The placenta is the first complex mammalian organ to develop and is as site of gas and nutrient exchange between the mother and fetus. The trophoblast cell is a cell type unique to the placenta and there are a variety of diverse subtypes of trophoblast cells with distinct phenotypes and functions. The work presented in this thesis investigates the expression of the cyclin dependent kinase p57kip2 (Cdkn1c) in trophoblast cells. Expression of p57kip2 has been studied in a variety of cancers and its role in the spontaneous differentiation of trophoblast stem cells to trophoblast giant cells(TGCs) has been extensively studied in vitro. In order to add to the existing literature on the role of p57 in trophoblast cell invasion, proliferation, and differentiation, we have described the early developmental expression of p57 in the placenta from embryonic day (E) 7.5 to E12.5. In these studies we show that p57 is highly expressed in the invasive trophoblast cells of the developing placenta. We also show that there is expression in the labyrinth layer of the placenta which may speak to a role of p57 not only in invasion but in the differentiation of later subtypes of TGCs. We also investigated the changes in expression of p57 in the placenta in response to maternal hypoxia. In placentas taken from E12.5 embryos, maternal hypoxia resulted in decreased Cdkn1c expression in comparison to control placentas. Placentas from male fetuses were more susceptible to these changes when compared to females. Overall maternal hypoxia also was associated with a significant decrease in expression of the giant cell marker Pl2 but not in the other markers assayed. Taken together, the work described in this thesis suggest a role for p57 in the phenotype of the invasive, early primary and secondary TGC populations. The changes in expression of Pl2 but not other TGC and labyrinth markers (Chapter2) as well as the expression seen in the labyrinth layer (Chapter 1) also suggests a role for p57 expression in the differentiation and proliferation of TGC subtypes that appear later in gestation.
Saunders, Ann Catherine E.,
"The Role of p57kip2 in Placental Development and Disease"
(2016).
Pathobiology Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://doi.org/10.7301/Z00R9MT8
