School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, U.K.
Biochem Soc Trans. 2013 Jun;41(3):701-9. doi: 10.1042/BST20130002.
A defining feature of mammals is the development in utero of the fetus supported by the constant flow of nutrients from the mother obtained via a specialized organ: the placenta. The placenta is also a major endocrine organ that synthesizes vast quantities of hormones and cytokines to instruct both maternal and fetal physiology. Nearly 20 years ago, David Haig and colleagues proposed that placental hormones were likely targets of the epigenetic process of genomic imprinting in response to the genetic conflicts imposed by in utero development [Haig (1993) Q. Rev. Biol. 68, 495-532]. There are two simple mechanisms through which genomic imprinting could regulate placental hormones. First, imprints could directly switch on or off alleles of specific genes. Secondly, imprinted genes could alter the expression of placental hormones by regulating the development of placental endocrine lineages. In mice, the placental hormones are synthesized in the trophoblast giant cells and spongiotrophoblast cells of the mature placenta. In the present article, I review the functional role of imprinted genes in regulating these endocrine lineages, which lends support to Haig's original hypothesis. I also discuss how imprinting defects in the placenta may adversely affect the health of the fetus and its mother during pregnancy and beyond.
哺乳动物的一个显著特征是胎儿在子宫内的发育，这得益于通过一个专门的器官——胎盘——从母体不断获得营养物质的支持。胎盘也是一个主要的内分泌器官，它合成大量的激素和细胞因子，以指导母体和胎儿的生理机能。大约 20 年前，David Haig 和同事们提出，胎盘激素可能是基因组印记这一表观遗传过程的目标，以应对子宫内发育带来的遗传冲突[Haig（1993）Q. Rev. Biol. 68, 495-532]。基因组印记可以通过两种简单的机制来调节胎盘激素。首先，印记可以直接开启或关闭特定基因的等位基因。其次，印记基因可以通过调节胎盘内分泌谱系的发育来改变胎盘激素的表达。在小鼠中，胎盘激素是在成熟胎盘的滋养层巨细胞和海绵滋养层细胞中合成的。在本文中，我回顾了印记基因在调节这些内分泌谱系中的功能作用，这为 Haig 的原始假说提供了支持。我还讨论了胎盘印记缺陷如何在怀孕期间及以后对胎儿及其母亲的健康产生不利影响。
