Expression of Matrix Metalloproteinase (MMP)-2 and MMP-9 in Human Placenta and Fetal Membranes in Relation to Preterm and Term Labor

Abstract

Extensive extracellular matrix (ECM) remodeling is found in many processes during human parturition at term and preterm. These include cervical ripening, fetal membrane rupture, and placental detachment from the maternal uterus. Matrix metalloproteinases (MMPs) are the main mediators of ECM degradation. The present study was designed to investigate the expression of MMP-2 and MMP-9 in human fetal membranes (FMs) and placental (PL) tissues with or without labor at preterm and term parturition. Both zymography and Western blot analysis showed that MMP-9 was significantly (P < 0.01) increased in preterm and term labor FM, compared with nonlabor. Term labor PL also had a much higher (P < 0.05) level of MMP-9 than that of term nonlabor. No significant difference in MMP-2 expression was found between labor and nonlabor tissues. Immunolocalization studies revealed a specific distribution pattern for MMP-2 and MMP-9. MMP-2 was localized to the amnion mesenchyme, chorion laeve trophoblast, decidua parietalis, and blood vessels in PL villi. MMP-9 was localized mainly to amnion epithelia, chorion laeve trophoblast, decidua parietalis, and PL syncytiotrophoblasts. Separate cell culture from different layers of FM and culture of purified PL trophoblast cells showed that PL syncytiotrophoblast and amnion epithelial cells exclusively produced MMP-9; chorion trophoblast cells secreted both MMP-2 and MMP-9, but amnion mesenchymal cells produced only MMP-2. We concluded that MMP-2 and MMP-9 exhibited cell-specific expression in the human PL. An increase in MMP-9 expression may contribute to degradation of the ECM in the FM and PL, thereby facilitating FM rupture and PL detachment from the maternal uterus at labor, both preterm and term.

Effects of Antenatal Betamethasone on Maternal and Fetoplacental Matrix Metalloproteinases 2 and 9 Activities in Human Singleton Pregnancies

“…34 In our study, we found that MMP-9 activity in the maternal serum and placenta was comparable among the groups, although a nonsignificant trend for higher levels was noted in the term group. Given that all of our patients were in active labor, this finding, as well as that of others, 35 suggests that MMP-9 is similarly up-regulated in preterm and term placenta at the time of labor and is not affected by betamethasone.…”

Circulating maternal cytokines influence fetal growth in pregnant women with rheumatoid arthritis

“…One of the main mediators of ECM degradation is metalloproteinase-9 (MMP-9)32 Overexpression of MMP-9 is suggested to contribute to ECM degradation in the fetal membrane and placenta, thereby reducing placental function and even causing fetal membrane rupture or placental detachment 33. Previous research has shown that IL-10 inhibits the expression of MMP-9 in cytotrophoblasts 34.…”

Immune cells in term and preterm labor

“…63 MMP-9 concentrations are significantly increased in the fetal membranes during labor, preterm labor and PPROM, 58,75,76,77 which directly links this enzyme to physiological ROM and pathological PPROM. Additionally, pro-inflammatory cytokines released by macrophages during labor can regulate the further release of MMPs 78 by the fetal membranes, suggesting another mechanism whereby macrophages may contribute to ROM and PPROM.…”