Georgiades P, Watkins M, Burton G J, Ferguson-Smith A C
Department of Anatomy, University of Cambridge, Downing Street, Cambridge CB2 3DY, United Kingdom.
Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4522-7. doi: 10.1073/pnas.081540898. Epub 2001 Mar 27.
The placenta contains several types of feto-maternal interfaces where zygote-derived cells interact with maternal cells or maternal blood for the promotion of fetal growth and viability. The genetic factors regulating the interactions between different cell types within feto-maternal interfaces and the relative contributions of the maternal and zygotic genomes are poorly understood. Genomic imprinting, the epigenetic process responsible for parental origin-dependent functional differences between homologous chromosomes, has been proposed to contribute to these events. Previous studies showed that mouse conceptuses with an absence of imprinted differences between the two copies of chromosome 12 (upon paternal inheritance of both copies) die late in gestation and have a variety of defects, including placentomegaly. Here we examined the role of chromosome 12 imprinting in these placentae in more detail. We show that the spatial interactions between different cell types within feto-maternal interfaces are defective and identify abnormal behaviors in both zygote-derived and maternal cells that are attributed to the genome of the zygote but not the mother. These include compromised invasion of the maternal decidualized endometrium and the central maternal artery situated within it by zygote-derived trophoblast, abnormalities in the wall of the central maternal artery, and defects within the zygote-derived cellular layer of the labyrinth, which is in direct contact with maternal blood. These findings demonstrate multiple roles for chromosome 12 imprinting in the placenta that have not previously been associated with imprinting effects. They provide insights into the function of imprinting in placental development and have evolutionary and clinical implications.
胎盘包含几种母胎界面类型，在此合子衍生细胞与母体细胞或母体血液相互作用，以促进胎儿生长和存活。目前对调节母胎界面内不同细胞类型之间相互作用的遗传因素以及母体和合子基因组的相对贡献了解甚少。基因组印记是一种负责同源染色体之间亲本来源依赖性功能差异的表观遗传过程，已被认为与这些事件有关。先前的研究表明，12号染色体的两个拷贝之间不存在印记差异的小鼠胚胎（两个拷贝均由父系遗传）在妊娠后期死亡，并出现多种缺陷，包括胎盘肿大。在这里，我们更详细地研究了12号染色体印记在这些胎盘中的作用。我们发现母胎界面内不同细胞类型之间的空间相互作用存在缺陷，并确定了合子衍生细胞和母体细胞中的异常行为，这些行为归因于合子而非母体的基因组。这些异常行为包括合子衍生的滋养层细胞对母体蜕膜化子宫内膜及其内的中央母体动脉的侵入受损、中央母体动脉壁的异常以及与母体血液直接接触的迷路合子衍生细胞层内的缺陷。这些发现证明了12号染色体印记在胎盘中具有多种作用，而这些作用以前并未与印记效应相关联。它们为印记在胎盘发育中的功能提供了见解，并具有进化和临床意义。
