Influence of peroxisome proliferator-activated receptor {gamma} activation by its endogenous ligand 15-deoxy {Delta}12,14 prostaglandin J2 on nitric oxide production in term placental tissues from diabetic women.

JAWERBAUM ALICIA; CAPOBIANCO EVANGELINA; PUSTOVRH CAROLINA; WHITE VERÓNICA; BAIER MARIO; SALSZBERG SUSANA; PESARESI MARIO; GONZÁLEZ ELIDA

MOLECULAR HUMAN REPRODUCTION.

OXFORD UNIVERSITY PRESS

Lugar: London, UK; Año: 2004 vol. 10 p. 671 - 676

1360-9947

Diabetes induces alterations which condition placental remodelling. The levels of nitric oxide (NO) (a modulator of placental invasiveness, differentiation and proliferation) were higher in term placental explants from diabetic patients when compared to controls. Peroxisome proliferator-activated receptor gamma (PPARgamma) activation by its endogenous ligand 15-deoxy D12,14prostaglandin J2 (15dPGJ2), is a differentiating factor of adipocytes and other cell types, such as trophoblasts. 15dPGJ2 is also able to down-regulate NO production in different cell types. Our study evaluated the levels of 15dPGJ2 and PPARgamma and the influence of PPARgamma activation by 15dPGJ2 on the production of NO, in term placental tissues from control, pre-gestational and gestational diabetic patients. Our results showed that 15dPGJ2 was present in human term placenta, and that its levels were diminished in gestational (P < 0.05) and pre-gestational (P < 0.002) diabetic women when compared to controls. Exogenous 15dPGJ2 addition (2 3 1026 mol/l) down-regulated NO production in placenta from control (P < 0.001) and pre-gestational diabetic (P < 0.01) patients, but failed to do so in gestational diabetic women, whose placental PPARgamma expression was diminished in comparison to controls (P < 0.001). As the exogenous activation of PPARgamma prevented NO overproduction in placenta from pre-gestational diabetic women, it may have the potential to improve fetal outcome in this pathology.