Influence of peroxisome proliferator-activated receptor gamma activation by its endogenous ligand 15-deoxy Delta12,14 prostaglandin J2 on nitric oxide production in term placental tissues from diabetic women.
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 Delta(12,14)prostaglandin J(2) (15dPGJ(2)), is a differentiating factor of adipocytes and other cell types, such as trophoblasts. 15dPGJ(2) is also able to down-regulate NO production in different cell types. Our study evaluated the levels of 15dPGJ(2) and PPARgamma and the influence of PPARgamma activation by 15dPGJ(2) on the production of NO, in term placental tissues from control, pre-gestational and gestational diabetic patients. Our results showed that 15dPGJ(2) 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 15dPGJ(2) addition (2 x 10(-6) 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.
Jawerbaum
A
A
Laboratory of Reproduction and Metabolism, CEFYBO-CONICET, Serrano 669, C1414DEM Buenos Aires, Argentina.
Capobianco
E
E
Pustovrh
C
C
White
V
V
Baier
M
M
Salzberg
S
S
Pesaresi
M
M
Gonzalez
E
E
D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D016640:Diabetes, Gestational / Q000378:metabolism*; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000378:metabolism*; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D009573:Nitrites / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000378:metabolism
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D007155:Immunologic Factors; D009566:Nitrates; D009573:Nitrites; D047495:PPAR gamma; D009569:Nitric Oxide; D015230:Prostaglandin D2