Maternal betaine supplementation during gestation modifies hippocampal expression of GR and its regulatory miRNAs in neonatal piglets
Methyl donor nutrients are critical for embryonic development of brain. Hippocampus is the most susceptible brain region to various factors including prenatal supply of methyl donors. Glucocorticoid receptor (GR) expressed in hippocampus is involved in the regulation of energy homeostasis and stress...
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Veröffentlicht in: | Journal of Veterinary Medical Science 2016, Vol.78(6), pp.921-928 |
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creator | SUN, Qinwei LI, Xi JIA, Yimin PAN, Shifeng LI, Runsheng YANG, Xiaojing ZHAO, Ruqian |
description | Methyl donor nutrients are critical for embryonic development of brain. Hippocampus is the most susceptible brain region to various factors including prenatal supply of methyl donors. Glucocorticoid receptor (GR) expressed in hippocampus is involved in the regulation of energy homeostasis and stress sensitivity. Hippocampal GR expression is highly susceptible to epigenetic regulation, yet the effect of maternal methyl donor supplementation on epigenetic regulation of GR transcription in offspring hippocampus remains unclear. In this study, we fed sows with betaine (3 g/kg) throughout the gestation and analyzed the hippocampal expression of GR mRNA and its variants, as well as the CpG methylation status of the promoter and the microRNAs predicted to target 3’ UTR of porcine GR gene in neonatal piglets. Total GR mRNA (P |
doi_str_mv | 10.1292/jvms.15-0678 |
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Hippocampus is the most susceptible brain region to various factors including prenatal supply of methyl donors. Glucocorticoid receptor (GR) expressed in hippocampus is involved in the regulation of energy homeostasis and stress sensitivity. Hippocampal GR expression is highly susceptible to epigenetic regulation, yet the effect of maternal methyl donor supplementation on epigenetic regulation of GR transcription in offspring hippocampus remains unclear. In this study, we fed sows with betaine (3 g/kg) throughout the gestation and analyzed the hippocampal expression of GR mRNA and its variants, as well as the CpG methylation status of the promoter and the microRNAs predicted to target 3’ UTR of porcine GR gene in neonatal piglets. Total GR mRNA (P<0.01) and its variants GR 1-4 (P<0.05) and 1-9,10 (P<0.01), were significantly higher in the hippocampus of betaine-treated piglets, while the content of GR protein was not significantly changed. The CpGs located in the –1650 ~ –1515 segment of GR gene were hypermethylated (P<0.05). The hippocampal expression of miR-130b (P<0.05), miR-181a (P<0.05) and miR-181d (P<0.01) was significantly up-regulated. The targeting efficacy of miR-130b and miR-181d was validated in vitro using dual-luciferase reporter assay system. Our results demonstrate that maternal betaine supplementation during gestation enhances GR mRNA expression in offspring hippocampus, which involves alterations in miRNAs expression.]]></description><identifier>ISSN: 0916-7250</identifier><identifier>EISSN: 1347-7439</identifier><identifier>DOI: 10.1292/jvms.15-0678</identifier><identifier>PMID: 26875838</identifier><language>eng</language><publisher>Japan: JAPANESE SOCIETY OF VETERINARY SCIENCE</publisher><subject>Animals ; Animals, Newborn - metabolism ; betaine ; Betaine - pharmacology ; Dietary Supplements ; Female ; Gene Expression Regulation, Developmental - drug effects ; glucocorticoid receptor ; hippocampus ; Hippocampus - drug effects ; Hippocampus - metabolism ; Hippocampus - physiology ; methylation ; MicroRNAs - biosynthesis ; MicroRNAs - physiology ; miRNA ; Physiology ; Pregnancy ; Prenatal Exposure Delayed Effects - metabolism ; Real-Time Polymerase Chain Reaction ; Receptors, Glucocorticoid - metabolism ; Receptors, Glucocorticoid - physiology ; Swine</subject><ispartof>Journal of Veterinary Medical Science, 2016, Vol.78(6), pp.921-928</ispartof><rights>2016 by the Japanese Society of Veterinary Science</rights><rights>Copyright Japan Science and Technology Agency 2016</rights><rights>2016 The Japanese Society of Veterinary Science 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c689t-858fe1a01aebd46574e344996bbe166516af0483de0cf20ba8d74ddee32e143c3</citedby><cites>FETCH-LOGICAL-c689t-858fe1a01aebd46574e344996bbe166516af0483de0cf20ba8d74ddee32e143c3</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/PMC4937150/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4937150/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,1883,4024,27923,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26875838$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SUN, Qinwei</creatorcontrib><creatorcontrib>LI, Xi</creatorcontrib><creatorcontrib>JIA, Yimin</creatorcontrib><creatorcontrib>PAN, Shifeng</creatorcontrib><creatorcontrib>LI, Runsheng</creatorcontrib><creatorcontrib>YANG, Xiaojing</creatorcontrib><creatorcontrib>ZHAO, Ruqian</creatorcontrib><title>Maternal betaine supplementation during gestation modifies hippocampal expression of GR and its regulatory miRNAs in neonatal piglets</title><title>Journal of Veterinary Medical Science</title><addtitle>J. Vet. Med. Sci.</addtitle><description><![CDATA[Methyl donor nutrients are critical for embryonic development of brain. Hippocampus is the most susceptible brain region to various factors including prenatal supply of methyl donors. Glucocorticoid receptor (GR) expressed in hippocampus is involved in the regulation of energy homeostasis and stress sensitivity. Hippocampal GR expression is highly susceptible to epigenetic regulation, yet the effect of maternal methyl donor supplementation on epigenetic regulation of GR transcription in offspring hippocampus remains unclear. In this study, we fed sows with betaine (3 g/kg) throughout the gestation and analyzed the hippocampal expression of GR mRNA and its variants, as well as the CpG methylation status of the promoter and the microRNAs predicted to target 3’ UTR of porcine GR gene in neonatal piglets. Total GR mRNA (P<0.01) and its variants GR 1-4 (P<0.05) and 1-9,10 (P<0.01), were significantly higher in the hippocampus of betaine-treated piglets, while the content of GR protein was not significantly changed. The CpGs located in the –1650 ~ –1515 segment of GR gene were hypermethylated (P<0.05). The hippocampal expression of miR-130b (P<0.05), miR-181a (P<0.05) and miR-181d (P<0.01) was significantly up-regulated. The targeting efficacy of miR-130b and miR-181d was validated in vitro using dual-luciferase reporter assay system. Our results demonstrate that maternal betaine supplementation during gestation enhances GR mRNA expression in offspring hippocampus, which involves alterations in miRNAs expression.]]></description><subject>Animals</subject><subject>Animals, Newborn - metabolism</subject><subject>betaine</subject><subject>Betaine - pharmacology</subject><subject>Dietary Supplements</subject><subject>Female</subject><subject>Gene Expression Regulation, Developmental - drug effects</subject><subject>glucocorticoid receptor</subject><subject>hippocampus</subject><subject>Hippocampus - drug effects</subject><subject>Hippocampus - metabolism</subject><subject>Hippocampus - physiology</subject><subject>methylation</subject><subject>MicroRNAs - biosynthesis</subject><subject>MicroRNAs - physiology</subject><subject>miRNA</subject><subject>Physiology</subject><subject>Pregnancy</subject><subject>Prenatal Exposure Delayed Effects - metabolism</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Receptors, Glucocorticoid - metabolism</subject><subject>Receptors, Glucocorticoid - physiology</subject><subject>Swine</subject><issn>0916-7250</issn><issn>1347-7439</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkdFr3SAUxmWsrHfd3vY8hL0urUaj5mXQlbUbdBuU7VlMcpLrJdFMTVn_gP7fNdy7ywqi4Pc739HzIfSOknNa1uXF7n6K57QqiJDqBdpQxmUhOatfog2pqShkWZFT9DrGHSEl5aJ-hU5LoWSlmNqgx-8mQXBmxA0kYx3guMzzCBO4ZJL1DndLsG7AA8TDxeQ721uIeGvn2bdmmnM1_J0DxLjqvsc3d9i4DtsUcYBhGU3y4QFP9u7HZcTWYQfemZTLZjuMkOIbdNKbMcLbw3mGfl9_-XX1tbj9efPt6vK2aIWqU6Eq1QM1hBpoOi4qyYFxXteiaYAKUVFhesIV64C0fUkaozrJuw6AlUA5a9kZ-rT3nZdmgq7Nnwxm1HOwkwkP2hurnyvObvXg7zWvmaQVyQYfDgbB_1nySPTOL-v4oqaK5FURSTP1cU-1wccYoD92oESvoek1NE0rvYaW8ff_v-oI_0spA5_3wC5nMMARMCHZdoS9m1RarNvB9Si2WxM0OPYEr2qv8w</recordid><startdate>2016</startdate><enddate>2016</enddate><creator>SUN, Qinwei</creator><creator>LI, Xi</creator><creator>JIA, Yimin</creator><creator>PAN, Shifeng</creator><creator>LI, Runsheng</creator><creator>YANG, Xiaojing</creator><creator>ZHAO, Ruqian</creator><general>JAPANESE SOCIETY OF VETERINARY SCIENCE</general><general>Japan Science and Technology Agency</general><general>The Japanese Society of Veterinary Science</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>7QR</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>2016</creationdate><title>Maternal betaine supplementation during gestation modifies hippocampal expression of GR and its regulatory miRNAs in neonatal piglets</title><author>SUN, Qinwei ; LI, Xi ; JIA, Yimin ; PAN, Shifeng ; LI, Runsheng ; YANG, Xiaojing ; ZHAO, Ruqian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c689t-858fe1a01aebd46574e344996bbe166516af0483de0cf20ba8d74ddee32e143c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Animals, Newborn - metabolism</topic><topic>betaine</topic><topic>Betaine - pharmacology</topic><topic>Dietary Supplements</topic><topic>Female</topic><topic>Gene Expression Regulation, Developmental - drug effects</topic><topic>glucocorticoid receptor</topic><topic>hippocampus</topic><topic>Hippocampus - drug effects</topic><topic>Hippocampus - metabolism</topic><topic>Hippocampus - physiology</topic><topic>methylation</topic><topic>MicroRNAs - biosynthesis</topic><topic>MicroRNAs - physiology</topic><topic>miRNA</topic><topic>Physiology</topic><topic>Pregnancy</topic><topic>Prenatal Exposure Delayed Effects - metabolism</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Receptors, Glucocorticoid - metabolism</topic><topic>Receptors, Glucocorticoid - physiology</topic><topic>Swine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SUN, Qinwei</creatorcontrib><creatorcontrib>LI, Xi</creatorcontrib><creatorcontrib>JIA, Yimin</creatorcontrib><creatorcontrib>PAN, Shifeng</creatorcontrib><creatorcontrib>LI, Runsheng</creatorcontrib><creatorcontrib>YANG, Xiaojing</creatorcontrib><creatorcontrib>ZHAO, Ruqian</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Chemoreception Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of Veterinary Medical Science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SUN, Qinwei</au><au>LI, Xi</au><au>JIA, Yimin</au><au>PAN, Shifeng</au><au>LI, Runsheng</au><au>YANG, Xiaojing</au><au>ZHAO, Ruqian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Maternal betaine supplementation during gestation modifies hippocampal expression of GR and its regulatory miRNAs in neonatal piglets</atitle><jtitle>Journal of Veterinary Medical Science</jtitle><addtitle>J. Vet. Med. Sci.</addtitle><date>2016</date><risdate>2016</risdate><volume>78</volume><issue>6</issue><spage>921</spage><epage>928</epage><pages>921-928</pages><issn>0916-7250</issn><eissn>1347-7439</eissn><abstract><![CDATA[Methyl donor nutrients are critical for embryonic development of brain. Hippocampus is the most susceptible brain region to various factors including prenatal supply of methyl donors. Glucocorticoid receptor (GR) expressed in hippocampus is involved in the regulation of energy homeostasis and stress sensitivity. Hippocampal GR expression is highly susceptible to epigenetic regulation, yet the effect of maternal methyl donor supplementation on epigenetic regulation of GR transcription in offspring hippocampus remains unclear. In this study, we fed sows with betaine (3 g/kg) throughout the gestation and analyzed the hippocampal expression of GR mRNA and its variants, as well as the CpG methylation status of the promoter and the microRNAs predicted to target 3’ UTR of porcine GR gene in neonatal piglets. Total GR mRNA (P<0.01) and its variants GR 1-4 (P<0.05) and 1-9,10 (P<0.01), were significantly higher in the hippocampus of betaine-treated piglets, while the content of GR protein was not significantly changed. The CpGs located in the –1650 ~ –1515 segment of GR gene were hypermethylated (P<0.05). The hippocampal expression of miR-130b (P<0.05), miR-181a (P<0.05) and miR-181d (P<0.01) was significantly up-regulated. The targeting efficacy of miR-130b and miR-181d was validated in vitro using dual-luciferase reporter assay system. Our results demonstrate that maternal betaine supplementation during gestation enhances GR mRNA expression in offspring hippocampus, which involves alterations in miRNAs expression.]]></abstract><cop>Japan</cop><pub>JAPANESE SOCIETY OF VETERINARY SCIENCE</pub><pmid>26875838</pmid><doi>10.1292/jvms.15-0678</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Animals, Newborn - metabolism betaine Betaine - pharmacology Dietary Supplements Female Gene Expression Regulation, Developmental - drug effects glucocorticoid receptor hippocampus Hippocampus - drug effects Hippocampus - metabolism Hippocampus - physiology methylation MicroRNAs - biosynthesis MicroRNAs - physiology miRNA Physiology Pregnancy Prenatal Exposure Delayed Effects - metabolism Real-Time Polymerase Chain Reaction Receptors, Glucocorticoid - metabolism Receptors, Glucocorticoid - physiology Swine |
title | Maternal betaine supplementation during gestation modifies hippocampal expression of GR and its regulatory miRNAs in neonatal piglets |
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