PMID:16581799

Citation	Nadra, K, Anghel, SI, Joye, E, Tan, NS, Basu-Modak, S, Trono, D, Wahli, W and Desvergne, B (2006) Differentiation of trophoblast giant cells and their metabolic functions are dependent on peroxisome proliferator-activated receptor beta/delta. Mol. Cell. Biol. 26:3266-81
Abstract	Mutation of the nuclear receptor peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) severely affects placenta development, leading to embryonic death at embryonic day 9.5 (E9.5) to E10.5 of most, but not all, PPARbeta/delta-null mutant embryos. While very little is known at present about the pathway governed by PPARbeta/delta in the developing placenta, this paper demonstrates that the main alteration of the placenta of PPARbeta/delta-null embryos is found in the giant cell layer. PPARbeta/delta activity is in fact essential for the differentiation of the Rcho-1 cells in giant cells, as shown by the severe inhibition of differentiation once PPARbeta/delta is silenced. Conversely, exposure of Rcho-1 cells to a PPARbeta/delta agonist triggers a massive differentiation via increased expression of 3-phosphoinositide-dependent kinase 1 and integrin-linked kinase and subsequent phosphorylation of Akt. The links between PPARbeta/delta activity in giant cells and its role on Akt activity are further strengthened by the remarkable pattern of phospho-Akt expression in vivo at E9.5, specifically in the nucleus of the giant cells. In addition to this phosphatidylinositol 3-kinase/Akt main pathway, PPARbeta/delta also induced giant cell differentiation via increased expression of I-mfa, an inhibitor of Mash-2 activity. Finally, giant cell differentiation at E9.5 is accompanied by a PPARbeta/delta-dependent accumulation of lipid droplets and an increased expression of the adipose differentiation-related protein (also called adipophilin), which may participate to lipid metabolism and/or steroidogenesis. Altogether, this important role of PPARbeta/delta in placenta development and giant cell differentiation should be considered when contemplating the potency of PPARbeta/delta agonist as therapeutic agents of broad application.
Links	PubMed PMC1446964 Online version:10.1128/MCB.26.8.3266-3281.2006
Keywords	Animals; Cell Differentiation; Cell Nucleus/metabolism; Cells, Cultured; Female; Genetic Vectors; Giant Cells/metabolism; Giant Cells/physiology; Lipids/biosynthesis; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Biological; PPAR delta/genetics; PPAR delta/metabolism; PPAR-beta/genetics; PPAR-beta/metabolism; Peptides/metabolism; Phosphatidylinositol 3-Kinases/metabolism; Pregnancy; Proto-Oncogene Proteins c-akt/metabolism; Transformation, Genetic; Trophoblasts/metabolism; Trophoblasts/physiology
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