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

Peroxisome proliferator-activated receptor gamma (PPARgamma) is expressed predominantly in adipose tissue and is known to be involved in adipocyte differentiation and insulin sensitivity. Recent reports indicated that PPARgamma-deficient mice were embryonic lethal due to abnormal placental development, suggesting that PPARgamma 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 PPARgamma in vascular smooth muscle cells. Also, diabetic pregnancy is often associated with defective placental functions. In order to investigate physiological roles of PPARgamma and VEGF in placental development during diabetic pregnancy, we examined the expressions of PPARgamma and VEGF in placentas, which were obtained from normal and streptozotocin-induced diabetic pregnant mouse, and studied in vitro effects of hyperglycemic condition and PPARgamma 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 PPARgamma 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 PPARgamma expression and hCG production, and significantly suppressed cell proliferation, however these effects were attenuated by PPARgamma ligands that accompanied with increased VEGF production. These data suggest that the PPARgamma 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.