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Circulating matrix metalloproteinase MMP-9 and MMP-2/TIMP-2 complex are associated with spontaneous early pregnancy failure

Ritva Nissi1*, Anne Talvensaari-Mattila1, Vesa Kotila2, Maarit Niinimäki1, Ilkka Järvelä1 and Taina Turpeenniemi-Hujanen3

Author Affiliations

1 Department of Obstetrics and Gynecology, Oulu University Hospital, Kajaanintie 52A, Oulu, 90220, Finland

2 Department of Electrical Engineering, Division of Mathematics, University of Oulu, Finland

3 Department of Oncology and Radiotherapy, Oulu University Hospital, Kajaanintie 52A, Oulu, 90220, Finland

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Reproductive Biology and Endocrinology 2013, 11:2  doi:10.1186/1477-7827-11-2

Published: 15 January 2013



Trophoblast cell (CTB) invasion into the maternal endometrium plays a crucial role during human embryo implantation and placentation. This invasion is facilitated by the activity of matrix metalloproteinases, which are regulated by tissue inhibitors of MMPs (TIMPs).


This study compares the serum levels of MMP-9, MMP-2/TIMP-2 complex, TIMP-1 and TIMP-2 in 129 patients with ongoing pregnancy (n = 40) or spontaneous early pregnancy failure (n = 89).


MMP-9 was markedly (p < 0.0001) elevated in missed abortions, as was MMP-2/TIMP-2 complex (p < 0.0005). However, the serum levels of TIMP-1 and TIMP-2 were markedly elevated (p < 0.0001) in ongoing pregnancies.


Human placentation is mediated by fetal trophoblastic cells that invade the maternal uterine endometrium. Trophoblast invasion requires a precisely regulated secretion of specific proteolytic enzymes able to degrade the endometrial basement membrane and extracellular matrix. The elevated levels of MMP-9 and MMP-2/TIMP-2 complex may play a role in spontaneous termination of pregnancy.

MMP-2; MMP-9; TIMP-1; TIMP-2; Pregnancy; Pregnancy loss; Serum marker; Placentation