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Examining the effects of oxygen tension on extravillous trophoblast column outgrowth during the first trimester of pregnancy Treissman, Jenna Elizabeth


Oxygen tension is thought to regulate many of the cellular and molecular processes that contribute to placenta development. An area of recent focus has been on the importance of a low-oxygen environment in controlling progenitor trophoblast differentiation along the invasive extravillous pathway. However, previously published research on the role of oxygen in trophoblast differentiation is conflicting. In this thesis, the effects of low (1%), physiologically normal (5%) and high (20%) oxygen conditions on extravillous trophoblast differentiation and column formation are examined using a human placental explant model. I show that culture in low oxygen conditions enhances column outgrowth and promotes the expression of pro-extravillous genes and gene pathways. By contrast, culture in high oxygen conditions promotes trophoblast proliferation, reduces column outgrowth and stalls differentiation along the extravillous pathway. I show that both low and physiologically normal oxygen conditions increase expression of the lysyl oxidase gene, and that this gene plays an important role in promoting extravillous column outgrowth. Together, these findings support hypoxia as an important factor driving trophoblast differentiation along the extravillous pathway. Additionally, this work provides new insight into specific molecular processes, regulated by oxygen tension, that may play an important role in early placentation.

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