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


OBJECTIVE
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.


METHODS
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.


RESULTS
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)).


CONCLUSIONS
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.
Fetal Development and Growth Research Group, Clinical and Molecular Genetics Unit, Institute of Child Health, University College London, London, United Kingdom ; Department of Obstetrics and Gynaecology, St. Mary's Campus, Imperial College London, London, United Kingdom.
Charalambos
C
Demetriou
Fetal Development and Growth Research Group, Clinical and Molecular Genetics Unit, Institute of Child Health, University College London, London, United Kingdom.
Sayeda
S
Abu-Amero
Fetal Development and Growth Research Group, Clinical and Molecular Genetics Unit, Institute of Child Health, University College London, London, United Kingdom.
Anna C
AC
Thomas
Fetal Development and Growth Research Group, Clinical and Molecular Genetics Unit, Institute of Child Health, University College London, London, United Kingdom.
Miho
M
Ishida
Institute for Women's Health, University College London, London, United Kingdom.
Reena
R
Aggarwal
Fetal Development and Growth Research Group, Clinical and Molecular Genetics Unit, Institute of Child Health, University College London, London, United Kingdom.
Lara
L
Al-Olabi
Fetal Development and Growth Research Group, Clinical and Molecular Genetics Unit, Institute of Child Health, University College London, London, United Kingdom.
Lydia J
LJ
Leon
Fetal Development and Growth Research Group, Clinical and Molecular Genetics Unit, Institute of Child Health, University College London, London, United Kingdom.
Jaime L
JL
Stafford
Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, United Kingdom.
Argyro
A
Syngelaki
Institute for Women's Health, University College London, London, United Kingdom.
Donald
D
Peebles
Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, United Kingdom.
Kypros H
KH
Nicolaides
Department of Obstetrics and Gynaecology, St. Mary's Campus, Imperial College London, London, United Kingdom.
Lesley
L
Regan
Fetal Development and Growth Research Group, Clinical and Molecular Genetics Unit, Institute of Child Health, University College London, London, United Kingdom.
Philip
P
Stanier
Fetal Development and Growth Research Group, Clinical and Molecular Genetics Unit, Institute of Child Health, University College London, London, United Kingdom.
Gudrun E
GE
Moore
D001483:Base Sequence; D001724:Birth Weight; D002824:Chorionic Villi / Q000378:metabolism*; D017931:DNA Primers; D018392:Genomic Imprinting; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008297:Male; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D007335:Insulin-Like Growth Factor II