Regulation of placental matrix metalloproteinases activation of PPAR nuclear receptors

SOSA MARÍA; HIGA ROMINA; CAPOBIANCO EVANGELINA; KURTZ MELISA; WHITE VERÓNICA; JAWERBAUM ALICIA

Roma

Congreso; 41 st Annual meeting of the Diabetes and Pregnancy Study Group; 2009

European Asossiation for the Study of Diabetes. Diabetes and Pregnancy Study Group

Matrix Metalloproteinases (MMPs) are proteolytic enzymes involved in placental remodelling, functional and developmental processes, overexpressed in pro-inflammatory condition. Previous studies identified increased MMP2 and MMP9 activities in placenta from diabetic patients and experimental models. Peroxisome proliferator activated receptors (PPARs) are transcription factors activated by lipid signalling molecules such as oleic and linoleic acid and posses anti-inflammatory properties. We aim to determine whether dietary activation of PPARs regulate the activity of MMP2 and MMP9 in the placenta and serum from control and diabetic rats. Methods: Rat neonates were injected with streptozotocin (100mg/Kg) to lead to a mild diabetic model in adult rats. Control and diabetic adult females were mated and fed with a standard diet (SD) or with SD supplemented either with 6% olive oil (containing 75% oleic acid) or with 6% safflower oil (containing 75% linoleic acid) from day 0.5 of gestation. On day 13.5 of gestation, the palcentas were explanted and serum obtained for evaluation of MMP-2 and 9 activities through zimography. Results: MMP-2 and MMP-9 activities were enhanced in the palcentas from diabetic rats fed with the SD (50% and 31%, p<0.05). Both olive and sufflower oil-supplemented diets reduced palcental MMP 9 (22% and 25%, p<0.05) and MMP-2 activities (24% and 40%, p<0.05). MMP2 and MMp9 activities were also enhanced in the serum from diabetic rats fed with the SD (68% and  56%, p<0.05). The olive oil-supplemented diet reduced MMP-2 in serum from diabetic rats (55% p<0.001), while both olive and safflower oil-supplemented diets reduced MMP-9 activity in the serum from diabetic animals (70% and 58%, p<0.01). Conclusions: Overexpression of MMPs in the diabetic placenta can be prevented through dietary activation of PPARs. MMPs are also increased in serum from diabetic rats and reduced with the dietary treatments and hence, may constitute a marker of the placental pro-inflammatory state.