Expression and potential role of peroxisome proliferator-activated receptor γ in the placenta of diabetic pregnancy

Peroxisome proliferator-activated receptor gamma (PPAR gamma) is expressed predominantly in adipose tissue and is known to be involved in adipocyte differentiation and insulin sensitivity. Recent reports indicated that PPAR gamma-deficient mice were embryonic lethal due to abnormal placental development, suggesting that PPAR gamma 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 PPAR gamma in vascular smooth muscle cells. Also, diabetic pregnancy is often associated with defective placental functions. In order to investigate physiological roles of PPAR gamma and VEGF in placental development during diabetic pregnancy, we examined the expressions of PPAR gamma and VEGF in placentas, which were obtained from normal and streptozotocin-induced diabetic pregnant mouse, and studied in vitro effects of hyperglycemic condition and PPAR gamma ligands (rosiglitazone and 15-deoxy-delta(12,14)prostaglandin J(2)) on trophoblasts using human choriocarcinoma cell lines. In diabetic mouse placentas (n = 5), expressions of PPAR gimel 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 PPAR gamma expression and hCG production, and significantly suppressed cell proliferation, however these effects were attenuated by PPAR gamma ligands that accompanied with increased VEGF production. These data suggest that the PPAR gamma 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. (c) 2006 Elsevier Ltd. All rights reserved.