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.
Fetal Development and Growth Research Group, Clinical and Molecular Genetics Unit, Institute of Child Health, University College London, London, United Kingdom.
PLoS One. 2014 Jan 15;9(1):e85454. doi: 10.1371/journal.pone.0085454. eCollection 2014.
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.
胎儿生长涉及高度复杂的分子途径。IGF2 是一种关键的父系表达生长激素，对小鼠宫内生长至关重要。其在人类胎儿生长中的作用一直存在争议，因为它仅在足月组织中进行了研究。相反，母系表达的生长抑制剂 PHLDA2 与其在足月胎盘的表达和出生体重之间存在显著的负相关。
本研究旨在探讨 IGF1、IGF2、其受体 IGF1R 和 IGF2R 以及 PHLDA2 在妊娠早期的表达与足月出生体重的关系。
使用实时定量 PCR 技术检测 11-13 周妊娠的绒毛膜绒毛样本（CVS）（n = 260）中 IGF1、IGF2、IGF1R、IGF2R 和 PHLDA2 的 mRNA 表达。使用统计软件包 R 分析表达与足月出生体重的相关性，包括对多个混杂因素进行校正。
IGF2 和 IGF2R 的转录水平与出生体重呈显著正相关（分别为 0.009 和 0.04）。IGF1、IGF1R 或 PHLDA2 与出生体重无相关性。重要的是，小于胎龄儿（SGA）新生儿的 IGF2 水平明显低于适于胎龄儿（p = 3.6 × 10(-7)）。
我们的研究结果表明，妊娠 12 周时 IGF2 mRNA 水平可作为预测未来胎儿足月生长的有用指标，可能预测 SGA 婴儿。已知 SGA 婴儿患 2 型糖尿病的风险更高。本研究揭示了一种印迹的、父母驱动的宫内生长变阻器。
