Roles for genomic imprinting and the zygotic genome in placental development
Roles for genomic imprinting and the zygotic genome in placental development
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DOI：
10.1073/pnas.081540898
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发表时间：
2001-04-10
影响因子：
11.1
通讯作者：
Ferguson-Smith, AC
中科院分区：
文献类型：
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作者：
Georgiades, P;Watkins, M;Ferguson-Smith, AC
胎盘包含几种类型的胎儿-母体界面，其中受精卵衍生的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。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知之甚少。基因组印记，表观遗传过程负责亲本来源依赖的同源染色体之间的功能差异，已被提出有助于这些事件。先前的研究表明，在12号染色体的两个拷贝之间缺乏印记差异的小鼠概念（在两个拷贝的父系遗传下）在妊娠后期死亡，并具有各种缺陷，包括胎盘肥大。在这里，我们研究了12号染色体印迹在这些胎盘中的作用更详细。我们发现，不同细胞类型之间的空间相互作用的母胎界面是有缺陷的，并确定异常行为的受精卵衍生和母体细胞，这是由于受精卵的基因组，但不是母亲。这些包括受精卵来源的滋养层对母体蜕膜化子宫内膜和位于其中的母体中央动脉的损害性侵入，母体中央动脉壁的异常，以及与母体血液直接接触的迷路的受精卵来源的细胞层内的缺陷。这些发现证明了胎盘中12号染色体印记的多种作用，这些作用之前并未与印记效应相关。他们提供了深入了解印记在胎盘发育中的功能，并具有进化和临床意义。
The placenta contains several types of fete-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 fetomaternal 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 fetomaternal 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.