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Evidence of increased hypoxia signaling in fetal liver from maternal nutrient restriction in mice
Background Intrauterine growth restriction (IUGR) is a pregnancy condition where fetal growth is reduced, and offspring from IUGR pregnancies are at increased risk for type II diabetes as adults. The liver is susceptible to fetal undernutrition experienced by IUGR infants and animal models of growth...
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| Published in: | Pediatric research 2020-02, Vol.87 (3), p.450-455 |
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| container_title | Pediatric research |
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| creator | Radford, Bethany N. Han, Victor K. M. |
| description | Background
Intrauterine growth restriction (IUGR) is a pregnancy condition where fetal growth is reduced, and offspring from IUGR pregnancies are at increased risk for type II diabetes as adults. The liver is susceptible to fetal undernutrition experienced by IUGR infants and animal models of growth restriction. This study aimed to examine hepatic expression changes in a maternal nutrient restriction (MNR) mouse model of IUGR to understand fetal adaptations that influence adult metabolism.
Methods
Liver samples of male offspring from MNR (70% of ad libitum starting at E6.5) or control pregnancies were obtained at E18.5 and differential expression was assessed by RNAseq and western blots.
Results
Forty-nine differentially expressed (FDR |
| doi_str_mv | 10.1038/s41390-019-0447-z |
| format | article |
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Intrauterine growth restriction (IUGR) is a pregnancy condition where fetal growth is reduced, and offspring from IUGR pregnancies are at increased risk for type II diabetes as adults. The liver is susceptible to fetal undernutrition experienced by IUGR infants and animal models of growth restriction. This study aimed to examine hepatic expression changes in a maternal nutrient restriction (MNR) mouse model of IUGR to understand fetal adaptations that influence adult metabolism.
Methods
Liver samples of male offspring from MNR (70% of ad libitum starting at E6.5) or control pregnancies were obtained at E18.5 and differential expression was assessed by RNAseq and western blots.
Results
Forty-nine differentially expressed (FDR < 0.1) transcripts were enriched in hypoxia-inducible pathways including Fkbp5 (1.6-fold change), Ccng2 (1.5-fold change), Pfkfb3 (1.5-fold change), Kdm3a (1.2-fold change), Btg2 (1.6-fold change), Vhl (1.3-fold change), and Hif-3a (1.3-fold change) (FDR < 0.1). Fkbp5, Pfkfb3, Kdm3a, and Hif-3a were confirmed by qPCR, but only HIF-2a (2.2-fold change,
p
= 0.002) and HIF-3a (1.3
p
= 0.03) protein were significantly increased.
Conclusion
Although a moderate impact, these data support evidence of fetal adaptation to reduced nutrients by increased hypoxia signaling in the liver.</description><identifier>ISSN: 0031-3998</identifier><identifier>EISSN: 1530-0447</identifier><identifier>DOI: 10.1038/s41390-019-0447-z</identifier><identifier>PMID: 31185486</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Adaptation, Physiological ; Animal Nutritional Physiological Phenomena ; Animals ; Animals, Newborn ; Basic Science Article ; Disease Models, Animal ; Female ; Fetal Growth Retardation - genetics ; Fetal Growth Retardation - metabolism ; Fetal Growth Retardation - physiopathology ; Fetal Hypoxia - genetics ; Fetal Hypoxia - metabolism ; Fetal Hypoxia - physiopathology ; Gene Expression Regulation, Developmental ; Gestational Age ; Hypoxia ; Liver ; Liver - growth & development ; Liver - metabolism ; Male ; Maternal Nutritional Physiological Phenomena ; Medicine ; Medicine & Public Health ; Mice ; Nutritional Status ; Pediatric Surgery ; Pediatrics ; Pregnancy ; Prenatal Exposure Delayed Effects ; Signal Transduction - genetics</subject><ispartof>Pediatric research, 2020-02, Vol.87 (3), p.450-455</ispartof><rights>International Pediatric Research Foundation, Inc 2019</rights><rights>International Pediatric Research Foundation, Inc 2019.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c415t-44b4ead865f7fd97193c45a36d9197469dcdbb3c95565d16d646f96f5f2998383</citedby><cites>FETCH-LOGICAL-c415t-44b4ead865f7fd97193c45a36d9197469dcdbb3c95565d16d646f96f5f2998383</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31185486$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Radford, Bethany N.</creatorcontrib><creatorcontrib>Han, Victor K. M.</creatorcontrib><title>Evidence of increased hypoxia signaling in fetal liver from maternal nutrient restriction in mice</title><title>Pediatric research</title><addtitle>Pediatr Res</addtitle><addtitle>Pediatr Res</addtitle><description>Background
Intrauterine growth restriction (IUGR) is a pregnancy condition where fetal growth is reduced, and offspring from IUGR pregnancies are at increased risk for type II diabetes as adults. The liver is susceptible to fetal undernutrition experienced by IUGR infants and animal models of growth restriction. This study aimed to examine hepatic expression changes in a maternal nutrient restriction (MNR) mouse model of IUGR to understand fetal adaptations that influence adult metabolism.
Methods
Liver samples of male offspring from MNR (70% of ad libitum starting at E6.5) or control pregnancies were obtained at E18.5 and differential expression was assessed by RNAseq and western blots.
Results
Forty-nine differentially expressed (FDR < 0.1) transcripts were enriched in hypoxia-inducible pathways including Fkbp5 (1.6-fold change), Ccng2 (1.5-fold change), Pfkfb3 (1.5-fold change), Kdm3a (1.2-fold change), Btg2 (1.6-fold change), Vhl (1.3-fold change), and Hif-3a (1.3-fold change) (FDR < 0.1). Fkbp5, Pfkfb3, Kdm3a, and Hif-3a were confirmed by qPCR, but only HIF-2a (2.2-fold change,
p
= 0.002) and HIF-3a (1.3
p
= 0.03) protein were significantly increased.
Conclusion
Although a moderate impact, these data support evidence of fetal adaptation to reduced nutrients by increased hypoxia signaling in the liver.</description><subject>Adaptation, Physiological</subject><subject>Animal Nutritional Physiological Phenomena</subject><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Basic Science Article</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Fetal Growth Retardation - genetics</subject><subject>Fetal Growth Retardation - metabolism</subject><subject>Fetal Growth Retardation - physiopathology</subject><subject>Fetal Hypoxia - genetics</subject><subject>Fetal Hypoxia - metabolism</subject><subject>Fetal Hypoxia - physiopathology</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Gestational Age</subject><subject>Hypoxia</subject><subject>Liver</subject><subject>Liver - growth & development</subject><subject>Liver - metabolism</subject><subject>Male</subject><subject>Maternal Nutritional Physiological Phenomena</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mice</subject><subject>Nutritional Status</subject><subject>Pediatric Surgery</subject><subject>Pediatrics</subject><subject>Pregnancy</subject><subject>Prenatal Exposure Delayed Effects</subject><subject>Signal Transduction - genetics</subject><issn>0031-3998</issn><issn>1530-0447</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp1kM1O3DAUhS3UCqZDH6CbylI3bELt-CfxEiGgSCOxgbXlsa-nRokz2MmozNPjdChISF3Z1vnOub4HoW-UnFPC2p-ZU6ZIRaiqCOdNtT9CCyoY-fv6hBaEMFoxpdoT9CXnR0IoFy0_RieM0lbwVi6QudoFB9ECHjwO0SYwGRz-_bwd_gSDc9hE04W4KRr2MJoOd2EHCfs09Lg3I6Si4ziNKUAccYJcbnYMQ5wdfbBwij5702X4-nou0cP11f3lr2p1d3N7ebGqLKdirDhfczCulcI33qmGKma5MEw6RVXDpXLWrdfMKiGkcFQ6yaVX0gtflwVZy5bo7JC7TcPTVP6h-5AtdJ2JMExZ1zWvWyobxQv64wP6OEzzIoViQrGmNCoLRQ-UTUPOCbzeptCb9Kwp0XP_-tC_LrSeG9f74vn-mjyte3Bvjn-FF6A-ALlIcQPpffT_U18Au_2Q-A</recordid><startdate>20200201</startdate><enddate>20200201</enddate><creator>Radford, Bethany N.</creator><creator>Han, Victor K. M.</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</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>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20200201</creationdate><title>Evidence of increased hypoxia signaling in fetal liver from maternal nutrient restriction in mice</title><author>Radford, Bethany N. ; Han, Victor K. M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c415t-44b4ead865f7fd97193c45a36d9197469dcdbb3c95565d16d646f96f5f2998383</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adaptation, Physiological</topic><topic>Animal Nutritional Physiological Phenomena</topic><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Basic Science Article</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Fetal Growth Retardation - genetics</topic><topic>Fetal Growth Retardation - metabolism</topic><topic>Fetal Growth Retardation - physiopathology</topic><topic>Fetal Hypoxia - genetics</topic><topic>Fetal Hypoxia - metabolism</topic><topic>Fetal Hypoxia - physiopathology</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Gestational Age</topic><topic>Hypoxia</topic><topic>Liver</topic><topic>Liver - growth & development</topic><topic>Liver - metabolism</topic><topic>Male</topic><topic>Maternal Nutritional Physiological Phenomena</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mice</topic><topic>Nutritional Status</topic><topic>Pediatric Surgery</topic><topic>Pediatrics</topic><topic>Pregnancy</topic><topic>Prenatal Exposure Delayed Effects</topic><topic>Signal Transduction - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Radford, Bethany N.</creatorcontrib><creatorcontrib>Han, Victor K. M.</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>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Public Health Database (ProQuest Medical & Health Databases)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</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>MEDLINE - Academic</collection><jtitle>Pediatric research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Radford, Bethany N.</au><au>Han, Victor K. M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evidence of increased hypoxia signaling in fetal liver from maternal nutrient restriction in mice</atitle><jtitle>Pediatric research</jtitle><stitle>Pediatr Res</stitle><addtitle>Pediatr Res</addtitle><date>2020-02-01</date><risdate>2020</risdate><volume>87</volume><issue>3</issue><spage>450</spage><epage>455</epage><pages>450-455</pages><issn>0031-3998</issn><eissn>1530-0447</eissn><abstract>Background
Intrauterine growth restriction (IUGR) is a pregnancy condition where fetal growth is reduced, and offspring from IUGR pregnancies are at increased risk for type II diabetes as adults. The liver is susceptible to fetal undernutrition experienced by IUGR infants and animal models of growth restriction. This study aimed to examine hepatic expression changes in a maternal nutrient restriction (MNR) mouse model of IUGR to understand fetal adaptations that influence adult metabolism.
Methods
Liver samples of male offspring from MNR (70% of ad libitum starting at E6.5) or control pregnancies were obtained at E18.5 and differential expression was assessed by RNAseq and western blots.
Results
Forty-nine differentially expressed (FDR < 0.1) transcripts were enriched in hypoxia-inducible pathways including Fkbp5 (1.6-fold change), Ccng2 (1.5-fold change), Pfkfb3 (1.5-fold change), Kdm3a (1.2-fold change), Btg2 (1.6-fold change), Vhl (1.3-fold change), and Hif-3a (1.3-fold change) (FDR < 0.1). Fkbp5, Pfkfb3, Kdm3a, and Hif-3a were confirmed by qPCR, but only HIF-2a (2.2-fold change,
p
= 0.002) and HIF-3a (1.3
p
= 0.03) protein were significantly increased.
Conclusion
Although a moderate impact, these data support evidence of fetal adaptation to reduced nutrients by increased hypoxia signaling in the liver.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>31185486</pmid><doi>10.1038/s41390-019-0447-z</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adaptation, Physiological Animal Nutritional Physiological Phenomena Animals Animals, Newborn Basic Science Article Disease Models, Animal Female Fetal Growth Retardation - genetics Fetal Growth Retardation - metabolism Fetal Growth Retardation - physiopathology Fetal Hypoxia - genetics Fetal Hypoxia - metabolism Fetal Hypoxia - physiopathology Gene Expression Regulation, Developmental Gestational Age Hypoxia Liver Liver - growth & development Liver - metabolism Male Maternal Nutritional Physiological Phenomena Medicine Medicine & Public Health Mice Nutritional Status Pediatric Surgery Pediatrics Pregnancy Prenatal Exposure Delayed Effects Signal Transduction - genetics |
| title | Evidence of increased hypoxia signaling in fetal liver from maternal nutrient restriction in mice |
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