Roles for genomic imprinting and the zygotic genome in placental development

Abstract

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 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.

cDNA Cloning and Expression Analysis of Mest Gene in the <I>Bufo gargarizans</I>

“…ATG: initiation codon; TAG: termination codon. (Georgiades et al, 2001;Edwards et al, 2007). In the researches of huamn and mouse, imprinted role of Mest gene was related to the methylation of C P G island (Reule et al, 1998;Kosaki et al, 2000).…”

Molecular basis of imprinting disorders affecting chromosome 14: lessons from murine models

“…Skeletal muscle development is also delayed. The animals die in late gestation, probably due to placental insufficiency (Georgiades et al ,2001. mUPD12 conceptuses are extremely growth retarded from the latter third of gestation, and this is accompanied with reduced placental mass.…”

“…Robertsonian translocations have been used to generate uniparental disomic mice for this region (Cattanach et al R240 M Howard and M Charalambous 1993), and the resultant phenotypes have much in common with upd(14) syndromes (Georgiades et al ,2001.…”

“…This was associated with a narrowed capillary lumen. In the mouse, pUPD12 is associated with several placental defects in late gestation; i) defects in the cell-cell contacts between endothelial and trophoblast layers of the labyrinth, ii) abnormal behaviour of glycogen cells, causing delayed and/or shallow invasion of the maternal decidual layer (Georgiades et al 2001). Only a few cases of TS have reported placental size (Mitter et al 2006), but in these cases where there was foetal growth retardation the placenta was also small, suggesting that IUGR may have been secondary in part to placental growth restriction.…”

“…The skeletal muscle mass is disproportionately reduced-muscles have fewer and smaller myofibres, probably due to premature differentiation. The mUPD12 conceptuses die within the first few days of life, usually following respiratory failure (Georgiades et al ,2001.…”