Trichostatin A rescues the disrupted imprinting induced by somatic cell nuclear transfer in pigs
Imprinting disorders induced by somatic cell nuclear transfer (SCNT) usually lead to the abnormalities of cloned animals and low cloning efficiency. Histone deacetylase inhibitors have been shown to improve gene expression, genomic methylation reprogramming and the development of cloned embryos, how...
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| description | Imprinting disorders induced by somatic cell nuclear transfer (SCNT) usually lead to the abnormalities of cloned animals and low cloning efficiency. Histone deacetylase inhibitors have been shown to improve gene expression, genomic methylation reprogramming and the development of cloned embryos, however, the imprinting statuses in these treated embryos and during their subsequent development remain poorly studied. In this study, we investigated the dynamics of H19/Igf2 methylation and transcription in porcine cloned embryos treated with trichostatin A (TSA), and examined H19/Igf2 imprinting patterns in cloned fetuses and piglets. Our results showed that compared with the maintenance of H19/Igf2 methylation in fertilized embryos, cloned embryos displayed aberrant H19/Igf2 methylation and lower H19/Igf2 transcripts. When TSA enhanced the development of cloned embryos, the disrupted H19/Igf2 imprinting was largely rescued in these treated embryos, more similar to those detected in fertilized counterparts. Further studies displayed that TSA effectively rescued the disrupted imprinting of H19/Igf2 in cloned fetuses and piglets, prevented the occurrence of cloned fetus and piglet abnormalities, and enhanced the full-term development of cloned embryos. In conclusion, our results demonstrated that aberrant imprinting induced by SCNT led to the abnormalities of cloned fetuses and piglets and low cloning efficiency, and TSA rescued the disrupted imprinting in cloned embryos, fetuses and piglets, and prevented the occurrence of cloned fetus and piglet abnormalities, thereby improving the development of cloned embryos. This study would have important implications in improving cloning efficiency and the health of cloned animals. |
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Histone deacetylase inhibitors have been shown to improve gene expression, genomic methylation reprogramming and the development of cloned embryos, however, the imprinting statuses in these treated embryos and during their subsequent development remain poorly studied. In this study, we investigated the dynamics of H19/Igf2 methylation and transcription in porcine cloned embryos treated with trichostatin A (TSA), and examined H19/Igf2 imprinting patterns in cloned fetuses and piglets. Our results showed that compared with the maintenance of H19/Igf2 methylation in fertilized embryos, cloned embryos displayed aberrant H19/Igf2 methylation and lower H19/Igf2 transcripts. When TSA enhanced the development of cloned embryos, the disrupted H19/Igf2 imprinting was largely rescued in these treated embryos, more similar to those detected in fertilized counterparts. Further studies displayed that TSA effectively rescued the disrupted imprinting of H19/Igf2 in cloned fetuses and piglets, prevented the occurrence of cloned fetus and piglet abnormalities, and enhanced the full-term development of cloned embryos. In conclusion, our results demonstrated that aberrant imprinting induced by SCNT led to the abnormalities of cloned fetuses and piglets and low cloning efficiency, and TSA rescued the disrupted imprinting in cloned embryos, fetuses and piglets, and prevented the occurrence of cloned fetus and piglet abnormalities, thereby improving the development of cloned embryos. This study would have important implications in improving cloning efficiency and the health of cloned animals.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0126607</identifier><identifier>PMID: 25962071</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aberration ; Abnormalities ; Animals ; Antifungal agents ; Cells, Cultured ; Cloning ; DNA methylation ; DNA Methylation - drug effects ; DNA Methylation - genetics ; Efficiency ; Embryos ; Epigenetics ; Female ; Fertilization in Vitro ; Fetuses ; Fibroblasts - drug effects ; Fibroblasts - metabolism ; Gene expression ; Genomic imprinting ; Genomic Imprinting - drug effects ; Genomic Imprinting - genetics ; Health aspects ; Histone deacetylase ; Hogs ; Hydroxamic Acids - pharmacology ; Imprinting ; Imprinting (Psychology) ; Insulin-like growth factor II ; Insulin-Like Growth Factor II - metabolism ; Nuclear transfer ; Nuclear transfer (Cloning) ; Nuclear Transfer Techniques ; Pregnancy ; Somatic cell nuclear transfer ; Suidae ; Swine ; Trichostatin A</subject><ispartof>PloS one, 2015-05, Vol.10 (5), p.e0126607-e0126607</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Huan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://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>2015 Huan et al 2015 Huan et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-15b8455fa3e5c6471a20cb682eb2c6c106112bb6504313d8252e9a1b97ef6ed83</citedby><cites>FETCH-LOGICAL-c692t-15b8455fa3e5c6471a20cb682eb2c6c106112bb6504313d8252e9a1b97ef6ed83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427324/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427324/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25962071$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Huan, Yanjun</creatorcontrib><creatorcontrib>Zhu, Jiang</creatorcontrib><creatorcontrib>Huang, Bo</creatorcontrib><creatorcontrib>Mu, Yanshuang</creatorcontrib><creatorcontrib>Kong, Qingran</creatorcontrib><creatorcontrib>Liu, Zhonghua</creatorcontrib><title>Trichostatin A rescues the disrupted imprinting induced by somatic cell nuclear transfer in pigs</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Imprinting disorders induced by somatic cell nuclear transfer (SCNT) usually lead to the abnormalities of cloned animals and low cloning efficiency. Histone deacetylase inhibitors have been shown to improve gene expression, genomic methylation reprogramming and the development of cloned embryos, however, the imprinting statuses in these treated embryos and during their subsequent development remain poorly studied. In this study, we investigated the dynamics of H19/Igf2 methylation and transcription in porcine cloned embryos treated with trichostatin A (TSA), and examined H19/Igf2 imprinting patterns in cloned fetuses and piglets. Our results showed that compared with the maintenance of H19/Igf2 methylation in fertilized embryos, cloned embryos displayed aberrant H19/Igf2 methylation and lower H19/Igf2 transcripts. When TSA enhanced the development of cloned embryos, the disrupted H19/Igf2 imprinting was largely rescued in these treated embryos, more similar to those detected in fertilized counterparts. Further studies displayed that TSA effectively rescued the disrupted imprinting of H19/Igf2 in cloned fetuses and piglets, prevented the occurrence of cloned fetus and piglet abnormalities, and enhanced the full-term development of cloned embryos. In conclusion, our results demonstrated that aberrant imprinting induced by SCNT led to the abnormalities of cloned fetuses and piglets and low cloning efficiency, and TSA rescued the disrupted imprinting in cloned embryos, fetuses and piglets, and prevented the occurrence of cloned fetus and piglet abnormalities, thereby improving the development of cloned embryos. This study would have important implications in improving cloning efficiency and the health of cloned animals.</description><subject>Aberration</subject><subject>Abnormalities</subject><subject>Animals</subject><subject>Antifungal agents</subject><subject>Cells, Cultured</subject><subject>Cloning</subject><subject>DNA methylation</subject><subject>DNA Methylation - drug effects</subject><subject>DNA Methylation - genetics</subject><subject>Efficiency</subject><subject>Embryos</subject><subject>Epigenetics</subject><subject>Female</subject><subject>Fertilization in Vitro</subject><subject>Fetuses</subject><subject>Fibroblasts - drug effects</subject><subject>Fibroblasts - metabolism</subject><subject>Gene expression</subject><subject>Genomic imprinting</subject><subject>Genomic Imprinting - drug effects</subject><subject>Genomic Imprinting - genetics</subject><subject>Health aspects</subject><subject>Histone deacetylase</subject><subject>Hogs</subject><subject>Hydroxamic Acids - pharmacology</subject><subject>Imprinting</subject><subject>Imprinting (Psychology)</subject><subject>Insulin-like growth factor II</subject><subject>Insulin-Like Growth Factor II - metabolism</subject><subject>Nuclear transfer</subject><subject>Nuclear transfer (Cloning)</subject><subject>Nuclear Transfer Techniques</subject><subject>Pregnancy</subject><subject>Somatic cell nuclear transfer</subject><subject>Suidae</subject><subject>Swine</subject><subject>Trichostatin A</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12L1DAUhoso7rr6D0QLgujFjPlo0uZGGBY_BhYWdPU2pulpJ0ubjEkq7r83dbrLVPZCetFy8pw3ed_mZNlzjNaYlvjdtRu9Vf167yysESaco_JBdooFJStOEH149H2SPQnhGiFGK84fZyeEiVQu8Wn248obvXMhqmhsvsk9BD1CyOMO8sYEP-4jNLkZ9t7YRHS5sc2oU6m-yYMbUpfONfR9bkfdg_J59MqGFnwC873pwtPsUav6AM_m91n27eOHq_PPq4vLT9vzzcVKc0HiCrO6KhhrFQWmeVFiRZCueUWgJpprjDjGpK45QwXFtKkIIyAUrkUJLYemomfZy4PuvndBzuEEiXmFcPLKWSK2B6Jx6lomQ4PyN9IpI_8WnO-k8slPD5IRwVJYlNCqLLgAwZWua8aEYkKDpknr_bzbWA_QaLDJd78QXa5Ys5Od-yWLgpSUFEngzSzg3c8UeJSDCVOQyoIbD-cui6oU07lf_YPe726mOpUMGNu6tK-eROUmRcYZ5nhKaX0PlZ4GBqPTTWpNqi8a3i4aEhPhd-zUGILcfv3y_-zl9yX7-ojdgerjLrh-jMbZsASLA6i9C8FDexcyRnIahNs05DQIch6E1Pbi-AfdNd3efPoH97oCRw</recordid><startdate>20150511</startdate><enddate>20150511</enddate><creator>Huan, Yanjun</creator><creator>Zhu, Jiang</creator><creator>Huang, Bo</creator><creator>Mu, Yanshuang</creator><creator>Kong, Qingran</creator><creator>Liu, Zhonghua</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>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150511</creationdate><title>Trichostatin A rescues the disrupted imprinting induced by somatic cell nuclear transfer in pigs</title><author>Huan, Yanjun ; Zhu, Jiang ; Huang, Bo ; Mu, Yanshuang ; Kong, Qingran ; Liu, Zhonghua</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-15b8455fa3e5c6471a20cb682eb2c6c106112bb6504313d8252e9a1b97ef6ed83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Aberration</topic><topic>Abnormalities</topic><topic>Animals</topic><topic>Antifungal agents</topic><topic>Cells, Cultured</topic><topic>Cloning</topic><topic>DNA methylation</topic><topic>DNA Methylation - drug effects</topic><topic>DNA Methylation - genetics</topic><topic>Efficiency</topic><topic>Embryos</topic><topic>Epigenetics</topic><topic>Female</topic><topic>Fertilization in Vitro</topic><topic>Fetuses</topic><topic>Fibroblasts - drug effects</topic><topic>Fibroblasts - metabolism</topic><topic>Gene expression</topic><topic>Genomic imprinting</topic><topic>Genomic Imprinting - drug effects</topic><topic>Genomic Imprinting - genetics</topic><topic>Health aspects</topic><topic>Histone deacetylase</topic><topic>Hogs</topic><topic>Hydroxamic Acids - pharmacology</topic><topic>Imprinting</topic><topic>Imprinting (Psychology)</topic><topic>Insulin-like growth factor II</topic><topic>Insulin-Like Growth Factor II - metabolism</topic><topic>Nuclear transfer</topic><topic>Nuclear transfer (Cloning)</topic><topic>Nuclear Transfer Techniques</topic><topic>Pregnancy</topic><topic>Somatic cell nuclear transfer</topic><topic>Suidae</topic><topic>Swine</topic><topic>Trichostatin A</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Huan, Yanjun</creatorcontrib><creatorcontrib>Zhu, Jiang</creatorcontrib><creatorcontrib>Huang, Bo</creatorcontrib><creatorcontrib>Mu, Yanshuang</creatorcontrib><creatorcontrib>Kong, Qingran</creatorcontrib><creatorcontrib>Liu, Zhonghua</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 - 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Academic</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>Huan, Yanjun</au><au>Zhu, Jiang</au><au>Huang, Bo</au><au>Mu, Yanshuang</au><au>Kong, Qingran</au><au>Liu, Zhonghua</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Trichostatin A rescues the disrupted imprinting induced by somatic cell nuclear transfer in pigs</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-05-11</date><risdate>2015</risdate><volume>10</volume><issue>5</issue><spage>e0126607</spage><epage>e0126607</epage><pages>e0126607-e0126607</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Imprinting disorders induced by somatic cell nuclear transfer (SCNT) usually lead to the abnormalities of cloned animals and low cloning efficiency. Histone deacetylase inhibitors have been shown to improve gene expression, genomic methylation reprogramming and the development of cloned embryos, however, the imprinting statuses in these treated embryos and during their subsequent development remain poorly studied. In this study, we investigated the dynamics of H19/Igf2 methylation and transcription in porcine cloned embryos treated with trichostatin A (TSA), and examined H19/Igf2 imprinting patterns in cloned fetuses and piglets. Our results showed that compared with the maintenance of H19/Igf2 methylation in fertilized embryos, cloned embryos displayed aberrant H19/Igf2 methylation and lower H19/Igf2 transcripts. When TSA enhanced the development of cloned embryos, the disrupted H19/Igf2 imprinting was largely rescued in these treated embryos, more similar to those detected in fertilized counterparts. Further studies displayed that TSA effectively rescued the disrupted imprinting of H19/Igf2 in cloned fetuses and piglets, prevented the occurrence of cloned fetus and piglet abnormalities, and enhanced the full-term development of cloned embryos. In conclusion, our results demonstrated that aberrant imprinting induced by SCNT led to the abnormalities of cloned fetuses and piglets and low cloning efficiency, and TSA rescued the disrupted imprinting in cloned embryos, fetuses and piglets, and prevented the occurrence of cloned fetus and piglet abnormalities, thereby improving the development of cloned embryos. This study would have important implications in improving cloning efficiency and the health of cloned animals.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25962071</pmid><doi>10.1371/journal.pone.0126607</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Aberration Abnormalities Animals Antifungal agents Cells, Cultured Cloning DNA methylation DNA Methylation - drug effects DNA Methylation - genetics Efficiency Embryos Epigenetics Female Fertilization in Vitro Fetuses Fibroblasts - drug effects Fibroblasts - metabolism Gene expression Genomic imprinting Genomic Imprinting - drug effects Genomic Imprinting - genetics Health aspects Histone deacetylase Hogs Hydroxamic Acids - pharmacology Imprinting Imprinting (Psychology) Insulin-like growth factor II Insulin-Like Growth Factor II - metabolism Nuclear transfer Nuclear transfer (Cloning) Nuclear Transfer Techniques Pregnancy Somatic cell nuclear transfer Suidae Swine Trichostatin A |
| title | Trichostatin A rescues the disrupted imprinting induced by somatic cell nuclear transfer in pigs |
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