Reik Wolf, Constância Miguel, Fowden Abigail, Anderson Neil, Dean Wendy, Ferguson-Smith Anne, Tycko Benjamin, Sibley Colin
Laboratory of Developmental Genetics and Imprinting, Developmental Genetics Programme, The Babraham Institute, Cambridge CB2 4AT, UK.
J Physiol. 2003 Feb 15;547(Pt 1):35-44. doi: 10.1113/jphysiol.2002.033274. Epub 2003 Jan 24.
The placenta has evolved in eutherian mammals primarily to provide nutrients for the developing fetus. The genetic control of the regulation of supply and demand for maternal nutrients is not understood. In this review we argue that imprinted genes have central roles in controlling both the fetal demand for, and the placental supply of, maternal nutrients. Recent studies on Igf2 (insulin-like growth factor 2) knockout mouse models provide experimental support for this hypothesis. These show effects on placental transport capacity consistent with a role of IGF-II in modulating both the placental supply and fetal demand for nutrients. Imprinting of genes with such functions may have coevolved with the placenta and new evidence suggests that transporter proteins, as well as the regulators themselves, may also be imprinted. These data and hypotheses are important, as deregulation of supply and demand affects fetal growth and has long term consequences for health in mammals both in the neonatal period and, as a result of fetal programming, in adulthood.
胎盘在真兽类哺乳动物中进化主要是为发育中的胎儿提供营养。母体营养供需调节的基因控制尚不清楚。在本综述中,我们认为印记基因在控制胎儿对母体营养的需求以及胎盘对母体营养的供应方面起着核心作用。最近对Igf2(胰岛素样生长因子2)基因敲除小鼠模型的研究为这一假说提供了实验支持。这些研究显示出对胎盘转运能力的影响,这与IGF-II在调节胎盘营养供应和胎儿营养需求方面的作用一致。具有此类功能的基因印记可能与胎盘共同进化,新证据表明转运蛋白以及调节因子本身也可能是印记的。这些数据和假说很重要,因为供需失调会影响胎儿生长,并对哺乳动物的健康产生长期影响,在新生儿期如此,由于胎儿编程,在成年期也是如此。