PROJECT SUMMARY/ABSTRACT
Trophoblast cell derivatives of the embryo contribute to restructuring the uterine environment, an event
required for the establishment of a successful pregnancy. The rat and human each possess a uterine-
placental interface that is characterized by deep intrauterine infiltration of trophoblast cells, which contribute to
dynamic changes in uterine immune cell, endothelial cell, smooth muscle cell, and stromal cell constituents.
This important developmental process is directed by specialized trophoblast cells possessing invasive
properties with the potential of targeting maternal cells within the uterine compartment. In the human, these
invasive trophoblast cells are referred to as extravillous trophoblast (EVT). Disruptions in differentiation of the
invasive trophoblast/EVT cell lineage, intrauterine trophoblast cell invasion, and/or trophoblast cell-directed
uterine cell modulation contribute to early pregnancy loss, placental dysfunction, pregnancy-related diseases,
and a range of postnatal health issues. The project focuses on placenta specific 1 (PLAC1), an intrinsic
regulator of placentation. Our long-term goal is to elucidate regulatory processes controlling development of
the invasive trophoblast/EVT cell lineage and its role in establishing the uterine-placental interface. In this
project, our efforts are focused on two aims. In Aim 1, we dissect the actions of PLAC1 in the establishment of
the invasive trophoblast cell lineage. In Aim 2 we investigate trophoblast cell-uterine cell crosstalk and
plasticity at the uterine-placental interface. Experimentation utilizes genetically manipulated loss-of-function rat
models, trophoblast stem cells, and genome-wide analyses of transcriptomes and chromatin landscapes.
Execution of this research project will facilitate elucidation of molecular pathways controlling trophoblast-guided
transformation of the uterine environment and will create a platform for understanding the pathogenesis of
early pregnancy loss and placental anomalies leading to pregnancy disorders.