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Abstract:
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Preeclampsia and intrauterine growth restriction are pregnancy-related disorders. Preeclampsia, a disorder involving inappropriate placental development, is also known as toxemia or pregnancy-induced hypertension. The placenta is composed of trophoblast cells that are organized into three layers: the giant cell layer, the spongiotrophoblast layer, and the labyrinthine layer. Previous studies have shown that oxygen is an important mediator of trophoblast differentiation. Hypoxia inducible factor-1 alpha is a critical component of the cellular oxygen-sensing machinery and is essential for placental formation and embryonic survival. Preliminary data indicates that prolonged activity of HIF-1a, restricted to trophoblast cells in the mouse placenta, results in changes to placental architecture, failure of trophoblasts to remodel the maternal arteries, premature birth, and low birth weight offspring. In order to address the role of hypoxia in the intermediate spongiotrophoblast layer of the placenta, we created a lentiviral construct using a cell-specific, spongiotrophoblast-lineage promoter, Tpbpa. The first of the lentiviral constructs created for testing includes a green fluorescent protein gene driven by Tpbpa. To test hypoxia, the green fluorescent protein gene will be replaced with the HIF-1a gene. This final construct will then be used in embryo transfer studies to test oxygen sensing in the spongiotrophoblast layer of the placenta. |
