Stage-specific integration of maternal and embryonic peroxisome proliferator-activated receptor δ signaling is critical to pregnancy success

Haibin Wang, Huirong Xie, Xiaofei Sun, Susanne Tranguch, Hao Zhang, Xiangxu Jia, Dingzhi Wang, Sanjoy K. Das, Béatrice Desvergne, Walter Wahli, Raymond N. Dubois, Sudhansu K. Dey

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45 Scopus citations

Abstract

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) δ plays a central role at various stages of pregnancy, whereas maternal PPARδ is critical to implantation and decidualization, and embryonic PPARδ is vital for placentation. Using trophoblast stem cells, we further elucidate that a reciprocal relationship between PPARδ-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 PPARδ signaling provides evidence that PPARδ 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.

Original languageEnglish (US)
Pages (from-to)37770-37782
Number of pages13
JournalJournal of Biological Chemistry
Volume282
Issue number52
DOIs
StatePublished - Dec 28 2007

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Wang, H., Xie, H., Sun, X., Tranguch, S., Zhang, H., Jia, X., Wang, D., Das, S. K., Desvergne, B., Wahli, W., Dubois, R. N., & Dey, S. K. (2007). Stage-specific integration of maternal and embryonic peroxisome proliferator-activated receptor δ signaling is critical to pregnancy success. Journal of Biological Chemistry, 282(52), 37770-37782. https://doi.org/10.1074/jbc.M706577200