Expression and Methylation Status of Genes Regulat.. (ANGIOPLACE)
Expression and Methylation Status of Genes Regulating Placental Angiogenesis in Normal, Cloned, IVF and Monoparental Sheep Foetuses
Start date: Oct 1, 2008,
End date: Jun 30, 2012
Normal placental angiogenesis is critical for embryonic survival and development. Epigenetic modifications, such as methylation of CpG islands, regulate the expression and imprinting of genes. Epigenetic abnormalities have been observed in embryos from assisted reproductive technologies (ART), which could explain the poor placental vascularisation, embryonic/fetal death, and altered fetal growth in these pregnancies. Both cloned (somatic cell nuclear transfer, or SNCT) and monoparental (parthogenotes, only maternal genes; androgenotes, only paternal genes) embryos provide important models for studying defects in expression and methylation status/imprinting of genes regulating placental function. Our hypothesis is that placental vascular development is compromised during early pregnancy in embryos from ART, in part due to altered expression or imprinting/methylation status of specific genes regulating placental angiogenesis. We will evaluate fetal growth, placental vascular growth, and expression and epigenetic status of genes regulating placental angiogenesis during early pregnancy in 3 Specific Aims: (1) after natural mating; (2) after transfer of biparental embryos from in vitro fertilization, and SCNT; and (3) after transfer of parthenogenetic or androgenetic embryos. These studies will therefore contribute substantially to our understanding of the regulation of placental development and vascularisation during early pregnancy, and could pinpoint the mechanism contributing to embryonic loss and developmental abnormalities in foetuses from ART. Any or all of these observations will contribute to our understanding of and also our ability to successfully employ ART, which are becoming very wide spread and important in human medicine as well as in animal production.
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