Valproic acid-induced gene expression responses in rat whole embryo culture and comparison across in vitro developmental and non-developmental models
•Transcriptomics was used to identify VPA-induced gene expression changes in WEC.•VPA-induced responses were compared across in vitro-based developmental models.•We observed conservation of VPA-induced gene regulation across in vitro developmental models.•Developmental models provide added value whe...
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| Veröffentlicht in: | Reproductive toxicology (Elmsford, N.Y.) N.Y.), 2013-11, Vol.41, p.57-66 |
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| creator | Tonk, Elisa C.M. Robinson, Joshua F. Verhoef, Aart Theunissen, Peter T. Pennings, Jeroen L.A. Piersma, Aldert H. |
| description | •Transcriptomics was used to identify VPA-induced gene expression changes in WEC.•VPA-induced responses were compared across in vitro-based developmental models.•We observed conservation of VPA-induced gene regulation across in vitro developmental models.•Developmental models provide added value when assessing developmental-specific effects.
Transcriptomic evaluations may improve toxicity prediction of in vitro-based developmental models. In this study, transcriptomics was used to identify VPA-induced gene expression changes in rat whole embryo culture (WEC). Furthermore, VPA-induced responses were compared across in vitro-based developmental models, such as the cardiac and neural embryonic stem cells (ESTc and ESTn, respectively) and the zebrafish embryotoxicity model. VPA-induced gene regulation in WEC corresponded with observed morphological effects and previously suggested mechanisms of toxicity. Gene Ontology term-directed analysis showed conservation of VPA-induced gene expression changes across in vitro-based developmental models, with ESTc and ESTn exhibiting complementary responses. Furthermore, comparison of in vitro-based developmental and non-developmental models revealed that more generalized VPA-induced effects can be detected using non-developmental models whereas developmental models provide added value when assessing developmental-specific effects. These analyses can be used to optimize test batteries for the detection of developmental toxicants in vitro. |
| doi_str_mv | 10.1016/j.reprotox.2013.06.069 |
| format | Article |
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Transcriptomic evaluations may improve toxicity prediction of in vitro-based developmental models. In this study, transcriptomics was used to identify VPA-induced gene expression changes in rat whole embryo culture (WEC). Furthermore, VPA-induced responses were compared across in vitro-based developmental models, such as the cardiac and neural embryonic stem cells (ESTc and ESTn, respectively) and the zebrafish embryotoxicity model. VPA-induced gene regulation in WEC corresponded with observed morphological effects and previously suggested mechanisms of toxicity. Gene Ontology term-directed analysis showed conservation of VPA-induced gene expression changes across in vitro-based developmental models, with ESTc and ESTn exhibiting complementary responses. Furthermore, comparison of in vitro-based developmental and non-developmental models revealed that more generalized VPA-induced effects can be detected using non-developmental models whereas developmental models provide added value when assessing developmental-specific effects. These analyses can be used to optimize test batteries for the detection of developmental toxicants in vitro.</description><identifier>ISSN: 0890-6238</identifier><identifier>EISSN: 1873-1708</identifier><identifier>DOI: 10.1016/j.reprotox.2013.06.069</identifier><identifier>PMID: 23811354</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Danio rerio ; Embryo ; Embryo, Mammalian - abnormalities ; Embryo, Mammalian - drug effects ; Embryo, Mammalian - metabolism ; Embryo, Nonmammalian - drug effects ; Embryo, Nonmammalian - metabolism ; Embryonic Stem Cells - drug effects ; Embryonic Stem Cells - metabolism ; Gene expression ; Gene Expression Profiling ; Gene Expression Regulation, Developmental - drug effects ; In vitro ; Oligonucleotide Array Sequence Analysis ; Rats ; Rats, Wistar ; Teratogens - toxicity ; Transcriptomics ; Valproic acid ; Valproic Acid - toxicity ; Whole embryo culture ; Zebrafish</subject><ispartof>Reproductive toxicology (Elmsford, N.Y.), 2013-11, Vol.41, p.57-66</ispartof><rights>2013 Elsevier Inc.</rights><rights>Copyright © 2013 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c401t-b165224c4baff2ce73352506ebc660236035feeae4f0aaa9143ed45b8954b2df3</citedby><cites>FETCH-LOGICAL-c401t-b165224c4baff2ce73352506ebc660236035feeae4f0aaa9143ed45b8954b2df3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.reprotox.2013.06.069$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23811354$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tonk, Elisa C.M.</creatorcontrib><creatorcontrib>Robinson, Joshua F.</creatorcontrib><creatorcontrib>Verhoef, Aart</creatorcontrib><creatorcontrib>Theunissen, Peter T.</creatorcontrib><creatorcontrib>Pennings, Jeroen L.A.</creatorcontrib><creatorcontrib>Piersma, Aldert H.</creatorcontrib><title>Valproic acid-induced gene expression responses in rat whole embryo culture and comparison across in vitro developmental and non-developmental models</title><title>Reproductive toxicology (Elmsford, N.Y.)</title><addtitle>Reprod Toxicol</addtitle><description>•Transcriptomics was used to identify VPA-induced gene expression changes in WEC.•VPA-induced responses were compared across in vitro-based developmental models.•We observed conservation of VPA-induced gene regulation across in vitro developmental models.•Developmental models provide added value when assessing developmental-specific effects.
Transcriptomic evaluations may improve toxicity prediction of in vitro-based developmental models. In this study, transcriptomics was used to identify VPA-induced gene expression changes in rat whole embryo culture (WEC). Furthermore, VPA-induced responses were compared across in vitro-based developmental models, such as the cardiac and neural embryonic stem cells (ESTc and ESTn, respectively) and the zebrafish embryotoxicity model. VPA-induced gene regulation in WEC corresponded with observed morphological effects and previously suggested mechanisms of toxicity. Gene Ontology term-directed analysis showed conservation of VPA-induced gene expression changes across in vitro-based developmental models, with ESTc and ESTn exhibiting complementary responses. Furthermore, comparison of in vitro-based developmental and non-developmental models revealed that more generalized VPA-induced effects can be detected using non-developmental models whereas developmental models provide added value when assessing developmental-specific effects. These analyses can be used to optimize test batteries for the detection of developmental toxicants in vitro.</description><subject>Animals</subject><subject>Danio rerio</subject><subject>Embryo</subject><subject>Embryo, Mammalian - abnormalities</subject><subject>Embryo, Mammalian - drug effects</subject><subject>Embryo, Mammalian - metabolism</subject><subject>Embryo, Nonmammalian - drug effects</subject><subject>Embryo, Nonmammalian - metabolism</subject><subject>Embryonic Stem Cells - drug effects</subject><subject>Embryonic Stem Cells - metabolism</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Developmental - drug effects</subject><subject>In vitro</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Teratogens - toxicity</subject><subject>Transcriptomics</subject><subject>Valproic acid</subject><subject>Valproic Acid - toxicity</subject><subject>Whole embryo culture</subject><subject>Zebrafish</subject><issn>0890-6238</issn><issn>1873-1708</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFu1DAQhi0EokvbV6h85JJlHDtOcgNVlFaqxKXlajn2BLxy7GAnS_sgvC_ubovECWmk0Yy-f0YzPyEXDLYMmPyw2yacU1ziw7YGxrcgS_SvyIZ1La9YC91rsoGuh0rWvDsh73LeAYBo-_YtOSktxngjNuT3N-3LHGeoNs5WLtjVoKXfMSDFhzlhzi4GWvIcQ8ZMXSn0Qn_9iL4Q05AeIzWrX9aEVAdLTZxmnVwuIm1SzAfF3i0pUot79HGeMCzaH-AQQ_Vvd4oWfT4jb0btM54_51Nyf_X57vK6uv365eby021lBLClGphs6loYMehxrA22nDd1AxIHIyXUXAJvRkSNYgStdc8ERyuaoesbMdR25Kfk_XFuecHPFfOiJpcNeq8DxjUrJnkDXPZcFFQe0cNRCUc1Jzfp9KgYqCdL1E69WKKeLFEgS_RFePG8Yx0mtH9lLx4U4OMRKIfj3mFS2TgMxQaX0CzKRve_HX8AVWmltQ</recordid><startdate>201311</startdate><enddate>201311</enddate><creator>Tonk, Elisa C.M.</creator><creator>Robinson, Joshua F.</creator><creator>Verhoef, Aart</creator><creator>Theunissen, Peter T.</creator><creator>Pennings, Jeroen L.A.</creator><creator>Piersma, Aldert H.</creator><general>Elsevier Inc</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>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>201311</creationdate><title>Valproic acid-induced gene expression responses in rat whole embryo culture and comparison across in vitro developmental and non-developmental models</title><author>Tonk, Elisa C.M. ; Robinson, Joshua F. ; Verhoef, Aart ; Theunissen, Peter T. ; Pennings, Jeroen L.A. ; Piersma, Aldert H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c401t-b165224c4baff2ce73352506ebc660236035feeae4f0aaa9143ed45b8954b2df3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Danio rerio</topic><topic>Embryo</topic><topic>Embryo, Mammalian - abnormalities</topic><topic>Embryo, Mammalian - drug effects</topic><topic>Embryo, Mammalian - metabolism</topic><topic>Embryo, Nonmammalian - drug effects</topic><topic>Embryo, Nonmammalian - metabolism</topic><topic>Embryonic Stem Cells - drug effects</topic><topic>Embryonic Stem Cells - metabolism</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Developmental - drug effects</topic><topic>In vitro</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Teratogens - toxicity</topic><topic>Transcriptomics</topic><topic>Valproic acid</topic><topic>Valproic Acid - toxicity</topic><topic>Whole embryo culture</topic><topic>Zebrafish</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tonk, Elisa C.M.</creatorcontrib><creatorcontrib>Robinson, Joshua F.</creatorcontrib><creatorcontrib>Verhoef, Aart</creatorcontrib><creatorcontrib>Theunissen, Peter T.</creatorcontrib><creatorcontrib>Pennings, Jeroen L.A.</creatorcontrib><creatorcontrib>Piersma, Aldert H.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Reproductive toxicology (Elmsford, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tonk, Elisa C.M.</au><au>Robinson, Joshua F.</au><au>Verhoef, Aart</au><au>Theunissen, Peter T.</au><au>Pennings, Jeroen L.A.</au><au>Piersma, Aldert H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Valproic acid-induced gene expression responses in rat whole embryo culture and comparison across in vitro developmental and non-developmental models</atitle><jtitle>Reproductive toxicology (Elmsford, N.Y.)</jtitle><addtitle>Reprod Toxicol</addtitle><date>2013-11</date><risdate>2013</risdate><volume>41</volume><spage>57</spage><epage>66</epage><pages>57-66</pages><issn>0890-6238</issn><eissn>1873-1708</eissn><abstract>•Transcriptomics was used to identify VPA-induced gene expression changes in WEC.•VPA-induced responses were compared across in vitro-based developmental models.•We observed conservation of VPA-induced gene regulation across in vitro developmental models.•Developmental models provide added value when assessing developmental-specific effects.
Transcriptomic evaluations may improve toxicity prediction of in vitro-based developmental models. In this study, transcriptomics was used to identify VPA-induced gene expression changes in rat whole embryo culture (WEC). Furthermore, VPA-induced responses were compared across in vitro-based developmental models, such as the cardiac and neural embryonic stem cells (ESTc and ESTn, respectively) and the zebrafish embryotoxicity model. VPA-induced gene regulation in WEC corresponded with observed morphological effects and previously suggested mechanisms of toxicity. Gene Ontology term-directed analysis showed conservation of VPA-induced gene expression changes across in vitro-based developmental models, with ESTc and ESTn exhibiting complementary responses. Furthermore, comparison of in vitro-based developmental and non-developmental models revealed that more generalized VPA-induced effects can be detected using non-developmental models whereas developmental models provide added value when assessing developmental-specific effects. These analyses can be used to optimize test batteries for the detection of developmental toxicants in vitro.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>23811354</pmid><doi>10.1016/j.reprotox.2013.06.069</doi><tpages>10</tpages></addata></record> |
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| ispartof | Reproductive toxicology (Elmsford, N.Y.), 2013-11, Vol.41, p.57-66 |
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| subjects | Animals Danio rerio Embryo Embryo, Mammalian - abnormalities Embryo, Mammalian - drug effects Embryo, Mammalian - metabolism Embryo, Nonmammalian - drug effects Embryo, Nonmammalian - metabolism Embryonic Stem Cells - drug effects Embryonic Stem Cells - metabolism Gene expression Gene Expression Profiling Gene Expression Regulation, Developmental - drug effects In vitro Oligonucleotide Array Sequence Analysis Rats Rats, Wistar Teratogens - toxicity Transcriptomics Valproic acid Valproic Acid - toxicity Whole embryo culture Zebrafish |
| title | Valproic acid-induced gene expression responses in rat whole embryo culture and comparison across in vitro developmental and non-developmental models |
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