Stage-specific Integration of Maternal and Embryonic Peroxisome Proliferator-activated Receptor Signaling Is

Successful pregnancy depends on well coordinated develop- mental events involving both maternal and embryonic compo- nents. 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, pharmaco- logical, and physiological approaches, we show here that the nuclear transcription factor peroxisome proliferator-activated receptor (PPAR) plays a central role at various stages of preg- nancy, 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 recip- rocal relationship between PPAR-AKT and leukemia inhibi- tory 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 clin- ically relevant because deferral of on time implantation leads to spontaneous pregnancy loss, and defective trophoblast invasion is one cause of preeclampsia in humans.