15-deoxy-Delta(12,14)-prostaglandin J(2) and peroxisome proliferator-activated receptor gamma (PPAR gamma) levels in term placental tissues from control and diabetic rats: modulatory effects of a PPAR gamma agonist on nitridergic and lipid placental metabolism

15- Deoxy- Delta (12,14)- prostaglandin J(2) ( 15dPGJ(2)) is a peroxisome proliferator- activated receptor gamma ( PPAR gamma) ligand that regulates lipid homeostasis and has anti- inflammatory properties in many cell types. We postulated that 15dPGJ(2) may regulate lipid homeostasis and nitric oxide ( NO) levels in term placental tissues and that alterations in these pathways may be involved in diabetes- induced placental derangements. In the present study, we observed that, in term placental tissues from streptozotocin- induced diabetic rats, 15dPGJ(2) concentrations were decreased ( 83%) and immunostaining for nitrotyrosine, indicating peroxynitrite- induced damage, was increased. In the presence of 15dPGJ2, concentrations of nitrates/ nitrites ( an index of NO production) were diminished ( 40%) in both control and diabetic rats, an effect that seems to be both dependent on and independent of PPAR. activation. Exogenous 15dPGJ2 did not modify lipid mass, but decreased the incorporation of C-14- acetate into triacylglycerol ( 35%), cholesteryl ester ( 55%) and phospholipid ( 32%) in placenta from control rats, an effect that appears to be dependent on PPAR. activation. In contrast, the addition of 15dPGJ(2) did not alter de novo lipid synthesis in diabetic rat placenta, which showed decreased levels of PPAR gamma. We conclude that 15dPGJ(2) modulates placental lipid metabolism and NO production. The concentration and function of 15dPGJ(2) and concentrations of PPAR. were altered in placentas from diabetic rats, anomalies probably involved in diabetes- induced placental dysfunction.