Novel Models for Studying Trophoblast Development and Placental Pathologies

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Placental development begins in the mammalian blastocyst, when the first lineage

specification event commits one cell population to making extraembryonic tissues,

including the placenta, and commits another cell population to making the embryo

proper. The mouse is an excellent animal model to study these early events and how the

resulting placenta organ supports normal fetal development and a healthy pregnancy in

the mother. The studies included in this Dissertation use the mouse to understand the role

of long non-coding RNAs during early placental development, and to create a lineage

biasing model that takes advantage of what is known about the first lineage specification

event in mammals. Using expression analysis and the CRISPR/Cas9 system to create a

knockout mouse strain, a placental-specific lncRNA was discovered and shown to be

expressed in derivatives of the ectoplacental cone. Additionally, using the line age bias

model to cause biased ablation of Hif1α in the placenta has revealed a role for fetal vs.

placental contribution of resulting phenotypes.