Prenatal exposure to TCDD triggers significant modulation of microRNA expression profile in the thymus that affects consequent gene expression
MicroRNAs (miRs) are a class of small RNAs that regulate gene expression. There are over 700 miRs encoded in the mouse genome and modulate most of the cellular pathways and functions by controlling gene expression. However, there is not much known about the pathophysiological role of miRs. TCDD (2,3...
Gespeichert in:
| Veröffentlicht in: | PloS one 2012-09, Vol.7 (9), p.e45054 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 9 |
| container_start_page | e45054 |
| container_title | PloS one |
| container_volume | 7 |
| creator | Singh, Narendra P Singh, Udai P Guan, Hongbing Nagarkatti, Prakash Nagarkatti, Mitzi |
| description | MicroRNAs (miRs) are a class of small RNAs that regulate gene expression. There are over 700 miRs encoded in the mouse genome and modulate most of the cellular pathways and functions by controlling gene expression. However, there is not much known about the pathophysiological role of miRs. TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), an environmental contaminant is well known to induce severe toxicity (acute and chronic) with long-term effects. Also, in utero exposure of fetus to TCDD has been shown to cause thymic atrophy and alterations in T cell differentiation. It is also relevant to understand "the fetal basis of adult disease" hypothesis, which proposes that prenatal exposure to certain forms of nutritional and environmental stress can cause increased susceptibility to clinical disorders later in life. In the current study, therefore, we investigated the effects of prenatal exposure to TCDD on miR profile in fetal thymocytes and searched for their possible role in causing thymic atrophy and alterations in the expression of apoptotic genes.
miR arrays of fetal thymocytes post exposure to TCDD and vehicle were performed. Of the 608 mouse miRs screened, 78 miRs were altered more than 1.5 fold and 28 miRs were changed more than 2 fold in fetal thymocytes post-TCDD exposure when compared to vehicle controls. We validated the expression of several of the miRs using RT-PCR. Furthermore, several of the miRs that were downregulated contained highly complementary sequence to the 3'-UTR region of AhR, CYP1A1, Fas and FasL. Also, the Ingenuity Pathway Analysis software and database was used to analyze the 78 miRs that exhibited significant expression changes and revealed that as many as 15 pathways may be affected.
These studies revealed that TCDD-mediated alterations in miR expression may be involved in the regulation of its toxicity including cancer, hepatic injury, apoptosis, and cellular development. |
| doi_str_mv | 10.1371/journal.pone.0045054 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1326548359</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A543318585</galeid><doaj_id>oai_doaj_org_article_819382bc029d4bfbbcc9350b2bee3268</doaj_id><sourcerecordid>A543318585</sourcerecordid><originalsourceid>FETCH-LOGICAL-c692t-50ec2bdeb63b2ddaaa7d7a58e0bfccd28ea3726069bf214f91bd505d5d3558543</originalsourceid><addsrcrecordid>eNqNk12L1DAUhoso7rr6D0QDguDFjGnSdNobYZj1Y2BxZV29Dfk46WRomzFJZfdP-JtNne4yAwrSi5T0ed_mvDkny57neJ7TRf526wbfi3a-cz3MMS4YZsWD7DSvKZmVBNOHB-8n2ZMQthgzWpXl4-yEUEyKRZ2fZr--eOhFFC2Cm50LgwcUHbpenZ-j6G3TgA8o2Ka3xirRR9Q5PbQiWtcjZ1BnlXdXn5ej2EMI4_bOO2NbQLZHcZPcNrfdENIiIhLGgIoBKdcH-DFA8mughwP10-yREW2AZ9N6ln378P569Wl2cflxvVpezFRZkzhjGBSRGmRJJdFaCLHQC8EqwNIopUkFgi5IictaGpIXps6lTvlopiljFSvoWfZy77trXeBTlIHnlJSsqCirE7HeE9qJLd952wl_y52w_M-G8w0XPlrVAq9SzhWRCpNaF9JIqVRNGZZEAiTDKnm9m_42yA60SoV70R6ZHn_p7YY37ienRUEJHg1eTQbepdxC_MeRJ6oR6VS2Ny6Zqc4GxZepZppXqfZEzf9CpUdDus7UTOPtHQveHAkSE-EmNmIIga-_Xv0_e_n9mH19wG5AtHETXDuMzRWOwWIPpmYLwYO5Ty7HfJyFuzT4OAt8moUke3GY-r3orvnpb0KGCD4</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1326548359</pqid></control><display><type>article</type><title>Prenatal exposure to TCDD triggers significant modulation of microRNA expression profile in the thymus that affects consequent gene expression</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Public Library of Science (PLoS)</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Singh, Narendra P ; Singh, Udai P ; Guan, Hongbing ; Nagarkatti, Prakash ; Nagarkatti, Mitzi</creator><contributor>Kumar, Nirbhay</contributor><creatorcontrib>Singh, Narendra P ; Singh, Udai P ; Guan, Hongbing ; Nagarkatti, Prakash ; Nagarkatti, Mitzi ; Kumar, Nirbhay</creatorcontrib><description>MicroRNAs (miRs) are a class of small RNAs that regulate gene expression. There are over 700 miRs encoded in the mouse genome and modulate most of the cellular pathways and functions by controlling gene expression. However, there is not much known about the pathophysiological role of miRs. TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), an environmental contaminant is well known to induce severe toxicity (acute and chronic) with long-term effects. Also, in utero exposure of fetus to TCDD has been shown to cause thymic atrophy and alterations in T cell differentiation. It is also relevant to understand "the fetal basis of adult disease" hypothesis, which proposes that prenatal exposure to certain forms of nutritional and environmental stress can cause increased susceptibility to clinical disorders later in life. In the current study, therefore, we investigated the effects of prenatal exposure to TCDD on miR profile in fetal thymocytes and searched for their possible role in causing thymic atrophy and alterations in the expression of apoptotic genes.
miR arrays of fetal thymocytes post exposure to TCDD and vehicle were performed. Of the 608 mouse miRs screened, 78 miRs were altered more than 1.5 fold and 28 miRs were changed more than 2 fold in fetal thymocytes post-TCDD exposure when compared to vehicle controls. We validated the expression of several of the miRs using RT-PCR. Furthermore, several of the miRs that were downregulated contained highly complementary sequence to the 3'-UTR region of AhR, CYP1A1, Fas and FasL. Also, the Ingenuity Pathway Analysis software and database was used to analyze the 78 miRs that exhibited significant expression changes and revealed that as many as 15 pathways may be affected.
These studies revealed that TCDD-mediated alterations in miR expression may be involved in the regulation of its toxicity including cancer, hepatic injury, apoptosis, and cellular development.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0045054</identifier><identifier>PMID: 23024791</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>3' Untranslated regions ; Analysis ; Animal genetics ; Animals ; Apoptosis ; Apoptosis - drug effects ; Apoptosis - genetics ; Atrophy ; Biology ; Biomarkers ; Cancer ; Cell cycle ; Cell differentiation ; Cluster Analysis ; Contaminants ; Cytochrome P-450 CYP1A1 - genetics ; Cytochrome P-450 CYP1A1 - metabolism ; Cytochrome P450 ; Differentiation (biology) ; Dioxins ; Disease susceptibility ; Environmental stress ; Enzymes ; Exposure ; Fas Ligand Protein - genetics ; Fas Ligand Protein - metabolism ; fas Receptor - genetics ; fas Receptor - metabolism ; FasL protein ; Female ; Fetal alcohol syndrome ; Fetuses ; Gene expression ; Gene Expression Profiling ; Gene Expression Regulation, Developmental - drug effects ; Gene Regulatory Networks ; Genes ; Genomes ; Genomics ; Herbicides ; Hydrocarbons ; Immunology ; Intrauterine exposure ; Long-term effects ; Lymphocytes T ; Maternal Exposure ; Medicine ; Mice ; MicroRNA ; MicroRNAs ; MicroRNAs - genetics ; miRNA ; Neoplasms - genetics ; Nutrient deficiency ; Pathology ; Pathways ; Polychlorinated Dibenzodioxins - pharmacology ; Polychlorinated Dibenzodioxins - toxicity ; Polymerase chain reaction ; Pregnancy ; Pregnant women ; Prenatal experience ; Prenatal exposure ; Prostate cancer ; Receptors, Aryl Hydrocarbon - genetics ; Receptors, Aryl Hydrocarbon - metabolism ; Reproducibility of Results ; Ribonucleic acid ; RNA ; Rodents ; Signal Transduction - drug effects ; T cells ; TCDD ; Thymocytes ; Thymocytes - drug effects ; Thymocytes - metabolism ; Thymus ; Thymus Gland - drug effects ; Thymus Gland - embryology ; Thymus Gland - metabolism ; Toxicity</subject><ispartof>PloS one, 2012-09, Vol.7 (9), p.e45054</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>Singh et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2012 Singh et al 2012 Singh et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-50ec2bdeb63b2ddaaa7d7a58e0bfccd28ea3726069bf214f91bd505d5d3558543</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3443208/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3443208/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2100,2926,23864,27922,27923,53789,53791,79370,79371</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23024791$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Kumar, Nirbhay</contributor><creatorcontrib>Singh, Narendra P</creatorcontrib><creatorcontrib>Singh, Udai P</creatorcontrib><creatorcontrib>Guan, Hongbing</creatorcontrib><creatorcontrib>Nagarkatti, Prakash</creatorcontrib><creatorcontrib>Nagarkatti, Mitzi</creatorcontrib><title>Prenatal exposure to TCDD triggers significant modulation of microRNA expression profile in the thymus that affects consequent gene expression</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>MicroRNAs (miRs) are a class of small RNAs that regulate gene expression. There are over 700 miRs encoded in the mouse genome and modulate most of the cellular pathways and functions by controlling gene expression. However, there is not much known about the pathophysiological role of miRs. TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), an environmental contaminant is well known to induce severe toxicity (acute and chronic) with long-term effects. Also, in utero exposure of fetus to TCDD has been shown to cause thymic atrophy and alterations in T cell differentiation. It is also relevant to understand "the fetal basis of adult disease" hypothesis, which proposes that prenatal exposure to certain forms of nutritional and environmental stress can cause increased susceptibility to clinical disorders later in life. In the current study, therefore, we investigated the effects of prenatal exposure to TCDD on miR profile in fetal thymocytes and searched for their possible role in causing thymic atrophy and alterations in the expression of apoptotic genes.
miR arrays of fetal thymocytes post exposure to TCDD and vehicle were performed. Of the 608 mouse miRs screened, 78 miRs were altered more than 1.5 fold and 28 miRs were changed more than 2 fold in fetal thymocytes post-TCDD exposure when compared to vehicle controls. We validated the expression of several of the miRs using RT-PCR. Furthermore, several of the miRs that were downregulated contained highly complementary sequence to the 3'-UTR region of AhR, CYP1A1, Fas and FasL. Also, the Ingenuity Pathway Analysis software and database was used to analyze the 78 miRs that exhibited significant expression changes and revealed that as many as 15 pathways may be affected.
These studies revealed that TCDD-mediated alterations in miR expression may be involved in the regulation of its toxicity including cancer, hepatic injury, apoptosis, and cellular development.</description><subject>3' Untranslated regions</subject><subject>Analysis</subject><subject>Animal genetics</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - genetics</subject><subject>Atrophy</subject><subject>Biology</subject><subject>Biomarkers</subject><subject>Cancer</subject><subject>Cell cycle</subject><subject>Cell differentiation</subject><subject>Cluster Analysis</subject><subject>Contaminants</subject><subject>Cytochrome P-450 CYP1A1 - genetics</subject><subject>Cytochrome P-450 CYP1A1 - metabolism</subject><subject>Cytochrome P450</subject><subject>Differentiation (biology)</subject><subject>Dioxins</subject><subject>Disease susceptibility</subject><subject>Environmental stress</subject><subject>Enzymes</subject><subject>Exposure</subject><subject>Fas Ligand Protein - genetics</subject><subject>Fas Ligand Protein - metabolism</subject><subject>fas Receptor - genetics</subject><subject>fas Receptor - metabolism</subject><subject>FasL protein</subject><subject>Female</subject><subject>Fetal alcohol syndrome</subject><subject>Fetuses</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Developmental - drug effects</subject><subject>Gene Regulatory Networks</subject><subject>Genes</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Herbicides</subject><subject>Hydrocarbons</subject><subject>Immunology</subject><subject>Intrauterine exposure</subject><subject>Long-term effects</subject><subject>Lymphocytes T</subject><subject>Maternal Exposure</subject><subject>Medicine</subject><subject>Mice</subject><subject>MicroRNA</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>miRNA</subject><subject>Neoplasms - genetics</subject><subject>Nutrient deficiency</subject><subject>Pathology</subject><subject>Pathways</subject><subject>Polychlorinated Dibenzodioxins - pharmacology</subject><subject>Polychlorinated Dibenzodioxins - toxicity</subject><subject>Polymerase chain reaction</subject><subject>Pregnancy</subject><subject>Pregnant women</subject><subject>Prenatal experience</subject><subject>Prenatal exposure</subject><subject>Prostate cancer</subject><subject>Receptors, Aryl Hydrocarbon - genetics</subject><subject>Receptors, Aryl Hydrocarbon - metabolism</subject><subject>Reproducibility of Results</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Rodents</subject><subject>Signal Transduction - drug effects</subject><subject>T cells</subject><subject>TCDD</subject><subject>Thymocytes</subject><subject>Thymocytes - drug effects</subject><subject>Thymocytes - metabolism</subject><subject>Thymus</subject><subject>Thymus Gland - drug effects</subject><subject>Thymus Gland - embryology</subject><subject>Thymus Gland - metabolism</subject><subject>Toxicity</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12L1DAUhoso7rr6D0QDguDFjGnSdNobYZj1Y2BxZV29Dfk46WRomzFJZfdP-JtNne4yAwrSi5T0ed_mvDkny57neJ7TRf526wbfi3a-cz3MMS4YZsWD7DSvKZmVBNOHB-8n2ZMQthgzWpXl4-yEUEyKRZ2fZr--eOhFFC2Cm50LgwcUHbpenZ-j6G3TgA8o2Ka3xirRR9Q5PbQiWtcjZ1BnlXdXn5ej2EMI4_bOO2NbQLZHcZPcNrfdENIiIhLGgIoBKdcH-DFA8mughwP10-yREW2AZ9N6ln378P569Wl2cflxvVpezFRZkzhjGBSRGmRJJdFaCLHQC8EqwNIopUkFgi5IictaGpIXps6lTvlopiljFSvoWfZy77trXeBTlIHnlJSsqCirE7HeE9qJLd952wl_y52w_M-G8w0XPlrVAq9SzhWRCpNaF9JIqVRNGZZEAiTDKnm9m_42yA60SoV70R6ZHn_p7YY37ienRUEJHg1eTQbepdxC_MeRJ6oR6VS2Ny6Zqc4GxZepZppXqfZEzf9CpUdDus7UTOPtHQveHAkSE-EmNmIIga-_Xv0_e_n9mH19wG5AtHETXDuMzRWOwWIPpmYLwYO5Ty7HfJyFuzT4OAt8moUke3GY-r3orvnpb0KGCD4</recordid><startdate>20120914</startdate><enddate>20120914</enddate><creator>Singh, Narendra P</creator><creator>Singh, Udai P</creator><creator>Guan, Hongbing</creator><creator>Nagarkatti, Prakash</creator><creator>Nagarkatti, Mitzi</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20120914</creationdate><title>Prenatal exposure to TCDD triggers significant modulation of microRNA expression profile in the thymus that affects consequent gene expression</title><author>Singh, Narendra P ; Singh, Udai P ; Guan, Hongbing ; Nagarkatti, Prakash ; Nagarkatti, Mitzi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-50ec2bdeb63b2ddaaa7d7a58e0bfccd28ea3726069bf214f91bd505d5d3558543</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>3' Untranslated regions</topic><topic>Analysis</topic><topic>Animal genetics</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis - genetics</topic><topic>Atrophy</topic><topic>Biology</topic><topic>Biomarkers</topic><topic>Cancer</topic><topic>Cell cycle</topic><topic>Cell differentiation</topic><topic>Cluster Analysis</topic><topic>Contaminants</topic><topic>Cytochrome P-450 CYP1A1 - genetics</topic><topic>Cytochrome P-450 CYP1A1 - metabolism</topic><topic>Cytochrome P450</topic><topic>Differentiation (biology)</topic><topic>Dioxins</topic><topic>Disease susceptibility</topic><topic>Environmental stress</topic><topic>Enzymes</topic><topic>Exposure</topic><topic>Fas Ligand Protein - genetics</topic><topic>Fas Ligand Protein - metabolism</topic><topic>fas Receptor - genetics</topic><topic>fas Receptor - metabolism</topic><topic>FasL protein</topic><topic>Female</topic><topic>Fetal alcohol syndrome</topic><topic>Fetuses</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Developmental - drug effects</topic><topic>Gene Regulatory Networks</topic><topic>Genes</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Herbicides</topic><topic>Hydrocarbons</topic><topic>Immunology</topic><topic>Intrauterine exposure</topic><topic>Long-term effects</topic><topic>Lymphocytes T</topic><topic>Maternal Exposure</topic><topic>Medicine</topic><topic>Mice</topic><topic>MicroRNA</topic><topic>MicroRNAs</topic><topic>MicroRNAs - genetics</topic><topic>miRNA</topic><topic>Neoplasms - genetics</topic><topic>Nutrient deficiency</topic><topic>Pathology</topic><topic>Pathways</topic><topic>Polychlorinated Dibenzodioxins - pharmacology</topic><topic>Polychlorinated Dibenzodioxins - toxicity</topic><topic>Polymerase chain reaction</topic><topic>Pregnancy</topic><topic>Pregnant women</topic><topic>Prenatal experience</topic><topic>Prenatal exposure</topic><topic>Prostate cancer</topic><topic>Receptors, Aryl Hydrocarbon - genetics</topic><topic>Receptors, Aryl Hydrocarbon - metabolism</topic><topic>Reproducibility of Results</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>Rodents</topic><topic>Signal Transduction - drug effects</topic><topic>T cells</topic><topic>TCDD</topic><topic>Thymocytes</topic><topic>Thymocytes - drug effects</topic><topic>Thymocytes - metabolism</topic><topic>Thymus</topic><topic>Thymus Gland - drug effects</topic><topic>Thymus Gland - embryology</topic><topic>Thymus Gland - metabolism</topic><topic>Toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Singh, Narendra P</creatorcontrib><creatorcontrib>Singh, Udai P</creatorcontrib><creatorcontrib>Guan, Hongbing</creatorcontrib><creatorcontrib>Nagarkatti, Prakash</creatorcontrib><creatorcontrib>Nagarkatti, Mitzi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Singh, Narendra P</au><au>Singh, Udai P</au><au>Guan, Hongbing</au><au>Nagarkatti, Prakash</au><au>Nagarkatti, Mitzi</au><au>Kumar, Nirbhay</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prenatal exposure to TCDD triggers significant modulation of microRNA expression profile in the thymus that affects consequent gene expression</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-09-14</date><risdate>2012</risdate><volume>7</volume><issue>9</issue><spage>e45054</spage><pages>e45054-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>MicroRNAs (miRs) are a class of small RNAs that regulate gene expression. There are over 700 miRs encoded in the mouse genome and modulate most of the cellular pathways and functions by controlling gene expression. However, there is not much known about the pathophysiological role of miRs. TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), an environmental contaminant is well known to induce severe toxicity (acute and chronic) with long-term effects. Also, in utero exposure of fetus to TCDD has been shown to cause thymic atrophy and alterations in T cell differentiation. It is also relevant to understand "the fetal basis of adult disease" hypothesis, which proposes that prenatal exposure to certain forms of nutritional and environmental stress can cause increased susceptibility to clinical disorders later in life. In the current study, therefore, we investigated the effects of prenatal exposure to TCDD on miR profile in fetal thymocytes and searched for their possible role in causing thymic atrophy and alterations in the expression of apoptotic genes.
miR arrays of fetal thymocytes post exposure to TCDD and vehicle were performed. Of the 608 mouse miRs screened, 78 miRs were altered more than 1.5 fold and 28 miRs were changed more than 2 fold in fetal thymocytes post-TCDD exposure when compared to vehicle controls. We validated the expression of several of the miRs using RT-PCR. Furthermore, several of the miRs that were downregulated contained highly complementary sequence to the 3'-UTR region of AhR, CYP1A1, Fas and FasL. Also, the Ingenuity Pathway Analysis software and database was used to analyze the 78 miRs that exhibited significant expression changes and revealed that as many as 15 pathways may be affected.
These studies revealed that TCDD-mediated alterations in miR expression may be involved in the regulation of its toxicity including cancer, hepatic injury, apoptosis, and cellular development.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23024791</pmid><doi>10.1371/journal.pone.0045054</doi><tpages>e45054</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2012-09, Vol.7 (9), p.e45054 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1326548359 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 3' Untranslated regions Analysis Animal genetics Animals Apoptosis Apoptosis - drug effects Apoptosis - genetics Atrophy Biology Biomarkers Cancer Cell cycle Cell differentiation Cluster Analysis Contaminants Cytochrome P-450 CYP1A1 - genetics Cytochrome P-450 CYP1A1 - metabolism Cytochrome P450 Differentiation (biology) Dioxins Disease susceptibility Environmental stress Enzymes Exposure Fas Ligand Protein - genetics Fas Ligand Protein - metabolism fas Receptor - genetics fas Receptor - metabolism FasL protein Female Fetal alcohol syndrome Fetuses Gene expression Gene Expression Profiling Gene Expression Regulation, Developmental - drug effects Gene Regulatory Networks Genes Genomes Genomics Herbicides Hydrocarbons Immunology Intrauterine exposure Long-term effects Lymphocytes T Maternal Exposure Medicine Mice MicroRNA MicroRNAs MicroRNAs - genetics miRNA Neoplasms - genetics Nutrient deficiency Pathology Pathways Polychlorinated Dibenzodioxins - pharmacology Polychlorinated Dibenzodioxins - toxicity Polymerase chain reaction Pregnancy Pregnant women Prenatal experience Prenatal exposure Prostate cancer Receptors, Aryl Hydrocarbon - genetics Receptors, Aryl Hydrocarbon - metabolism Reproducibility of Results Ribonucleic acid RNA Rodents Signal Transduction - drug effects T cells TCDD Thymocytes Thymocytes - drug effects Thymocytes - metabolism Thymus Thymus Gland - drug effects Thymus Gland - embryology Thymus Gland - metabolism Toxicity |
| title | Prenatal exposure to TCDD triggers significant modulation of microRNA expression profile in the thymus that affects consequent gene expression |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-14T01%3A49%3A16IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Prenatal%20exposure%20to%20TCDD%20triggers%20significant%20modulation%20of%20microRNA%20expression%20profile%20in%20the%20thymus%20that%20affects%20consequent%20gene%20expression&rft.jtitle=PloS%20one&rft.au=Singh,%20Narendra%20P&rft.date=2012-09-14&rft.volume=7&rft.issue=9&rft.spage=e45054&rft.pages=e45054-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0045054&rft_dat=%3Cgale_plos_%3EA543318585%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1326548359&rft_id=info:pmid/23024791&rft_galeid=A543318585&rft_doaj_id=oai_doaj_org_article_819382bc029d4bfbbcc9350b2bee3268&rfr_iscdi=true |