MCB
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nadra, K.
Right arrow Articles by Desvergne, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nadra, K.
Right arrow Articles by Desvergne, B.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, April 2006, p. 3266-3281, Vol. 26, No. 8
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.8.3266-3281.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Differentiation of Trophoblast Giant Cells and Their Metabolic Functions Are Dependent on Peroxisome Proliferator-Activated Receptor ß/{delta}

Karim Nadra,1 Silvia I. Anghel,1,2 Elisabeth Joye,1 Nguan Soon Tan,1,{dagger} Sharmila Basu-Modak,1,{ddagger} Didier Trono,2,3 Walter Wahli,1,2 and Béatrice Desvergne1,2*

Center for Integrative Genomics, University of Lausanne, CH-1015 Lausanne, Switzerland,1 National Research Center "Frontiers in Genetics",§ ,§ School of Life Sciences, Swiss Federal Institute of Technology, Lausanne, Switzerland3

Received 24 June 2005/ Returned for modification 21 July 2005/ Accepted 24 January 2006

Mutation of the nuclear receptor peroxisome proliferator-activated receptor ß/{delta} (PPARß/{delta}) severely affects placenta development, leading to embryonic death at embryonic day 9.5 (E9.5) to E10.5 of most, but not all, PPARß/{delta}-null mutant embryos. While very little is known at present about the pathway governed by PPARß/{delta} in the developing placenta, this paper demonstrates that the main alteration of the placenta of PPARß/{delta}-null embryos is found in the giant cell layer. PPARß/{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 PPARß/{delta} is silenced. Conversely, exposure of Rcho-1 cells to a PPARß/{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 PPARß/{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, PPARß/{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 PPARß/{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 PPARß/{delta} in placenta development and giant cell differentiation should be considered when contemplating the potency of PPARß/{delta} agonist as therapeutic agents of broad application.

* Corresponding author. Mailing address: Center for Integrative Genomics, University of Lausanne, CH-1015 Lausanne, Switzerland. Phone: 41 21 6924140. Fax: 41 21 6924115. E-mail: beatrice.desvergne{at}unil.ch.

{dagger} Present address: School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.

{ddagger} Present address: Department of Zoology, University of Dehli, Dehli 110007, India.

http://www.frontiers-in-genetics.org/en/index.php.

Molecular and Cellular Biology, April 2006, p. 3266-3281, Vol. 26, No. 8
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.8.3266-3281.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 2006 by the American Society for Microbiology. All rights reserved.