Fowden A L, Sibley C, Reik W, Constancia M
Department of Physiology, Cambridge, UK.
Horm Res. 2006;65 Suppl 3:50-8. doi: 10.1159/000091506. Epub 2006 Apr 10.
In mammals, imprinted genes have an important role in feto-placental development. They affect the growth, morphology and nutrient transfer capacity of the placenta and, thereby, control the nutrient supply for fetal growth. In particular, the reciprocally imprinted Igf2-H19 gene complex has a central role in these processes and matches the placental nutrient supply to the fetal nutrient demands for growth. Comparison of Igf2P0 and complete Igf2 null mice has shown that interplay between placental and fetal Igf2 regulates both placental growth and nutrient transporter abundance. In turn, epigenetic modification of imprinted genes via changes in DNA methylation may provide a mechanism linking environmental cues to placental phenotype, with consequences for development both before and after birth. Changes in expression of imprinted genes, therefore, have major implications for developmental programming and may explain the poor prognosis of the infant born small for gestational age and the wide spectrum of adult-onset diseases that originate in utero.
在哺乳动物中，印记基因在胎儿-胎盘发育中发挥着重要作用。它们影响胎盘的生长、形态和营养物质转运能力，从而控制胎儿生长所需的营养供应。特别是，相互印记的Igf2-H19基因复合体在这些过程中起着核心作用，并使胎盘营养供应与胎儿生长的营养需求相匹配。Igf2P0小鼠和完全缺失Igf2基因的小鼠的比较表明，胎盘和胎儿Igf2之间的相互作用调节着胎盘的生长和营养转运蛋白的丰度。反过来，通过DNA甲基化变化对印记基因进行表观遗传修饰，可能提供一种将环境线索与胎盘表型联系起来的机制，对出生前后的发育都会产生影响。因此，印记基因表达的变化对发育编程具有重大影响，可能解释了小于胎龄儿预后不良以及源于子宫内的多种成人期疾病。
