15-deoxy-delta 12,14 prostaglandin J2 (PGJ2) modulates matriz metalloproteinases activity in the feto-placental unit of rats at midgestation.

PUSTOVRH C; CAPOBIANCO E; WHITE V; MARTÍNEZ N; HIGA R; JAWERBAUM A; GONZÁLEZ E

Santiago de Chile

Simposio; II Latin-American Symposium Materno-Fetal Interaction and Placenta: From Basic to Clinical Research (SLIMP). Internacional Federation of Placental Associations (IFPA), Placenta Association of the Americas (PAA).; 2005

SLIMP

15dPGJ2 is a peroxisome proliferator-activated receptor g (PPARg) ligand that regulates metabolic homeostasis and inhibits the expression and activity of proinflammatory mediators. 15dPGJ2 is also associated with a reduction of MMPs expression and activity in many cell types. We have previously found that maternal diabetes increases MMPs activities in the feto-placetal unit. The aim of the present work was to evaluate the production of 15dPGJ2 and its capacity to regulate MMPs levels in placenta and fetuses from control (C) and neonatal-streptozotocin-induced diabetic (D) rats at midgestation. Methods: placental and fetal 15dPGJ2 levels were quantified by EIA. Fetuses and placenta (day 13.5 of gestation) were incubated for 1 h either with or without 15dPGJ2 additions (2 mM). Fetal MMP2 levels and activity and placental MMP2 and MMP9 levels and activities were evaluated by immunohistochemistry and zymography. Our results showed that in C and D placenta, 15dPGJ2 reduced the levels of MMP9 (p<0.05) and MMP2 (p<0.05) in both their proenzyme and active forms. In D fetuses, 15dPGJ2 also reduced the enhanced MMP2 levels and activity (p<0.05). In the D group, the levels of 15dPGJ2 were decreased in both placenta and fetuses (93%, p<0.01 and 71%, p<0.05 respectively) when compared to C. We conclude that 15dPGJ2 negatively regulates MMPs levels in the feto-placental unit at midgestation. The overproduction of placental and fetal MMPs in the D group is likely to be influenced by the altered production of 15dPGJ2 and may be involved in diabetes-induced placental dysfunction and fetal anomalies. Supported by FONCYT PICT 05 10652 (Argentina).