"first_name"=>"Barrie D.", "last_name"=>"Robison", "scopus_author_id"=>"7005610733"}, {"first_name"=>"Gordon K.", "last_name"=>"Murdoch", "scopus_author_id"=>"8549244900"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84897785769", "pui"=>"372599226", "doi"=>"10.1371/journal.pone.0089096", "isbn"=>"1932-6203", "sgr"=>"84897785769", "pmid"=>"24586524"}, "id"=>"156cd601-5061-32f5-a32f-654c1254a9dd", "abstract"=>"Conditions during fetal development influence health and disease in adulthood, especially during critical windows of organogenesis. Fetal exposure to the endocrine disrupting chemical, bisphenol A (BPA) affects the development of multiple organ systems in rodents and monkeys. However, effects of BPA exposure on cardiac development have not been assessed. With evidence that maternal BPA is transplacentally delivered to the developing fetus, it becomes imperative to examine the physiological consequences of gestational exposure during primate development. Herein, we evaluate the effects of daily, oral BPA exposure of pregnant rhesus monkeys (Macaca mulatta) on the fetal heart transcriptome. Pregnant monkeys were given daily oral doses (400 µg/kg body weight) of BPA during early (50-100 ± 2 days post conception, dpc) or late (100 ± 2 dpc--term), gestation. At the end of treatment, fetal heart tissues were collected and chamber specific transcriptome expression was assessed using genome-wide microarray. Quantitative real-time PCR was conducted on select genes and ventricular tissue glycogen content was quantified. Our results show that BPA exposure alters transcription of genes that are recognized for their role in cardiac pathophysiologies. Importantly, myosin heavy chain, cardiac isoform alpha (Myh6) was down-regulated in the left ventricle, and 'A Disintegrin and Metalloprotease 12', long isoform (Adam12-l) was up-regulated in both ventricles, and the right atrium of the heart in BPA exposed fetuses. BPA induced alteration of these genes supports the hypothesis that exposure to BPA during fetal development may impact cardiovascular fitness. Our results intensify concerns about the role of BPA in the genesis of human metabolic and cardiovascular diseases.", "link"=>"http://www.mendeley.com/research/maternal-bisphenol-exposure-impacts-fetal-heart-transcriptome", "reader_count"=>18, "reader_count_by_academic_status"=>{"Librarian"=>1, "Researcher"=>4, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>3, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>4}, "reader_count_by_user_role"=>{"Librarian"=>1, "Researcher"=>4, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>3, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>4}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Environmental Science"=>2, "Biochemistry, Genetics and Molecular Biology"=>4, "Medicine and Dentistry"=>4, "Agricultural and Biological Sciences"=>5, "Chemistry"=>1, "Psychology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Chemistry"=>{"Chemistry"=>1}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>1}, "Environmental Science"=>{"Environmental Science"=>2}}, "reader_count_by_country"=>{"South Korea"=>1, "Mexico"=>1, "France"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

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  • {"files"=>["https://ndownloader.figshare.com/files/1398140"], "description"=>"<p>Transcript levels of Thrb in the left ventricle (LV), right ventricle (RV), left atrium (LA) and the right atrium (RA) of rhesus monkey (Macaca mulatta) fetuses at birth. Fetuses were exposed maternally to a 400 µg/Kg. body weight of BPA dose (B) or 150 µL ethanol (C) during late gestation (LG, days 100±2–term). Data were analyzed by tissue and bars represent the mean ± S.E.M. of the log<sub>2</sub> (fold change). A two sample t-test was performed to identify significant BPA effects and a two-tailed p≤0.05 was considered statistically significant.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Physiogenomics", "Computational biology", "microarrays", "developmental biology", "embryology", "genomics", "Functional genomics", "Genome expression analysis", "toxicology", "Genetic toxicology", "Toxic agents", "Zoology", "Animal physiology", "cardiovascular", "pcr", "quantification", "thyroid", "receptor", "beta"], "article_id"=>944265, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Kalyan C. Chapalamadugu", "Catherine A. VandeVoort", "Matthew L. Settles", "Barrie D. Robison", "Gordon K. Murdoch"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0089096.g004", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Real_time_PCR_quantification_of_thyroid_hormone_receptor_beta_Thrb_expression_/944265", "title"=>"Real-time PCR quantification of thyroid hormone receptor beta (Thrb) expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-25 03:26:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/1398138"], "description"=>"<p>Real-time PCR quantification of myosin heavy chain 6, cardiac isoform alpha (Myh6) expression in the left ventricle (LV), right ventricle (RV), left atrium (LA) and the right atrium (RA) of rhesus monkey (Macaca mulatta) fetuses at birth. Fetuses were exposed maternally to a 400 µg/Kg. body weight of BPA dose (B) or 150 µL ethanol (C) during late gestation (LG, days 100±2–term). Data were analyzed by tissue and bars represent the mean ± S.E.M. of the log<sub>2</sub> (fold change). A two sample t-test was performed to identify significant BPA effects and a two-tailed p≤0.05 was considered statistically significant. Marginal significance between the groups was indicated with a ‘#’ symbol.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Physiogenomics", "Computational biology", "microarrays", "developmental biology", "embryology", "genomics", "Functional genomics", "Genome expression analysis", "toxicology", "Genetic toxicology", "Toxic agents", "Zoology", "Animal physiology", "cardiovascular", "myosin"], "article_id"=>944263, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Kalyan C. Chapalamadugu", "Catherine A. VandeVoort", "Matthew L. Settles", "Barrie D. Robison", "Gordon K. Murdoch"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0089096.g002", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Altered_fast_myosin_heavy_chain_expression_/944263", "title"=>"Altered fast myosin heavy chain expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-25 03:26:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/1398139"], "description"=>"<p>Real-time PCR quantification of the long isoform of A Disintegrin And Metalloprotease (Adam12-l) expression in the left ventricle (LV), right ventricle (RV), left atrium (LA) and the right atrium (RA) of rhesus monkey (Macaca mulatta) fetuses at birth. Fetuses were exposed maternally to a 400 µg/Kg. body weight of BPA dose (B) or 150 µL ethanol (C) during late gestation (LG, days 100±2–term). Data were analyzed by tissue and bars represent the mean ± S.E.M. of the log<sub>2</sub> (fold change). A two sample t-test was performed to identify significant BPA effects and a two-tailed p≤0.05 was considered statistically significant. Asterisk (*) indicate significantly different groups.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Physiogenomics", "Computational biology", "microarrays", "developmental biology", "embryology", "genomics", "Functional genomics", "Genome expression analysis", "toxicology", "Genetic toxicology", "Toxic agents", "Zoology", "Animal physiology", "cardiovascular", "adam12-l"], "article_id"=>944264, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Kalyan C. Chapalamadugu", "Catherine A. VandeVoort", "Matthew L. Settles", "Barrie D. Robison", "Gordon K. Murdoch"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0089096.g003", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_changes_in_Adam12_l_mRNA_/944264", "title"=>"Expression changes in Adam12-l mRNA.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-25 03:26:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/1398137"], "description"=>"<p>Whole transcriptome analysis was performed on the left ventricle (LV), right ventricle (RV), left atrium (LA) and the right atrium (RA) of rhesus monkey (Macaca mulatta) fetuses that were exposed maternally to a 400 µg/kg body weight, Bisphenol A (BPA), relative to matched control fetuses, either during, (A) early gestation, EG (days; 50–100±2) or, (B) late gestation, LG (days 100±2–term). Genes that changed by greater than ±1 log<sub>2</sub> fold change (1 LFC = 2 fold change) at an unadjusted p≤0.01 were considered significant and differentially expressed. Bars represent the number of upregulated (positive y-axis) or downregulated (negative y-axis) genes in each of the tissues.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Physiogenomics", "Computational biology", "microarrays", "developmental biology", "embryology", "genomics", "Functional genomics", "Genome expression analysis", "toxicology", "Genetic toxicology", "Toxic agents", "Zoology", "Animal physiology", "cardiovascular", "altered", "genes", "observed", "microarray", "transcriptome"], "article_id"=>944262, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Kalyan C. Chapalamadugu", "Catherine A. VandeVoort", "Matthew L. Settles", "Barrie D. Robison", "Gordon K. Murdoch"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0089096.g001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Total_number_of_significantly_altered_genes_observed_using_microarray_global_transcriptome_expression_analysis_/944262", "title"=>"Total number of significantly altered genes observed using microarray global transcriptome expression analysis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-25 03:26:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/1398148", "https://ndownloader.figshare.com/files/1398149", "https://ndownloader.figshare.com/files/1398150", "https://ndownloader.figshare.com/files/1398151", "https://ndownloader.figshare.com/files/1398152", "https://ndownloader.figshare.com/files/1398153", "https://ndownloader.figshare.com/files/1398154", "https://ndownloader.figshare.com/files/1398155"], "description"=>"<div><p>Conditions during fetal development influence health and disease in adulthood, especially during critical windows of organogenesis. Fetal exposure to the endocrine disrupting chemical, bisphenol A (BPA) affects the development of multiple organ systems in rodents and monkeys. However, effects of BPA exposure on cardiac development have not been assessed. With evidence that maternal BPA is transplacentally delivered to the developing fetus, it becomes imperative to examine the physiological consequences of gestational exposure during primate development. Herein, we evaluate the effects of daily, oral BPA exposure of pregnant rhesus monkeys (<i>Macaca mulatta</i>) on the fetal heart transcriptome. Pregnant monkeys were given daily oral doses (400 µg/kg body weight) of BPA during early (50–100±2 days post conception, dpc) or late (100±2 dpc – term), gestation. At the end of treatment, fetal heart tissues were collected and chamber specific transcriptome expression was assessed using genome-wide microarray. Quantitative real-time PCR was conducted on select genes and ventricular tissue glycogen content was quantified. Our results show that BPA exposure alters transcription of genes that are recognized for their role in cardiac pathophysiologies. Importantly, myosin heavy chain, cardiac isoform alpha (<i>Myh6</i>) was down-regulated in the left ventricle, and ‘A Disintegrin and Metalloprotease 12’, long isoform (<i>Adam12-l</i>) was up-regulated in both ventricles, and the right atrium of the heart in BPA exposed fetuses. BPA induced alteration of these genes supports the hypothesis that exposure to BPA during fetal development may impact cardiovascular fitness. Our results intensify concerns about the role of BPA in the genesis of human metabolic and cardiovascular diseases.</p></div>", "links"=>[], "tags"=>["Anatomy and physiology", "Physiogenomics", "Computational biology", "microarrays", "developmental biology", "embryology", "genomics", "Functional genomics", "Genome expression analysis", "toxicology", "Genetic toxicology", "Toxic agents", "Zoology", "Animal physiology", "cardiovascular", "bisphenol", "impacts", "fetal"], "article_id"=>944273, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Kalyan C. Chapalamadugu", "Catherine A. VandeVoort", "Matthew L. Settles", "Barrie D. Robison", "Gordon K. Murdoch"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0089096.s001", "https://dx.doi.org/10.1371/journal.pone.0089096.s002", "https://dx.doi.org/10.1371/journal.pone.0089096.s003", "https://dx.doi.org/10.1371/journal.pone.0089096.s004", "https://dx.doi.org/10.1371/journal.pone.0089096.s005", "https://dx.doi.org/10.1371/journal.pone.0089096.s006", "https://dx.doi.org/10.1371/journal.pone.0089096.s007", "https://dx.doi.org/10.1371/journal.pone.0089096.s008"], "stats"=>{"downloads"=>50, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Maternal_Bisphenol_A_Exposure_Impacts_the_Fetal_Heart_Transcriptome_/944273", "title"=>"Maternal Bisphenol A Exposure Impacts the Fetal Heart Transcriptome", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-02-25 03:26:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/1398146"], "description"=>"<p>ND - below differential expression filter criteria.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Physiogenomics", "Computational biology", "microarrays", "developmental biology", "embryology", "genomics", "Functional genomics", "Genome expression analysis", "toxicology", "Genetic toxicology", "Toxic agents", "Zoology", "Animal physiology", "cardiovascular", "genes", "observed", "microarray", "rhesus", "fetal", "exposed", "maternally", "bpa", "lg"], "article_id"=>944271, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Kalyan C. Chapalamadugu", "Catherine A. VandeVoort", "Matthew L. Settles", "Barrie D. Robison", "Gordon K. Murdoch"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0089096.t003", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Differentially_expressed_genes_observed_using_microarray_on_rhesus_fetal_heart_exposed_maternally_to_BPA_or_vehicle_during_early_gestation_LG_days_100_177_2_8211_term_/944271", "title"=>"Differentially expressed genes observed using microarray on rhesus fetal heart exposed maternally to BPA or vehicle during early gestation, LG (days; 100±2–term).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-02-25 03:26:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/1398147"], "description"=>"<p>Sequences of primers; forward (FP), reverse (RP), Taqman probe (TP) specific to gene transcripts analyzed.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Physiogenomics", "Computational biology", "microarrays", "developmental biology", "embryology", "genomics", "Functional genomics", "Genome expression analysis", "toxicology", "Genetic toxicology", "Toxic agents", "Zoology", "Animal physiology", "cardiovascular", "mgb", "primer", "probe"], "article_id"=>944272, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Kalyan C. Chapalamadugu", "Catherine A. VandeVoort", "Matthew L. Settles", "Barrie D. Robison", "Gordon K. Murdoch"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0089096.t001", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Taqman_MGB_primer_amp_probe_system_/944272", "title"=>"Taqman MGB primer & probe system.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-02-25 03:26:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/1398142"], "description"=>"<p>Real-time PCR quantification of Pdk4 gene was performed on the left ventricle (LV), right ventricle (RV), left atrium (LA) and the right atrium (RA) samples of rhesus monkey (Macaca mulatta) fetuses at birth. Fetuses were exposed maternally to a 400 µg/Kg. body weight of BPA dose (B) or 150 µL ethanol (C) during late gestation (LG, days 100±2–term). Data were analyzed by tissue and bars represent the mean ± S.E.M. of the log<sub>2</sub> (fold change). A two sample t-test was performed to identify significant BPA effects and a two-tailed p≤0.05 was considered statistically significant.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Physiogenomics", "Computational biology", "microarrays", "developmental biology", "embryology", "genomics", "Functional genomics", "Genome expression analysis", "toxicology", "Genetic toxicology", "Toxic agents", "Zoology", "Animal physiology", "cardiovascular", "dehydrogenase", "kinase", "isozyme", "mrna"], "article_id"=>944267, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Kalyan C. Chapalamadugu", "Catherine A. VandeVoort", "Matthew L. Settles", "Barrie D. Robison", "Gordon K. Murdoch"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0089096.g006", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pyruvate_dehydrogenase_kinase_isozyme_4_Pdk4_mRNA_expression_/944267", "title"=>"Pyruvate dehydrogenase kinase isozyme 4 (Pdk4) mRNA expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-25 03:26:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/1398141"], "description"=>"<p>Expression of Gyg1 mRNA in the left ventricle (LV), right ventricle (RV), left atrium (LA) and the right atrium (RA) of rhesus monkey (Macaca mulatta) fetuses at birth was measured. Fetuses were exposed maternally to a 400 µg/Kg. body weight of BPA dose (B) or 150 µL ethanol (C) during late gestation (LG, days 100±2–term). Data were analyzed by tissue and bars represent the mean ± S.E.M. of the log<sub>2</sub> (fold change). A two sample t-test was performed to identify significant BPA effects and a two-tailed p≤0.05 was considered statistically significant.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Physiogenomics", "Computational biology", "microarrays", "developmental biology", "embryology", "genomics", "Functional genomics", "Genome expression analysis", "toxicology", "Genetic toxicology", "Toxic agents", "Zoology", "Animal physiology", "cardiovascular", "pcr", "quantification", "glycogenin"], "article_id"=>944266, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Kalyan C. Chapalamadugu", "Catherine A. VandeVoort", "Matthew L. Settles", "Barrie D. Robison", "Gordon K. Murdoch"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0089096.g005", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Real_time_PCR_quantification_of_glycogenin_Gyg1_expression_/944266", "title"=>"Real-time PCR quantification of glycogenin (Gyg1) expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-25 03:26:01"}

PMC Usage Stats | Further Information

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Relative Metric

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