Expression and Potential Role of Peroxisome Proliferator-Activated Receptor γ in the Placenta of Diabetic Pregnancy

Peroxisome proliferator-activated receptor γ (PPARγ) is expressed predominantly in adipose tissue and is known to be involved in adipocyte differentiation and insulin sensitivity. Recent reports indicated that PPARγ-deficient mice were embryonic lethal due to abnormal placental development, suggesting that PPARγ plays an important role in normal development of placenta. On the other hand, expression of vascular endothelial growth factor (VEGF), the other important factor in placental development, has been demonstrated to be regulated by PPARγ in vascular smooth muscle cells. Also, diabetic pregnancy is often associated with defective placental functions. In order to investigate physiological roles of PPARγ and VEGF in placental development during diabetic pregnancy, we examined the expressions of PPARγ and VEGF in placentas, which were obtained from normal and streptozotocin-induced diabetic pregnant mouse, and studied in vitro effects of hyperglycemic condition and PPARγ ligands (rosiglitazone and 15-deoxy-delta(12,14)prostaglandin J₂) on trophoblasts using human choriocarcinoma cell lines. In diabetic mouse placentas (n = 5), expressions of PPARγ and VEGF proteins significantly increased as compared with these in normal placenta (n = 3 or 4). In vitro studies indicated that hyperglycemic condition (42 mM) significantly enhanced the PPARγ expression and hCG production, and significantly suppressed cell proliferation, however these effects were attenuated by PPARγ ligands that accompanied with increased VEGF production. These data suggest that the PPARγ pathway might be involved in the impairment of placental development induced by high glucose conditions, and that VEGF might play some roles in this pathway.