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Journal of the Society for Gynecologic Investigation, Vol. 11, No. 2, 97-103 (2004)
DOI: 10.1016/j.jsgi.2003.08.005

Matrix Metalloproteinase Release From Placental Explants of Pregnancies Complicated by Intrauterine Growth Restriction

S. J. Merchant, MSc

I. P. Crocker, PhD

P. N. Baker, MD, PhD

D. Tansinda, PhD

S. T. Davidge, PhD

Perinatal Research Centre, University of Alberta, Edmonton, Alberta, Canada; Maternal and Fetal Health Research Centre, St. Mary's Hospital, Manchester, United Kingdom

L. J. Guilberg, PhD

Perinatal Research Centre, University of Alberta, Edmonton, Alberta, Canada; Maternal and Fetal Health Research Centre, St. Mary's Hospital, Manchester, United Kingdom; Department of Medical Microbiology and Immunology, 6-25 HMRC, University of Albert, Edmonton, Alberta, T6G 2S2 Canada; larry.guilbert{at}ualberta.ca

Objective: There is evidence of impaired placental development in intrauterine growth restriction (IUGR). Matrix metalloproteinases (MMPs) are extracellular matrix-degrading enzymes that are released by placental cells during tissue remodelling processes. We hypothesized 1) that release of MMP-2 and -9 is decreased and/or release of tissue inhibitors of metalloproteinases (TIMPs) is increased from placental explants in pregnancies complicated by IUGR and 2) that oxygen levels affect such release.

Methods: Placental villous explants from normal (n = 7) and IUGR (n = 7) pregnancies were cultured at high (20%) and low (3%) oxygen levels for 24 hours. Supernatants were analyzed for MMP-2 and MMP-9 by zymography and for TIMP-1 and -2 by western blot analysis.

Results: At 20% oxygen there was significantly reduced MMP-2 (P < .05) and TIMP-1 (P < .01) release and a trend for decreased MMP-9 release (P = .07) in explants from IUGR pregnancies compared with normal pregnancies; however, there were no differences at 3% oxygen. TIMP-2 was below detectable levels in all samples. Although MMP-2 and TIMP-1 release was significantly reduced at 3% compared with 20% oxygen in explants from both normal (P < .001; P < .05) and IUGR (P < .05) pregnancies, MMP-2 release changed less in IUGR compared with normal explant cultures. There were no significant effects of oxygen on MMP-9 release.

Conclusion: Placental explaints from IUGR pregnancies demonstrated reduced MMP-2, MMP-9, and TIMP-1 release compared with explants from normal pregnancies at high (20%) but not low (3%) oxygen.

Key Words: Matrix metalloproteinases • tissue inhibitors of metalloproteinases • intrauterine growth restriction • oxygen


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