The Role of PPAR-γ in Trophoblast Layer Dynamics Based on a Cell Model of Trophoblast Differentiation
Year: 2013
Type: dissertation
Abstract: Severe pre-eclampsia (sPE) is a pregnancy disorder stemming from the placenta which features abnormal trophoblast layer physiology. A transcription factor, glial cell missing-1 (GCM-1), regulates differentiation of cytotrophoblast cells into syncytiotrophoblast (SCT) within the layer. GCM-1 is regulated by PPAR-γ, a nuclear receptor controlling trophoblast differentiation in mice. We have previously shown that activation of PPAR-γ ameliorates disease features in a rat model of sPE via an upregulation of heme oxygenase-1 (HO-1), a cytoprotective enzyme. Here, we assessed how manipulating PPAR-γ influences gene expression and alters proliferation/differentiation balance in a human cell line, BeWo, which mimics SCT formation. PPAR-γ activation induced HO-1 expression and led to a transient upregulation of GCM-1 expression. Blocking PPAR-γ activity increased cell proliferation and decreased differentiation, whereas PPAR-γ stimulation did not change this balance. Since HO-1 and GCM-1 are downregulated in sPE, their upregulation via PPAR-γ offers insights into a pathway relevant to sPE management.
Source: TSpace (University of Toronto)
Author: Khrystyna Levytska
Language: English
Subfield: Obstetrics and Gynecology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2342371468