CEFYBO   02669
CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Dietary PPAR agonists prevent matrix metalloproteinases overactivity in embryos and decidua from diabetic rats.
Autor/es:
HIGA R; WHITE V; MARTÍNEZ N; SOSA M; JAWERBAUM A
Lugar:
Santiago de Chile, Chile
Reunión:
Congreso; 6th World Congress on Developmental Origins of Health and Disease; 2009
Institución organizadora:
Developmental Origins of Health and Disease (DOHaD)
Resumen:
Maternal diabetes is a pathology related to embryo malformations and embryo-placental metabolic disorders. Remodelling of the extracellular matrix (ECM) accompanies the changes in embryonic and uterine tissues that occur during development. Alterations in ECM components have been found in placentas and embryonic tissues from diabetic rats and are related to disturbances in the activity of matrix metalloproteinases (MMPs), enzymes involved in ECM degradation. Our previous works have shown that MMP2 and MMP9 are increased in fetuses and placentas in experimental models of diabetes. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that modulate the expression of genes involved in lipid metabolism, glucose homeostasis and developmental processes. PPAR activators are lipid molecules such as oleic and linoleic acids, present in high concentrations in olive and safflower oils respectively. Objective: To analyse the capability of dietary supplementation with either 6% olive oil or 6% safflower oil to regulate MMPs activity in embryos and decidua from control and diabetic rats during early organogenesis, a period characterized with a significant remodelling of the decidua and in which most embryo malformations are induced. Methods: Diabetes was induced by streptozotocin administration (50 mg/kg) to adult rats. From day 0.5 to 10.5 of gestation, control and diabetic rats were fed ad libitum with: a standard diet (commercial rat chow) or with a standard diet supplemented with 6% olive oil or with 6% safflower oil. At day 10.5 of gestation decidual tissues and embryos were explanted and used for morphological analysis or stored at -80°C for experimental procedures. Activity of embryonic and decidual MMP2 and MMP9 and their proenzymes (proMMP2 and proMMP9) was evaluated by zymography and the results were expressed as arbitrary units. Results: We found that diabetic rats have increased embryo resorptions (35.9%, P<0.001) and malformations (14.2%, P<0.001) when compared to controls (6.5% and 1.9% respectively). Both olive oil and safflower oil-supplemented diets were capable of reducing resorptions (10.3% and 12.1% respectively, P<0.001) and malformations (6.4% and 7.1% respectively, P<0.05) in diabetic rats. Embryos from diabetic rats showed increased activity of MMP9 (4.0±0.6, P<0.001), proMMP2 (5.4±0.6, P<0.05) and MMP2 (3.8±0.6, P<0.05) when compared to embryos from control rats (1.0±0.2, 3.4±0.4 and 2.0±0.5 respectively). Both olive and safflower oil-supplemented diets diminished the overactivity of MMP9 (1.4±0.2 and 1.9±0.4 respectively, P<0.05), proMMP2 (3.5±0.2 and 3.5±0.3 respectively, P<0.05) and MMP2 (2.0±0.2 and 1.7±0.2 respectively, P<0.05) in embryos from diabetic rats. Decidua from diabetic rats showed enhanced activity of MMP9 (2.1±0.2, P<0.001) and proMMP2 (2.9±0.3, P<0.001) when compared to controls (1.0±0.1 and 1.4±0.1 respectively). The olive oil (1.1±0.2, P<0.01) and safflower oil-supplemented diets (1.5±0.1, P<0.05) prevented the MMP9 overactivity in diabetic decidua. Conclusions: Maternal diabetes induces increased rates of resorptions and malformations, probably related to the enhanced activation of MMP9 and MMP2 that lead to an abnormal remodelling during embryo and decidua development. Both olive and safflower oil-supplemented diets, enriched in PPAR activators, are able to diminish the resorption and malformation rates and to prevent the overactivation of MMPs induced by maternal diabetes.