CONICET | Buscador de Institutos y Recursos Humanos

Several studies have shown that placenta does not represent an effective barrier to lead transport, which can reach the fetus and promote damage. Prenatal exposure to lead causes placental morphological changes which could involve the activity of matrix metalloproteinases (MMPs), enzymes responsible for extracellular matrix remodeling. The aim of this study was to analyze the expression and activity of MMP-2, -3 and -9 in cultures of human syncytiotrophoblast cells exposed to lead acetate and its relationship with the production of IL-1β and IL-10. Primary cultures of human syncytiotrophoblasts isolated from placentas obtained through cesarean procedure performed in women with a healthy pregnancy, were isolated using the methodology described by Kliman et al. Syncytiotrophoblasts of 48 h of culture were exposed to concentrations of 5, 10, 15, and 20 µM of lead acetate during 24 h. The expression of mRNA of MMP-2, -3, and -9 was analyzed by qRT-PCR, the MMPs collagenase activity was quantified by zymography, and the production of IL-1 and IL-10 in culture supernatants was done by immunoassay. The results showed that exposure to lead significantly decreased the expression of MMP-2 (at 15 µM), and in MMP-9 (at 15 and 20 µM), without modifying the expression of MMP-3. The decrease in the expression of MMP-9 was associated with a decrease in cytosolic gelatinolytic activity at concentrations of 10 and 20 µM and for secreted protease by 5μM of lead. No significant changes were observed in the production of IL-1β and IL-10 at any of the concentrations of Pb applied to the cultures. Notwithstanding, the trend of IL-10 suggests an inverse relationship with MMP-9 actitity. These results suggest that, in our model, lead exposure may suppress the expression and activity of MMP-9, effect that could be regulated by the presence of IL-10.