Regulation of placental matrix metalloproteinases activity through dietary activation of PPAR nuclear receptors

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

Roma, Italia

Congreso; 41st Annual Meeting of DPSG; 2009

Diabetes and Pregnancy Study Group (DPSG)

Background and aims: Matrix metalloproteinases (MMPs) are proteolytic enzymes involved in placental remodelling, functional and developmental processes, overexpressed in pro-inflammatory conditions.  Previous studies identified increased MMP-2 and MMP-9 activities in the 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 acids and possess anti-inflammatory properties. We aim to determine whether dietary activation of PPARs regulate the activity of MMP-2 and MMP-9 in the placenta and serum from control and diabetic rats. Methods: Rat neonates were injected with streptozotocin (100 mg/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 placentas were explanted and serum obtained for evaluation of MMP-2 and -9 activities through zymography.   Results: MMP-2 and MMP-9 activities were enhanced in the placentas from diabetic rats fed the SD (50% and 31%, p<0.05). Both olive and safflower oil-supplemented diets reduced placental MMP-9 (21% and 25%, p<0.05) and MMP-2 activities (24% and 40%, p<0.05). MMP-2 and MMP-9 activities were also enhanced in the serum from diabetic rats fed the SD (68% and 56%, p<0.01). 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.