Environmentally Induced Epigenetic Transgenerational Inheritance of Altered Sertoli Cell Transcriptome and Epigenome: Molecular Etiology of Male Infertility
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{"title"=>"Environmentally Induced Epigenetic Transgenerational Inheritance of Altered Sertoli Cell Transcriptome and Epigenome: Molecular Etiology of Male Infertility", "type"=>"journal", "authors"=>[{"first_name"=>"Carlos", "last_name"=>"Guerrero-Bosagna", "scopus_author_id"=>"8605905700"}, {"first_name"=>"Marina", "last_name"=>"Savenkova", "scopus_author_id"=>"56629497000"}, {"first_name"=>"Md Muksitul", "last_name"=>"Haque", "scopus_author_id"=>"55038823600"}, {"first_name"=>"Eric", "last_name"=>"Nilsson", "scopus_author_id"=>"7102717375"}, {"first_name"=>"Michael K.", "last_name"=>"Skinner", "scopus_author_id"=>"7202488893"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84875527276", "sgr"=>"84875527276", "pui"=>"368612300", "isbn"=>"1932-6203 (Electronic) 1932-6203 (Linking)", "pmid"=>"23555832", "doi"=>"10.1371/journal.pone.0059922"}, "id"=>"1517836d-a98e-33c1-860f-c7b626d2ff72", "abstract"=>"Environmental toxicants have been shown to induce the epigenetic transgenerational inheritance of adult onset disease, including testis disease and male infertility. The current study was designed to determine the impact of an altered sperm epigenome on the subsequent development of an adult somatic cell {(Sertoli} cell) that influences the onset of a specific disease (male infertility). A gestating female rat {(F0} generation) was exposed to the agriculture fungicide vinclozolin during gonadal sex determination and then the subsequent F3 generation progeny used for the isolation of Sertoli cells and assessment of testis disease. As previously observed, enhanced spermatogenic cell apoptosis was observed. The Sertoli cells provide the physical and nutritional support for the spermatogenic cells. Over 400 genes were differentially expressed in the F3 generation control versus vinclozolin lineage Sertoli cells. A number of specific cellular pathways were identified to be transgenerationally altered. One of the key metabolic processes affected was pyruvate/lactate production that is directly linked to spermatogenic cell viability. The Sertoli cell epigenome was also altered with over 100 promoter differential {DNA} methylation regions {(DMR)} modified. The genomic features and overlap with the sperm {DMR} were investigated. Observations demonstrate that the transgenerational sperm epigenetic alterations subsequently alters the development of a specific somatic cell {(Sertoli} cell) epigenome and transcriptome that correlates with adult onset disease (male infertility). The environmentally induced epigenetic transgenerational inheritance of testis disease appears to be a component of the molecular etiology of male infertility.", "link"=>"http://www.mendeley.com/research/environmentally-induced-epigenetic-transgenerational-inheritance-altered-sertoli-cell-transcriptome", "reader_count"=>66, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>12, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>19, "Student > Postgraduate"=>3, "Student > Master"=>12, "Other"=>4, "Student > Bachelor"=>4, "Lecturer > Senior Lecturer"=>1, "Professor"=>6}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>12, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>19, "Student > Postgraduate"=>3, "Student > Master"=>12, "Other"=>4, "Student > Bachelor"=>4, "Lecturer > Senior Lecturer"=>1, "Professor"=>6}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Engineering"=>2, "Environmental Science"=>4, "Biochemistry, Genetics and Molecular Biology"=>14, "Agricultural and Biological Sciences"=>29, "Medicine and Dentistry"=>7, "Neuroscience"=>4, "Pharmacology, Toxicology and Pharmaceutical Science"=>2, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>7}, "Neuroscience"=>{"Neuroscience"=>4}, "Chemistry"=>{"Chemistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>29}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>14}, "Unspecified"=>{"Unspecified"=>3}, "Environmental Science"=>{"Environmental Science"=>4}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>2}}, "reader_count_by_country"=>{"Brazil"=>1, "United Kingdom"=>1, "France"=>1, "Switzerland"=>1, "India"=>2}, "group_count"=>3}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1000552"], "description"=>"<p>Relative apoptotic spermatogenic cell number per testis section is presented. F1 and F3 generation control and vinclozolin lineage testis were examined with the mean ± SEM presented and asterisks (*) indicating a statistically significant difference (p<0.05).</p>", "links"=>[], "tags"=>["apoptosis", "1-year-old"], "article_id"=>662199, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Carlos Guerrero-Bosagna", "Marina Savenkova", "Md. Muksitul Haque", "Eric Nilsson", "Michael K. Skinner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0059922.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Spermatogenic_cell_apoptosis_in_1_year_old_males_/662199", "title"=>"Spermatogenic cell apoptosis in 1-year-old males.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-29 11:41:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/1000553"], "description"=>"<p>The number of genes associated with the different functional categories are presented for up-regulated (black bar) or down-regulated (gray bar).</p>", "links"=>[], "tags"=>["categories", "f3", "vinclozolin", "lineage", "sertoli", "cells", "differentially"], "article_id"=>662200, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Carlos Guerrero-Bosagna", "Marina Savenkova", "Md. Muksitul Haque", "Eric Nilsson", "Michael K. Skinner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0059922.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gene_functional_categories_in_F3_generation_vinclozolin_lineage_Sertoli_cells_differentially_expressed_gene_417_genes_/662200", "title"=>"Gene functional categories in F3 generation vinclozolin lineage Sertoli cells differentially expressed gene (417 genes).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-29 11:42:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/1000554"], "description"=>"<p>Pyruvate and lactate metabolic pathway with colored genes having significantly different altered expression in the F3 generation vinclozolin lineage Sertoli cells.</p>", "links"=>[], "tags"=>["lactate", "metabolic", "pathway", "colored", "genes", "having", "altered", "f3", "vinclozolin", "lineage", "sertoli"], "article_id"=>662201, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Carlos Guerrero-Bosagna", "Marina Savenkova", "Md. Muksitul Haque", "Eric Nilsson", "Michael K. Skinner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0059922.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pyruvate_and_lactate_metabolic_pathway_with_colored_genes_having_significantly_different_altered_expression_in_the_F3_generation_vinclozolin_lineage_Sertoli_cells_/662201", "title"=>"Pyruvate and lactate metabolic pathway with colored genes having significantly different altered expression in the F3 generation vinclozolin lineage Sertoli cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-29 11:42:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/1000555"], "description"=>"<p>Genes having direct connectivity are presented with cellular localizations indicated.</p>", "links"=>[], "tags"=>["sertoli", "differentially"], "article_id"=>662202, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Carlos Guerrero-Bosagna", "Marina Savenkova", "Md. Muksitul Haque", "Eric Nilsson", "Michael K. Skinner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0059922.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gene_network_of_Sertoli_cell_differentially_expressed_genes_/662202", "title"=>"Gene network of Sertoli cell differentially expressed genes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-29 11:43:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/1000556"], "description"=>"<p>The chromosomal number and relative size are presented. The DMR (arrow), gene expression changes (line) and over-represented clusters of gene expression (box) are indicated.</p>", "links"=>[], "tags"=>["localization", "differential", "dna", "methylation", "regions", "clusters"], "article_id"=>662203, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Carlos Guerrero-Bosagna", "Marina Savenkova", "Md. Muksitul Haque", "Eric Nilsson", "Michael K. Skinner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0059922.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Chromosomal_localization_of_differential_DNA_methylation_regions_DMR_differential_expressed_genes_and_clusters_of_gene_expression_/662203", "title"=>"Chromosomal localization of differential DNA methylation regions (DMR), differential expressed genes, and clusters of gene expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-29 11:43:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1000557"], "description"=>"<p>The number of DMR and CpG density (CpG/100 bp) range are presented.</p>", "links"=>[], "tags"=>["f3", "vinclozolin", "lineage", "sertoli"], "article_id"=>662204, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Carlos Guerrero-Bosagna", "Marina Savenkova", "Md. Muksitul Haque", "Eric Nilsson", "Michael K. Skinner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0059922.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CpG_density_of_the_F3_generation_vinclozolin_lineage_Sertoli_cell_DMR_/662204", "title"=>"CpG density of the F3 generation vinclozolin lineage Sertoli cell DMR.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-29 11:43:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/1000558"], "description"=>"<p>The chromosomal location in megabases is presented with all genes (horizontal lines) and regulated genes (gene symbols) listed. The DMR are listed in arrow heads.</p>", "links"=>[], "tags"=>["epigenetic", "chromosome"], "article_id"=>662205, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Carlos Guerrero-Bosagna", "Marina Savenkova", "Md. Muksitul Haque", "Eric Nilsson", "Michael K. Skinner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0059922.g007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Example_of_an_epigenetic_control_region_ECR_on_chromosome_10_/662205", "title"=>"Example of an epigenetic control region (ECR) on chromosome 10.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-29 11:44:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/1000559"], "description"=>"<p>The white genes are DMR associated genes and the colored genes differentially expressed genes.</p>", "links"=>[], "tags"=>["interactions", "dmr", "differentially", "genes", "f3", "vinclozolin", "lineage", "sertoli"], "article_id"=>662206, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Carlos Guerrero-Bosagna", "Marina Savenkova", "Md. Muksitul Haque", "Eric Nilsson", "Michael K. Skinner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0059922.g008"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gene_interactions_between_DMR_and_differentially_expressed_genes_in_F3_generation_vinclozolin_lineage_Sertoli_cells_/662206", "title"=>"Gene interactions between DMR and differentially expressed genes in F3 generation vinclozolin lineage Sertoli cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-29 11:44:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/1000560"], "description"=>"<p>The genes identified in the literature associated with male infertility and testis disease that correlate with F3 generation vinclozolin lineage DMR and differentially expressed genes are presented.</p>", "links"=>[], "tags"=>["differentially", "genes", "correlate"], "article_id"=>662207, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Carlos Guerrero-Bosagna", "Marina Savenkova", "Md. Muksitul Haque", "Eric Nilsson", "Michael K. Skinner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0059922.g009"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DMR_and_differentially_expressed_genes_that_correlate_with_male_infertility_testis_disease_/662207", "title"=>"DMR and differentially expressed genes that correlate with male infertility/testis disease.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-29 11:44:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/1000561", "https://ndownloader.figshare.com/files/1000562", "https://ndownloader.figshare.com/files/1000563", "https://ndownloader.figshare.com/files/1000564", "https://ndownloader.figshare.com/files/1000566", "https://ndownloader.figshare.com/files/1000567", "https://ndownloader.figshare.com/files/1000568"], "description"=>"<div><p>Environmental toxicants have been shown to induce the epigenetic transgenerational inheritance of adult onset disease, including testis disease and male infertility. The current study was designed to determine the impact of an altered sperm epigenome on the subsequent development of an adult somatic cell (Sertoli cell) that influences the onset of a specific disease (male infertility). A gestating female rat (F0 generation) was exposed to the agriculture fungicide vinclozolin during gonadal sex determination and then the subsequent F3 generation progeny used for the isolation of Sertoli cells and assessment of testis disease. As previously observed, enhanced spermatogenic cell apoptosis was observed. The Sertoli cells provide the physical and nutritional support for the spermatogenic cells. Over 400 genes were differentially expressed in the F3 generation control versus vinclozolin lineage Sertoli cells. A number of specific cellular pathways were identified to be transgenerationally altered. One of the key metabolic processes affected was pyruvate/lactate production that is directly linked to spermatogenic cell viability. The Sertoli cell epigenome was also altered with over 100 promoter differential DNA methylation regions (DMR) modified. The genomic features and overlap with the sperm DMR were investigated. Observations demonstrate that the transgenerational sperm epigenetic alterations subsequently alters the development of a specific somatic cell (Sertoli cell) epigenome and transcriptome that correlates with adult onset disease (male infertility). The environmentally induced epigenetic transgenerational inheritance of testis disease appears to be a component of the molecular etiology of male infertility.</p> </div>", "links"=>[], "tags"=>["induced", "epigenetic", "transgenerational", "inheritance", "altered", "sertoli", "transcriptome", "molecular", "etiology"], "article_id"=>662208, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Carlos Guerrero-Bosagna", "Marina Savenkova", "Md. Muksitul Haque", "Eric Nilsson", "Michael K. Skinner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0059922.s001", "https://dx.doi.org/10.1371/journal.pone.0059922.s002", "https://dx.doi.org/10.1371/journal.pone.0059922.s003", "https://dx.doi.org/10.1371/journal.pone.0059922.s004", "https://dx.doi.org/10.1371/journal.pone.0059922.s005", "https://dx.doi.org/10.1371/journal.pone.0059922.s006", "https://dx.doi.org/10.1371/journal.pone.0059922.s007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Environmentally_Induced_Epigenetic_Transgenerational_Inheritance_of_Altered_Sertoli_Cell_Transcriptome_and_Epigenome_Molecular_Etiology_of_Male_Infertility_/662208", "title"=>"Environmentally Induced Epigenetic Transgenerational Inheritance of Altered Sertoli Cell Transcriptome and Epigenome: Molecular Etiology of Male Infertility", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-03-29 11:44:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/1008485"], "description"=>"<p>Associated Functional Pathway Categories.</p>", "links"=>[], "tags"=>["pathway"], "article_id"=>669112, "categories"=>["Genetics", "Developmental Biology"], "users"=>["Carlos Guerrero-Bosagna", "Marina Savenkova", "Md. Muksitul Haque", "Eric Nilsson", "Michael K. Skinner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0059922.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Associated_Functional_Pathway_Categories_/669112", "title"=>"Associated Functional Pathway Categories.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-03-28 02:31:52"}

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Relative Metric

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