Thomas Brown (Advisor), Courtney Sulentic (Committee Member), Christopher Wyatt (Committee Member)
Master of Science (MS)
Hypoxia-inducible factor-1 alpha (HIF-1a) is a critical component of the cellular oxygen-sensing machinery and is essential for placental formation and embryonic survival. In this study, we promoted prolonged expression of HIF-1a, by using a form that is insensitive to oxygen, denoted as CA-HIF-1a. In order to have continual placental specific expression of the CA-HIF-1a, lentiviral infection was performed on embryos at the blastocyst stage of development and transferred into pseudo-pregnant mothers. Placental analysis was performed via in situ hybridization on embryonic day 14.5 (E14.5) to determine the effects of CA-HIF-1a prolonged expression. Data indicate that prolonged activity of CA-HIF-1a restricted to trophoblast cells in the mouse placenta results in the inability of cells to advance from their progenitor states, failure of the placenta to organize properly, and failure of trophoblasts to remodel the maternal arteries. Since HIF-1a has the ability to cause developmental placental disruption, its regulation in the placenta could be key in multiple pregnancy-associated disorders such as pre-eclampsia and intrauterine growth restriction (IUGR).
Department or Program
Microbiology and Immunology
Year Degree Awarded
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