Roles for genomic imprinting and the zygotic genome in placental development

The placenta contains several types of fete-maternal interfaces where zygot e-derived cells interact with maternal cells or maternal blood for the prom otion of fetal growth and viability. The genetic factors regulating the int eractions between different cell types within fetomaternal interfaces and t he relative contributions of the maternal and zygotic genomes are poorly un derstood. Genomic imprinting, the epigenetic process responsible for parent al origin-dependent functional differences between homologous chromosomes, has been proposed to contribute to these events. Previous studies showed th at mouse conceptuses with an absence of imprinted differences between the t wo copies of chromosome 12 (upon paternal inheritance of both copies) die l ate in gestation and have a variety of defects, including placentomegaly. H ere we examined the role of chromosome 12 imprinting in these placentae in more detail. We show that the spatial interactions between different cell t ypes within fetomaternal interfaces are defective and identify abnormal beh aviors in both zygote-derived and maternal cells that are attributed to the genome of the zygote but not the mother. These include compromised invasio n 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 cell ular 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 effe cts. They provide insights into the function of imprinting in placental dev elopment and have evolutionary and clinical implications.