Paternally expressed, imprinted insulin-like growth factor-2 in chorionic villi correlates significantly with birth weight

Fetal growth involves highly complex molecular pathways. IGF2 is a key paternally expressed growth hormone that is critical for in utero growth in mice. Its role in human fetal growth has remained ambiguous, as it has only been studied in term tissues. Conversely the maternally expressed growth supp...

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Veröffentlicht in:PloS one 2014-01, Vol.9 (1), p.e85454-e85454
Hauptverfasser: Demetriou, Charalambos, Abu-Amero, Sayeda, Thomas, Anna C, Ishida, Miho, Aggarwal, Reena, Al-Olabi, Lara, Leon, Lydia J, Stafford, Jaime L, Syngelaki, Argyro, Peebles, Donald, Nicolaides, Kypros H, Regan, Lesley, Stanier, Philip, Moore, Gudrun E
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container_volume 9
creator Demetriou, Charalambos
Abu-Amero, Sayeda
Thomas, Anna C
Ishida, Miho
Aggarwal, Reena
Al-Olabi, Lara
Leon, Lydia J
Stafford, Jaime L
Syngelaki, Argyro
Peebles, Donald
Nicolaides, Kypros H
Regan, Lesley
Stanier, Philip
Moore, Gudrun E
description Fetal growth involves highly complex molecular pathways. IGF2 is a key paternally expressed growth hormone that is critical for in utero growth in mice. Its role in human fetal growth has remained ambiguous, as it has only been studied in term tissues. Conversely the maternally expressed growth suppressor, PHLDA2, has a significant negative correlation between its term placental expression and birth weight. The aim of this study is to address the role in early gestation of expression of IGF1, IGF2, their receptors IGF1R and IGF2R, and PHLDA2 on term birth weight. Real-time quantitative PCR was used to investigate mRNA expression of IGF1, IGF2, IGF1R, IGF2R and PHLDA2 in chorionic villus samples (CVS) (n = 260) collected at 11-13 weeks' gestation. Expression was correlated with term birth weight using statistical package R including correction for several confounding factors. Transcript levels of IGF2 and IGF2R revealed a significant positive correlation with birth weight (0.009 and 0.04, respectively). No effect was observed for IGF1, IGF1R or PHLDA2 and birth weight. Critically, small for gestational age (SGA) neonates had significantly lower IGF2 levels than appropriate for gestational age neonates (p = 3.6 × 10(-7)). Our findings show that IGF2 mRNA levels at 12 weeks gestation could provide a useful predictor of future fetal growth to term, potentially predicting SGA babies. SGA babies are known to be at a higher risk for type 2 diabetes. This research reveals an imprinted, parentally driven rheostat for in utero growth.
doi_str_mv 10.1371/journal.pone.0085454
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IGF2 is a key paternally expressed growth hormone that is critical for in utero growth in mice. Its role in human fetal growth has remained ambiguous, as it has only been studied in term tissues. Conversely the maternally expressed growth suppressor, PHLDA2, has a significant negative correlation between its term placental expression and birth weight. The aim of this study is to address the role in early gestation of expression of IGF1, IGF2, their receptors IGF1R and IGF2R, and PHLDA2 on term birth weight. Real-time quantitative PCR was used to investigate mRNA expression of IGF1, IGF2, IGF1R, IGF2R and PHLDA2 in chorionic villus samples (CVS) (n = 260) collected at 11-13 weeks' gestation. Expression was correlated with term birth weight using statistical package R including correction for several confounding factors. Transcript levels of IGF2 and IGF2R revealed a significant positive correlation with birth weight (0.009 and 0.04, respectively). No effect was observed for IGF1, IGF1R or PHLDA2 and birth weight. Critically, small for gestational age (SGA) neonates had significantly lower IGF2 levels than appropriate for gestational age neonates (p = 3.6 × 10(-7)). Our findings show that IGF2 mRNA levels at 12 weeks gestation could provide a useful predictor of future fetal growth to term, potentially predicting SGA babies. SGA babies are known to be at a higher risk for type 2 diabetes. 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IGF2 is a key paternally expressed growth hormone that is critical for in utero growth in mice. Its role in human fetal growth has remained ambiguous, as it has only been studied in term tissues. Conversely the maternally expressed growth suppressor, PHLDA2, has a significant negative correlation between its term placental expression and birth weight. The aim of this study is to address the role in early gestation of expression of IGF1, IGF2, their receptors IGF1R and IGF2R, and PHLDA2 on term birth weight. Real-time quantitative PCR was used to investigate mRNA expression of IGF1, IGF2, IGF1R, IGF2R and PHLDA2 in chorionic villus samples (CVS) (n = 260) collected at 11-13 weeks' gestation. Expression was correlated with term birth weight using statistical package R including correction for several confounding factors. Transcript levels of IGF2 and IGF2R revealed a significant positive correlation with birth weight (0.009 and 0.04, respectively). 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This research reveals an imprinted, parentally driven rheostat for in utero growth.</description><subject>Age</subject><subject>Animal tissues</subject><subject>Babies</subject><subject>Base Sequence</subject><subject>Biology</subject><subject>Birth Weight</subject><subject>Childbirth &amp; labor</subject><subject>Childrens health</subject><subject>Chorionic Villi - metabolism</subject><subject>College campuses</subject><subject>Correlation</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>DNA Primers</subject><subject>Fetal development</subject><subject>Fetuses</subject><subject>Gene expression</subject><subject>Genomes</subject><subject>Genomic Imprinting</subject><subject>Gestation</subject><subject>Gestational age</subject><subject>Growth hormone</subject><subject>Growth hormones</subject><subject>Gynecology</subject><subject>Health risks</subject><subject>Humans</subject><subject>Insulin</subject><subject>Insulin resistance</subject><subject>Insulin-like growth factor I</subject><subject>Insulin-like growth factor II</subject><subject>Insulin-Like Growth Factor II - genetics</subject><subject>Insulin-like growth factor II receptors</subject><subject>Insulin-like growth factors</subject><subject>Male</subject><subject>Mathematics</subject><subject>Medicine</subject><subject>Neonates</subject><subject>Newborn babies</subject><subject>Obstetrics</subject><subject>Placenta</subject><subject>Pregnancy</subject><subject>Premature birth</subject><subject>Proteins</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Receptors</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA</subject><subject>Small for gestational age</subject><subject>Somatotropin</subject><subject>Statistical analysis</subject><subject>Statistical methods</subject><subject>Studies</subject><subject>Systematic review</subject><subject>Transcription</subject><subject>Type 2 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one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Demetriou, Charalambos</au><au>Abu-Amero, Sayeda</au><au>Thomas, Anna C</au><au>Ishida, Miho</au><au>Aggarwal, Reena</au><au>Al-Olabi, Lara</au><au>Leon, Lydia J</au><au>Stafford, Jaime L</au><au>Syngelaki, Argyro</au><au>Peebles, Donald</au><au>Nicolaides, Kypros H</au><au>Regan, Lesley</au><au>Stanier, Philip</au><au>Moore, Gudrun E</au><au>Oudejans, Cees</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Paternally expressed, imprinted insulin-like growth factor-2 in chorionic villi correlates significantly with birth weight</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-01-15</date><risdate>2014</risdate><volume>9</volume><issue>1</issue><spage>e85454</spage><epage>e85454</epage><pages>e85454-e85454</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Fetal growth involves highly complex molecular pathways. IGF2 is a key paternally expressed growth hormone that is critical for in utero growth in mice. Its role in human fetal growth has remained ambiguous, as it has only been studied in term tissues. Conversely the maternally expressed growth suppressor, PHLDA2, has a significant negative correlation between its term placental expression and birth weight. The aim of this study is to address the role in early gestation of expression of IGF1, IGF2, their receptors IGF1R and IGF2R, and PHLDA2 on term birth weight. Real-time quantitative PCR was used to investigate mRNA expression of IGF1, IGF2, IGF1R, IGF2R and PHLDA2 in chorionic villus samples (CVS) (n = 260) collected at 11-13 weeks' gestation. Expression was correlated with term birth weight using statistical package R including correction for several confounding factors. Transcript levels of IGF2 and IGF2R revealed a significant positive correlation with birth weight (0.009 and 0.04, respectively). No effect was observed for IGF1, IGF1R or PHLDA2 and birth weight. Critically, small for gestational age (SGA) neonates had significantly lower IGF2 levels than appropriate for gestational age neonates (p = 3.6 × 10(-7)). Our findings show that IGF2 mRNA levels at 12 weeks gestation could provide a useful predictor of future fetal growth to term, potentially predicting SGA babies. SGA babies are known to be at a higher risk for type 2 diabetes. This research reveals an imprinted, parentally driven rheostat for in utero growth.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24454871</pmid><doi>10.1371/journal.pone.0085454</doi><tpages>e85454</tpages><oa>free_for_read</oa></addata></record>
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source Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry
subjects Age
Animal tissues
Babies
Base Sequence
Biology
Birth Weight
Childbirth & labor
Childrens health
Chorionic Villi - metabolism
College campuses
Correlation
Diabetes
Diabetes mellitus
DNA Primers
Fetal development
Fetuses
Gene expression
Genomes
Genomic Imprinting
Gestation
Gestational age
Growth hormone
Growth hormones
Gynecology
Health risks
Humans
Insulin
Insulin resistance
Insulin-like growth factor I
Insulin-like growth factor II
Insulin-Like Growth Factor II - genetics
Insulin-like growth factor II receptors
Insulin-like growth factors
Male
Mathematics
Medicine
Neonates
Newborn babies
Obstetrics
Placenta
Pregnancy
Premature birth
Proteins
Real-Time Polymerase Chain Reaction
Receptors
Reverse Transcriptase Polymerase Chain Reaction
RNA
Small for gestational age
Somatotropin
Statistical analysis
Statistical methods
Studies
Systematic review
Transcription
Type 2 diabetes
Villus
Womens health
title Paternally expressed, imprinted insulin-like growth factor-2 in chorionic villi correlates significantly with birth weight
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