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DNA Methylation of Genes Participating in Hepatic Metabolisms and Function in Fetal Calf Liver Is Altered by Maternal Undernutrition during Gestation
This study aimed to elucidate the effects of maternal undernutrition (MUN) on epigenetic modification of hepatic genes in Japanese Black fetal calves during gestation. Using a previously established experimental design feeding the dams with 60% (LN) or 120% (HN) of their global nutritional requireme...
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| Published in: | International journal of molecular sciences 2023-06, Vol.24 (13), p.10682 |
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| creator | Muroya, Susumu Otomaru, Konosuke Oshima, Kazunaga Oshima, Ichiro Ojima, Koichi Gotoh, Takafumi |
| description | This study aimed to elucidate the effects of maternal undernutrition (MUN) on epigenetic modification of hepatic genes in Japanese Black fetal calves during gestation. Using a previously established experimental design feeding the dams with 60% (LN) or 120% (HN) of their global nutritional requirements during the 8.5-month gestational period, DNA methylation in the fetal liver was analyzed with reduced representation bisulfite sequencing (RRBS). The promoters and gene bodies in the LN fetuses were hypomethylated compared to HN fetuses. Pathway analysis showed that the genes with DMR in the exon/intron in the LN group were associated with pathways involved in Cushing syndrome, gastric acid secretion, and aldosterone synthesis and secretion. Promoter hypomethylation in the LN group was frequently observed in genes participating in various signaling pathways (thyroid hormone, Ras/Rap1, PIK3-Akt, cAMP), fatty acid metabolism, and cholesterol metabolism. The promoter hypomethylated genes
and
were upregulated in the LN group, whereas the promoter hypermethylated genes
and
were downregulated. The intron/exon hypomethylated genes
,
,
,
,
,
, and
were downregulated, whereas the hypermethylated genes
,
, and
were upregulated. Collectively, MUN alters the promoter and gene body methylation of genes associated with hepatic metabolisms (energy, cholesterol, mitochondria) and function, suggesting an impact of altered gene methylation on the dysregulation of gene expression in the fetal liver. |
| doi_str_mv | 10.3390/ijms241310682 |
| format | article |
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and
were upregulated in the LN group, whereas the promoter hypermethylated genes
and
were downregulated. The intron/exon hypomethylated genes
,
,
,
,
,
, and
were downregulated, whereas the hypermethylated genes
,
, and
were upregulated. Collectively, MUN alters the promoter and gene body methylation of genes associated with hepatic metabolisms (energy, cholesterol, mitochondria) and function, suggesting an impact of altered gene methylation on the dysregulation of gene expression in the fetal liver.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms241310682</identifier><identifier>PMID: 37445858</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>AKT protein ; Aldosterone ; Animals ; Beef ; Bisulfite ; Cattle ; Cholesterol ; Cushing syndrome ; Dam design ; Dam engineering ; Deoxyribonucleic acid ; Design of experiments ; Diabetes ; DNA ; DNA Methylation ; Down-regulation ; Epigenesis, Genetic ; Epigenetic inheritance ; Epigenetics ; Fatty acids ; Female ; Fetal Diseases ; Fetuses ; Gene expression ; Genes ; Genetic research ; Genomes ; Gestation ; Homeostasis ; Humans ; Insulin resistance ; Insulin-like growth factor II ; Insulin-like growth factor II receptors ; Insulin-like growth factors ; Lipid metabolism ; Liver ; Liver - metabolism ; Malnutrition - genetics ; Malnutrition - metabolism ; Maternal-Fetal Exchange ; Metabolic disorders ; Methylation ; Mitochondria ; Nutrients ; Nutrition ; Nutritional requirements ; Physiological aspects ; Pregnancy ; Proteins ; PTEN-induced putative kinase ; Rap1 protein ; Requirements ; RNA-Binding Proteins - metabolism ; Secretion ; Undernutrition</subject><ispartof>International journal of molecular sciences, 2023-06, Vol.24 (13), p.10682</ispartof><rights>COPYRIGHT 2023 MDPI AG</rights><rights>2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 by the authors. 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c483t-5597baf0fe08c3f7b2afd50231db54d9fb3b284555c036976ae5472f9bb37f503</citedby><cites>FETCH-LOGICAL-c483t-5597baf0fe08c3f7b2afd50231db54d9fb3b284555c036976ae5472f9bb37f503</cites><orcidid>0000-0002-9211-9740 ; 0000-0002-2376-9352</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2836457086/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2836457086?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,25731,27901,27902,36989,36990,44566,53766,53768,75096</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37445858$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Muroya, Susumu</creatorcontrib><creatorcontrib>Otomaru, Konosuke</creatorcontrib><creatorcontrib>Oshima, Kazunaga</creatorcontrib><creatorcontrib>Oshima, Ichiro</creatorcontrib><creatorcontrib>Ojima, Koichi</creatorcontrib><creatorcontrib>Gotoh, Takafumi</creatorcontrib><title>DNA Methylation of Genes Participating in Hepatic Metabolisms and Function in Fetal Calf Liver Is Altered by Maternal Undernutrition during Gestation</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>This study aimed to elucidate the effects of maternal undernutrition (MUN) on epigenetic modification of hepatic genes in Japanese Black fetal calves during gestation. Using a previously established experimental design feeding the dams with 60% (LN) or 120% (HN) of their global nutritional requirements during the 8.5-month gestational period, DNA methylation in the fetal liver was analyzed with reduced representation bisulfite sequencing (RRBS). The promoters and gene bodies in the LN fetuses were hypomethylated compared to HN fetuses. Pathway analysis showed that the genes with DMR in the exon/intron in the LN group were associated with pathways involved in Cushing syndrome, gastric acid secretion, and aldosterone synthesis and secretion. Promoter hypomethylation in the LN group was frequently observed in genes participating in various signaling pathways (thyroid hormone, Ras/Rap1, PIK3-Akt, cAMP), fatty acid metabolism, and cholesterol metabolism. The promoter hypomethylated genes
and
were upregulated in the LN group, whereas the promoter hypermethylated genes
and
were downregulated. The intron/exon hypomethylated genes
,
,
,
,
,
, and
were downregulated, whereas the hypermethylated genes
,
, and
were upregulated. Collectively, MUN alters the promoter and gene body methylation of genes associated with hepatic metabolisms (energy, cholesterol, mitochondria) and function, suggesting an impact of altered gene methylation on the dysregulation of gene expression in the fetal liver.</description><subject>AKT protein</subject><subject>Aldosterone</subject><subject>Animals</subject><subject>Beef</subject><subject>Bisulfite</subject><subject>Cattle</subject><subject>Cholesterol</subject><subject>Cushing syndrome</subject><subject>Dam design</subject><subject>Dam engineering</subject><subject>Deoxyribonucleic acid</subject><subject>Design of experiments</subject><subject>Diabetes</subject><subject>DNA</subject><subject>DNA Methylation</subject><subject>Down-regulation</subject><subject>Epigenesis, Genetic</subject><subject>Epigenetic inheritance</subject><subject>Epigenetics</subject><subject>Fatty acids</subject><subject>Female</subject><subject>Fetal Diseases</subject><subject>Fetuses</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genetic research</subject><subject>Genomes</subject><subject>Gestation</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Insulin resistance</subject><subject>Insulin-like growth factor II</subject><subject>Insulin-like growth factor II receptors</subject><subject>Insulin-like growth factors</subject><subject>Lipid metabolism</subject><subject>Liver</subject><subject>Liver - metabolism</subject><subject>Malnutrition - genetics</subject><subject>Malnutrition - metabolism</subject><subject>Maternal-Fetal Exchange</subject><subject>Metabolic disorders</subject><subject>Methylation</subject><subject>Mitochondria</subject><subject>Nutrients</subject><subject>Nutrition</subject><subject>Nutritional requirements</subject><subject>Physiological aspects</subject><subject>Pregnancy</subject><subject>Proteins</subject><subject>PTEN-induced putative kinase</subject><subject>Rap1 protein</subject><subject>Requirements</subject><subject>RNA-Binding Proteins - metabolism</subject><subject>Secretion</subject><subject>Undernutrition</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><recordid>eNptkktvEzEQgFcIRB9w5IosceGS4ufae0JRIGmlFDjQs2V77dTRrh3s3Ur5IfzfetNSGoTm4NHMN09PVb1D8IKQBn7y2z5jigiCtcAvqlNEMZ5BWPOXz_ST6iznLYSYYNa8rk4Ip5QJJk6r31--zcG1HW73nRp8DCA6sLLBZvBDpcEbvyvmsAE-gEs76WailY6dz30GKrRgOQZzCC3Msvg6sFCdA2t_ZxO4ymDeDTbZFug9uFZFDYW4CW1RxiH5Q2Q7pqnIyubh0MWb6pVTXbZvH9_z6mb59eficrb-vrpazNczQwUZZow1XCsHnYXCEMc1Vq5lZUrUakbbxmmisaCMMQNJ3fBaWUY5do3WhDsGyXn1-SHvbtS9bY0NQ1Kd3CXfq7SXUXl57An-Vm7inUSQUFSkZPj4mCHFX2PpX_Y-G9t1Ktg4ZokFEeV7GjEV-_APuo3jtI0DVVPGoaj_UhvVWemDi6WwmZLKOWeCIE6RKNTFf6gire29icE6X-xHAbOHAJNizsm6pyERlNMhyaNDKvz755t5ov9cDrkHXuvEqQ</recordid><startdate>20230626</startdate><enddate>20230626</enddate><creator>Muroya, Susumu</creator><creator>Otomaru, Konosuke</creator><creator>Oshima, Kazunaga</creator><creator>Oshima, Ichiro</creator><creator>Ojima, Koichi</creator><creator>Gotoh, Takafumi</creator><general>MDPI AG</general><general>MDPI</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-9211-9740</orcidid><orcidid>https://orcid.org/0000-0002-2376-9352</orcidid></search><sort><creationdate>20230626</creationdate><title>DNA Methylation of Genes Participating in Hepatic Metabolisms and Function in Fetal Calf Liver Is Altered by Maternal Undernutrition during Gestation</title><author>Muroya, Susumu ; Otomaru, Konosuke ; Oshima, Kazunaga ; Oshima, Ichiro ; Ojima, Koichi ; Gotoh, Takafumi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c483t-5597baf0fe08c3f7b2afd50231db54d9fb3b284555c036976ae5472f9bb37f503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>AKT protein</topic><topic>Aldosterone</topic><topic>Animals</topic><topic>Beef</topic><topic>Bisulfite</topic><topic>Cattle</topic><topic>Cholesterol</topic><topic>Cushing syndrome</topic><topic>Dam design</topic><topic>Dam engineering</topic><topic>Deoxyribonucleic acid</topic><topic>Design of experiments</topic><topic>Diabetes</topic><topic>DNA</topic><topic>DNA Methylation</topic><topic>Down-regulation</topic><topic>Epigenesis, Genetic</topic><topic>Epigenetic inheritance</topic><topic>Epigenetics</topic><topic>Fatty acids</topic><topic>Female</topic><topic>Fetal Diseases</topic><topic>Fetuses</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Genetic research</topic><topic>Genomes</topic><topic>Gestation</topic><topic>Homeostasis</topic><topic>Humans</topic><topic>Insulin resistance</topic><topic>Insulin-like growth factor II</topic><topic>Insulin-like growth factor II receptors</topic><topic>Insulin-like growth factors</topic><topic>Lipid metabolism</topic><topic>Liver</topic><topic>Liver - metabolism</topic><topic>Malnutrition - genetics</topic><topic>Malnutrition - metabolism</topic><topic>Maternal-Fetal Exchange</topic><topic>Metabolic disorders</topic><topic>Methylation</topic><topic>Mitochondria</topic><topic>Nutrients</topic><topic>Nutrition</topic><topic>Nutritional requirements</topic><topic>Physiological aspects</topic><topic>Pregnancy</topic><topic>Proteins</topic><topic>PTEN-induced putative kinase</topic><topic>Rap1 protein</topic><topic>Requirements</topic><topic>RNA-Binding Proteins - metabolism</topic><topic>Secretion</topic><topic>Undernutrition</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Muroya, Susumu</creatorcontrib><creatorcontrib>Otomaru, Konosuke</creatorcontrib><creatorcontrib>Oshima, Kazunaga</creatorcontrib><creatorcontrib>Oshima, Ichiro</creatorcontrib><creatorcontrib>Ojima, Koichi</creatorcontrib><creatorcontrib>Gotoh, Takafumi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Muroya, Susumu</au><au>Otomaru, Konosuke</au><au>Oshima, Kazunaga</au><au>Oshima, Ichiro</au><au>Ojima, Koichi</au><au>Gotoh, Takafumi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DNA Methylation of Genes Participating in Hepatic Metabolisms and Function in Fetal Calf Liver Is Altered by Maternal Undernutrition during Gestation</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2023-06-26</date><risdate>2023</risdate><volume>24</volume><issue>13</issue><spage>10682</spage><pages>10682-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>This study aimed to elucidate the effects of maternal undernutrition (MUN) on epigenetic modification of hepatic genes in Japanese Black fetal calves during gestation. Using a previously established experimental design feeding the dams with 60% (LN) or 120% (HN) of their global nutritional requirements during the 8.5-month gestational period, DNA methylation in the fetal liver was analyzed with reduced representation bisulfite sequencing (RRBS). The promoters and gene bodies in the LN fetuses were hypomethylated compared to HN fetuses. Pathway analysis showed that the genes with DMR in the exon/intron in the LN group were associated with pathways involved in Cushing syndrome, gastric acid secretion, and aldosterone synthesis and secretion. Promoter hypomethylation in the LN group was frequently observed in genes participating in various signaling pathways (thyroid hormone, Ras/Rap1, PIK3-Akt, cAMP), fatty acid metabolism, and cholesterol metabolism. The promoter hypomethylated genes
and
were upregulated in the LN group, whereas the promoter hypermethylated genes
and
were downregulated. The intron/exon hypomethylated genes
,
,
,
,
,
, and
were downregulated, whereas the hypermethylated genes
,
, and
were upregulated. Collectively, MUN alters the promoter and gene body methylation of genes associated with hepatic metabolisms (energy, cholesterol, mitochondria) and function, suggesting an impact of altered gene methylation on the dysregulation of gene expression in the fetal liver.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>37445858</pmid><doi>10.3390/ijms241310682</doi><orcidid>https://orcid.org/0000-0002-9211-9740</orcidid><orcidid>https://orcid.org/0000-0002-2376-9352</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | International journal of molecular sciences, 2023-06, Vol.24 (13), p.10682 |
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| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10341414 |
| source | Publicly Available Content Database; PubMed Central |
| subjects | AKT protein Aldosterone Animals Beef Bisulfite Cattle Cholesterol Cushing syndrome Dam design Dam engineering Deoxyribonucleic acid Design of experiments Diabetes DNA DNA Methylation Down-regulation Epigenesis, Genetic Epigenetic inheritance Epigenetics Fatty acids Female Fetal Diseases Fetuses Gene expression Genes Genetic research Genomes Gestation Homeostasis Humans Insulin resistance Insulin-like growth factor II Insulin-like growth factor II receptors Insulin-like growth factors Lipid metabolism Liver Liver - metabolism Malnutrition - genetics Malnutrition - metabolism Maternal-Fetal Exchange Metabolic disorders Methylation Mitochondria Nutrients Nutrition Nutritional requirements Physiological aspects Pregnancy Proteins PTEN-induced putative kinase Rap1 protein Requirements RNA-Binding Proteins - metabolism Secretion Undernutrition |
| title | DNA Methylation of Genes Participating in Hepatic Metabolisms and Function in Fetal Calf Liver Is Altered by Maternal Undernutrition during Gestation |
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