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The pleiotropic function of PPAR gamma in the placenta
W Timothy Schaiff1, Yaacov Barak, Yoel Sadovsky
1Department of Obstetrics and Gynecology, and Cell Biology and Physiology, Washington University School of Medicine, Department of OBGYN - Campus Box 8064, 4566 Scott Avenue, St. Louis, MO 63110, USA.
At different stages of placental development the cytotrophoblasts differentiate into specialized cells that are vital for specific placental tasks. These types include the invasive trophoblasts, which are responsible for invasion of the placenta into the uterine wall, and syncytiotrophoblasts, which form a barrier between the maternal and fetal circulations, govern trans-placental transport of gas, nutrient and waste, and produce placental hormones. Recent research illuminated the role of the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPAR gamma) in the areas of adipocyte and macrophage biology, insulin action, bioenergetics and inflammation. It was somewhat surprising that PPAR gamma was also found to play a pivotal role in placental biology. In this review we summarize recent data, which show that PPAR gamma is expressed in the placenta, particularly in trophoblasts, and is essential for placental development, trophoblast invasion, differentiation of cytotrophoblasts into syncytium, and regulation of fat accumulation in trophoblasts. PPAR gamma may also play a role in modulating fetal membrane signals toward parturition. The data presented here underscore the need for a focused investigation of the unique aspects of PPAR gamma function in trophoblasts, which may have direct implications for the use of PPAR gamma ligands during pregnancy.
At different stages of placental development the cytotrophoblasts differentiate into specialized cells that are vital for specific placental tasks. These types include the invasive trophoblasts, which are responsible for invasion of the placenta into the uterine wall, and syncytiotrophoblasts, which form a barrier between the maternal and fetal circulations, govern trans-placental transport of gas, nutrient and waste, and produce placental hormones. Recent research illuminated the role of the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPAR gamma) in the areas of adipocyte and macrophage biology, insulin action, bioenergetics and inflammation. It was somewhat surprising that PPAR gamma was also found to play a pivotal role in placental biology. In this review we summarize recent data, which show that PPAR gamma is expressed in the placenta, particularly in trophoblasts, and is essential for placental development, trophoblast invasion, differentiation of cytotrophoblasts into syncytium, and regulation of fat accumulation in trophoblasts. PPAR gamma may also play a role in modulating fetal membrane signals toward parturition. The data presented here underscore the need for a focused investigation of the unique aspects of PPAR gamma function in trophoblasts, which may have direct implications for the use of PPAR gamma ligands during pregnancy.
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