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Publication : Stage-specific integration of maternal and embryonic peroxisome proliferator-activated receptor delta signaling is critical to pregnancy success.

First Author  Wang H Year  2007
Journal  J Biol Chem Volume  282
Issue  52 Pages  37770-82
PubMed ID  17965409 Mgi Jnum  J:128959
Mgi Id  MGI:3768326 Doi  10.1074/jbc.M706577200
Citation  Wang H, et al. (2007) Stage-specific Integration of Maternal and Embryonic Peroxisome Proliferator-activated Receptor {delta} Signaling Is Critical to Pregnancy Success. J Biol Chem 282(52):37770-37782
abstractText  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) delta plays a central role at various stages of pregnancy, whereas maternal PPARdelta is critical to implantation and decidualization, and embryonic PPARdelta is vital for placentation. Using trophoblast stem cells, we further elucidate that a reciprocal relationship between PPARdelta-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 PPARdelta signaling provides evidence that PPARdelta 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.
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