Medical College of Wisconsin, Neonatology Suite 410, Children's Corporate Center, 999 N. 92nd Street, Wauwatosa, WI 53226, USA.
Placenta. 2012 Feb;33(2):94-9. doi: 10.1016/j.placenta.2011.11.018. Epub 2011 Dec 10.
Placental nutrient flow is the primary determinant of fetal growth. This key function of the placenta depends on several growth-promoting or -suppressing imprinted genes including Insulin-like growth factor [IGF] axis genes, which regulate nutrient transfer across the placenta. However whether changes in the placental expression of these genes parallel increased fetal growth observed in the second and third trimester remains unknown.
The aim of our study was to determine the ontogeny of key IGF axis genes and other growth regulating imprinted genes in the placenta and to characterize patterns of placental gene expression associated with intrauterine growth restriction (IUGR).
Real time RT-PCR analysis of 11 genes using specific probes were performed in the placental tissue collected at the time of delivery from 63 subjects with live birth pregnancies from 24 to 40 weeks gestation between 2009 -2010.
We found that paternally expressed gene ZNF127 (p < 0.001) was upregulated whereas IGF1 (p = 0.001) and maternally expressed gene PHLDA2 (p = 0.001) were downregulated with advancing gestational age. ROC analysis revealed a significant change in the expression of the above genes early in the third trimester. When compared to age-matched appropriate for gestational age (AGA) infants, expression of PHLDA2 (p = 0.03) IGF2R (p < 0.05) was upregulated in IUGR infants. Maternal age was also a significant predictor for IUGR (p = 0.05).
We found increased placental expression of growth-promoting imprinted genes and decreased expression of growth-suppressive imprinted genes with advancing gestational age. These changes in placental gene expression could potentially explain accelerated fetal growth seen in the third trimester. Upregulation of maternally expressed imprinted genes in IUGR population supports the "parental conflict hypothesis".
胎盘的营养物质输送是胎儿生长的主要决定因素。胎盘的这一关键功能取决于几个促进或抑制生长的印迹基因，包括胰岛素样生长因子（IGF）轴基因，这些基因调节营养物质在胎盘内的转移。然而，这些基因在胎盘中的表达变化是否与妊娠中期和晚期观察到的胎儿生长增加平行尚不清楚。
我们的研究目的是确定胎盘内关键 IGF 轴基因和其他生长调节印迹基因的个体发生，并描述与宫内生长受限（IUGR）相关的胎盘基因表达模式。
使用特定探针对 2009 年至 2010 年期间 63 名活产妊娠的胎盘组织进行实时 RT-PCR 分析，这些孕妇的妊娠时间为 24 至 40 周。
我们发现，随着胎龄的增加，父源表达基因 ZNF127（p<0.001）上调，而 IGF1（p=0.001）和母源表达基因 PHLDA2（p=0.001）下调。ROC 分析显示，这些基因的表达在妊娠晚期早期有显著变化。与胎龄匹配的适当胎龄（AGA）婴儿相比，IUGR 婴儿的 PHLDA2（p=0.03）和 IGF2R（p<0.05）表达上调。产妇年龄也是 IUGR 的一个显著预测因素（p=0.05）。
我们发现，随着胎龄的增加，促进生长的印迹基因的胎盘表达增加，而抑制生长的印迹基因的表达减少。这些胎盘基因表达的变化可能解释了妊娠晚期胎儿生长加速的现象。IUGR 人群中母源表达印迹基因的上调支持“父母冲突假说”。
