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Changes in Matrix Metalloproteinase 2 Activities in Amniochorions During Premature Rupture of Membranes

Department of Obstetrics and Gynecology and Host Defense and Biochemical Research, Juntendo University School of Medicine, Tokyo, Japan oota3017{at}yahoo.co.jp

Hisashi Yonemoto, MD

Akimasa Someya, PhD

Shigeru Itoh, MD

Katsuyuki Kinoshita, MD

Isao Nagaoka, MD

Department of Obstetrics and Gynecology and Host Defense and Biochemical Research, Juntendo University School of Medicine, Tokyo, Japan

Objective: Increased proteolytic activities of matrix metalloproteinases (MMPs) such as MMP-3 and MMP-9 are associated with premature rupture of membranes et term. However, it is unclear whether MMP-2 is involved in the premature rupture of membranes. In this study, to elucidate the role of MMP-2, we evaluated the activity of MMP-2 and also the expression of pro-MMP-2, membrane type 1 (MT1)-MMP and tissue inhibitor of metalloproteinase (TIMP)-1 in premature rupture of membranes.

Methods: Amniochrions were prepared from 29 subjects with no labor (cesarean section; CS, n = 10), labor (normal delivery; ND, n = 10), and labor during premature rupture of membranes (PROM, n = 9). MMP-2 activity was spectrophotometrically assayed by measuring the digestion of an MMP-2-specific substrate. The levels of pro-MMP-2, MT1-MMMP and TIME-1 were determined by Western immunoblotting.

Results: The activity of MMP-2 in PROM was significantly higher than that in CS and ND (P <.05). In addition, the levels of MT1-MMP, an activator of MMP-2, were higher in PROM than in CS and ND. In contrast, the level of TIMP-1, an inhibitor of MMP-2 was substantially lower in PROM than CS and ND. Moreover, the levels of pro-MMP-2 were increased more significantly in PROM and ND than in CS (P <.05).

Conclusion: Our results suggest that the increased expression of pro-MMP-2 and MT1-MMP and decreased expression of TIMP-1 may result in the increased activity of MMP-2, which is involved in the degradation of extracellular matrix (ECM) of fetal membrane, thereby inducing the premature rupture of membranes at term.

Key Words: Matrix metalloproteinase • MMP-2 • MT1-MMP • TIMP-1 • PROM

Journal of the Society for Gynecologic Investigation, Vol. 13, No. 8, 592-597 (2006)
DOI: 10.1016/j.jsgi.2006.10.001


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