(112) PPAR Gamma Involvement in Trophoblast Cell Differentiation and Placenta Development

Objective: To investigate the role of peroxisome proliferator-activated receptor gamma (PPARG) in invasive extravillous trophoblast (EVT) cell development and establishment of the uterine-placental interface.

Study Design: PPARG expression was evaluated in rat and human placentation sites at different time points using in situ hybridization. PPARG expression was assessed by RT-qPCR in human trophoblast stem (TS) cells in stem and EVT states. Human TS cell development was investigated following PPARG silencing with short hairpin RNAs. Global and specific cell lineages utilizing the Cre-LoxP system were used to investigate the physiology of PPARG at the placentation site and in the invasive trophoblast cell lineage of the rat placenta.

Results: PPARG transcripts were expressed in the EVT cell column and increased in abundance following differentiation of human TS cells to EVT cells. PPARG knockdown impaired human TS cell differentiation to EVT cells. In the rat, PPARG transcripts were localized primarily to trophoblast cells within the uterine-placental interface and the labyrinth zone. In addition, PPARG positive cells within the uterine-placental interface co-localized with cells expressing transcripts for Prl7b1, an invasive trophoblast cell marker. Global PPARG disruption in the rat resulted in prenatal lethality. Conditional disruption of PPARG in the invasive trophoblast cell lineage of the rat has been established and is under evaluation.

Conclusion: PPARG is a conserved driver of placentation and the invasive EVT cell lineage.