TY - JOUR
T1 - Stage-specific integration of maternal and embryonic peroxisome proliferator-activated receptor δ signaling is critical to pregnancy success
AU - Wang, Haibin
AU - Xie, Huirong
AU - Sun, Xiaofei
AU - Tranguch, Susanne
AU - Zhang, Hao
AU - Jia, Xiangxu
AU - Wang, Dingzhi
AU - Das, Sanjoy K.
AU - Desvergne, Béatrice
AU - Wahli, Walter
AU - Dubois, Raymond N.
AU - Dey, Sudhansu K.
PY - 2007/12/28
Y1 - 2007/12/28
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=38049115662&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=38049115662&partnerID=8YFLogxK
U2 - 10.1074/jbc.M706577200
DO - 10.1074/jbc.M706577200
M3 - Article
C2 - 17965409
AN - SCOPUS:38049115662
SN - 0021-9258
VL - 282
SP - 37770
EP - 37782
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 52
ER -