Dietary activation of nuclear receptor PPARdelta regulates nitric oxide and prostaglandins E2 and I2 in embryos from diabetic rats during early organogenesis.

HIGA ROMINA; WHITE VERÓNICA; CAPOBIANCO EVANGELINA; MARTÍNEZ NORA; JAWERBAUM ALICIA

Cavtat, Croacia

Congreso; 40th Annual Meeting, Diabetes and Pregnancy Study Group (DPSG), EASD.; 2008

Diabetes and Pregnancy Study Group (DPSG), EASD.

BACKGROUND: Peroxisome proliferator activated receptor d (PPARd) is a transcription factor activated by prostaglandin I2 (PGI2) and certain unsaturated fatty acids such as oleic and linoleic acids. Our previous studies have demonstrated reduced PGI2 and PPARd concentrations in embryos from diabetic mothers, and the in vitro capacity of PGI2 to regulate the embryonic concentrations of PGE2 and nitric oxide (NO), both involved in developmental processes during early organogenesis. AIM: To determine whether dietary PPARd agonists regulate embryonic concentrations of PGE2, PGI2 and NO in embryos from control and diabetic rats during early organogenesis. METHODS: Diabetes was induced by streptozotocin administration (50 mg/kg ip) to adult female rats before mating. Control  (C) and diabetic rats were fed with a standard diet (SD) or with a standard diet supplemented either with 6% olive oil (containing 75% oleic acid) or with 6% safflower oil (containing 75% linoleic acid) from days 0.5 to 10.5 of gestation.  PGI2 (by EIA), PGE2 (by RIA) and nitrates/nitrites concentrations (an index of NO production, by the griess reaction) were measured in E10.5 embryos. RESULTS: PGE2 and PGI2 levels were reduced in embryos from diabetic rats fed with standard diet (42% and 54%, p<0.05 v C). Safflower oil-supplemented diet increased PGE2 and PGI2 concentrations in embryos from control (109% and 167%, p<0.01 v SD) and diabetic rats (289% and 57%, p<0.02 vs SD). Olive oil- supplemented diet increased PGE2 levels only in embryos from diabetic rats (154% p<0.02 vs SD). Nitrates/nitrites were enhanced in embryos from diabetic rats fed with the standard diet (164% p<0.001 v C), and both olive and safflower-supplemented diets reduced their concentrations (52% and 40% reduction p<0.05 v SD). CONCLUSION: In maternal diabetes, activation of PPARd through dietary supplementation with unsaturated fatty acids prevents the embryonic anomalies in prostaglandins needed in the process of closure of the neural tube, and regulates the abnormal production of NO related with the induction of malformations during early organogenesis.