PPARγ Regulates Trophoblast Proliferation and Promotes Labyrinthine Trilineage Differentiation

• DOI: 10.1371/journal.pone.0008055
• Publication Date: 2009-11-30T16:32:08Z
• Authors: Mana M. Parast; Heather Yu; Aleksandar Ciric; Mark W. Salata; Vannessa Davis; David S. Milstone
• Keywords: Trophoblast; Placentation; Spiral artery; Syncytiotrophoblasts

Abnormal trophoblast differentiation and function is the basis of many placenta-based pregnancy disorders, including pre-eclampsia fetal growth restriction. PPARgamma, a ligand-activated nuclear receptor, plays essential roles in placental development; null murine embryos die at midgestation due to abnormalities all layers, particular, small labyrinth expanded giant cell layer. Previous studies have focused mostly on role PPARgamma invasion. Based previously reported preadipocyte differentiation, we hypothesized that also pivotal differentiation. To test this hypothesis, report derivation wild-type PPARgamma-null stem (TS) cells.PPARgamma-null TS cells showed defects both proliferation specifically into labyrinthine trophoblast. Detailed marker analysis functional revealed reduced three lineages, enhanced particularly invasive subtypes. In addition, rosiglitazone, specific agonist, while inducing Gcm1, key regulator labyrinth. Finally, reintroducing cells, using an adenovirus, normalized invasion partially reversed defective as assessed by morphology analysis.In addition regulating invasion, predominant which, along with endothelium, form vascular exchange interface maternal blood. Elucidating cellular molecular mechanisms mediating action will help determine if modulating activity, for which clinical pharmacologic agonists already exist, might modify course disorders associated dysfunction.