HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 52, 37770-37782, December 28, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/52/37770    most recent M706577200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, H. Articles by Dey, S. K. Search for Related Content PubMed PubMed Citation Articles by Wang, H. Articles by Dey, S. K. Social Bookmarking                      What's this?

Stage-specific Integration of Maternal and Embryonic Peroxisome Proliferator-activated Receptor Signaling Is Critical to Pregnancy Success^*

Haibin Wang¹², Huirong Xie¹³, Xiaofei Sun, Susanne Tranguch^¶4, Hao Zhang, Xiangxu Jia, Dingzhi Wang^||, Sanjoy K. Das^**, Béatrice Desvergne, Walter Wahli, Raymond N. DuBois^¶||, and Sudhansu K. Dey^¶5

From the Departments of Pediatrics, Pharmacology, ^¶Cell and Developmental Biology, ^||Medicine, and ^**Cancer Biology, Division of Reproductive and Developmental Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232 and Center for Integrative Genomics, University of Lausanne, CH-1015 Lausanne, Switzerland

Successful pregnancy depends on well coordinated developmental events involving both maternal and embryonic components. Although a host of signaling pathways participate in implantation, decidualization, and placentation, whether there is a common molecular link that coordinates these processes remains unknown. By exploiting genetic, molecular, pharmacological, and physiological approaches, we show here that the nuclear transcription factor peroxisome proliferator-activated receptor (PPAR) plays a central role at various stages of pregnancy, whereas maternal PPAR is critical to implantation and decidualization, and embryonic PPAR is vital for placentation. Using trophoblast stem cells, we further elucidate that a reciprocal relationship between PPAR-AKT and leukemia inhibitory factor-STAT3 signaling pathways serves as a cell lineage sensor to direct trophoblast cell fates during placentation. This novel finding of stage-specific integration of maternal and embryonic PPAR signaling provides evidence that PPAR is a molecular link that coordinates implantation, decidualization, and placentation crucial to pregnancy success. This study is clinically relevant because deferral of on time implantation leads to spontaneous pregnancy loss, and defective trophoblast invasion is one cause of preeclampsia in humans.

Received for publication, August 8, 2007 , and in revised form, September 21, 2007.

^* This work was supported in part by National Institutes of Health Grants HD12304, DA06668, P01-CA-77839 (to S. K. Dey), ES07814, HD37830 (to S. K. Das), and HD050315 (to H. W.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1 and S2.

¹ Both authors contributed equally to this work.

² Recipient of support from The Turner Foundation.

³ A Lalor Foundation postdoctoral fellow.

⁴ Supported by National Research Service Award Individual Fellowship F31 DA021062 [GenBank] from the National Institute on Drug Abuse.

⁵ Recipient of MERIT Awards from the NICHD, National Institutes of Health, and National Institute on Drug Abuse. To whom correspondence should be addressed. Tel.: 615-322-8642; E-mail: sk.dey{at}vanderbilt.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C. Gillio-Meina, S. H. Phang, J. P Mather, B. S Knight, and T. G Kennedy Expression patterns and role of prostaglandin-endoperoxide synthases, prostaglandin E synthases, prostacyclin synthase, prostacyclin receptor, peroxisome proliferator-activated receptor delta and retinoid x receptor alpha in rat endometrium during artificially-induced decidualization Reproduction, March 1, 2009; 137(3): 537 - 552. [Abstract] [Full Text] [PDF]

				Y. Hirota, S. Tranguch, T. Daikoku, A. Hasegawa, Y. Osuga, Y. Taketani, and S. K. Dey Deficiency of Immunophilin FKBP52 Promotes Endometriosis Am. J. Pathol., December 1, 2008; 173(6): 1747 - 1757. [Abstract] [Full Text] [PDF]