Altered expressions of MMP-2, MMP-9, and TIMP-2 in placentas from women exposed to lead

Experimental studies have shown that prenatal exposure to lead (Pb) produces morphological changes related to extracellular matrix remodelling. To analyse whether the matrix metalloproteinases (MMPs), particularly MMP-2, MMP-9, and the tissue inhibitor of metalloproteinases-2 (TIMP-2), are associated with morphological alterations found in placentas, the expression of these enzymes was evaluated by immunohistochemical and image analyses in placentas of women with histories of environmental exposure to Pb. The median maternal concentration of Pb in blood was 4.68 µg/dL (x = 5.85 ± 6.48 µg/dL). Significant differences related to the exposure to Pb were not detected in newborn or placenta weight. MMP-2, MMP-9, and TIMP-2 were expressed in the syncytiotrophoblast layer of placental villi. A significant increase in both MMP-2 and MMP-9 was observed in placentas of women with concentrations of Pb in blood ≥4.68 µg/dL (p = 0.01 and 0.03 for MMP-2 and MMP-9, respectively) and decrease in TIMP-2 expression (p = 0.01) resulted in a significant increase in MMP-2/TIMP-2 ratio (p < 0.01). Increased expression of MMPs may be induced to aid in repairing placental tissue damaged by the exposure to Pb and that TIMP-2 decreases its expression to permit tissue repair. Increased expression of MMPs may be important to consider as a mechanism for generating placental abnormalities and in the induction of preterm delivery or abortion.