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

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Abstract

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 remodeling 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 expiants in pregnancies complicated by IUGR and 2) that oxygen levels affect such release.

Methods

Placental villous expiants 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 expiants 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 expiants from both normal (P <.001; P <.05) and IUGR (P <.05) pregnancies, MMP-2 release changed less in IUGR compared with normal expiant cultures. There were no significant effects of oxygen on MMP-9 release.

Conclusion

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

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Authors and Affiliations

  1. Department of Medical Microbiology and Immunology, 6-25 HMRC, Perinatal Research Centre, University of Alberta, Edmonton, Alberta, T6G 2S2, Canada

    S. J. Merchant MSc, I. P. Crocker PhD, P. N. Baker MD, PhD, D. Tansinda PhD, S. T. Davidge PhD & L. J. Guilbert PhD

  2. Maternal and Fetal Health Research Centre, St. Mary’s Hospital, Manchester, UK

    S. J. Merchant MSc, I. P. Crocker PhD, P. N. Baker MD, PhD, D. Tansinda PhD, S. T. Davidge PhD & L. J. Guilbert PhD

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  1. S. J. Merchant MSc
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  2. I. P. Crocker PhD
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  3. P. N. Baker MD, PhD
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  4. D. Tansinda PhD
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  5. S. T. Davidge PhD
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Additional information

S.J. Merchant is supported by the Province of Alberta Graduate Scholarship from the Faculty of Graduate Studies and Research, University of Alberta. S. T. Davidge is a Canada Research Chair and Senior Scholar of the Alberta Heritage Foundation for Medical Research. I. P. Crocker, P. N. Baker, and D. Tansinda are supported by Tommy’s — The Baby Charity. This research is supported by a grant to S. T. Davidge and L. J. Guilbert from the Canadian Institutes of Health Research (grant MOP42380).

The authors thank the research midwives and support staff at St. Mary’s Hospital, Manchester, United Kingdom for their assistance in the collection of samples

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Merchant, S.J., Crocker, I.P., Baker, P.N. et al. Matrix Metalloproteinase Release From Placental Explants of Pregnancies Complicated by Intrauterine Growth Restriction. Reprod. Sci. 11, 97–103 (2004). https://doi.org/10.1016/j.jsgi.2003.08.005

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