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Circulating levels of matrix proteases and their inhibitors in pregnant women with and without a history of recurrent pregnancy loss

Anumba, D.O.C., El Gelany, S., Elliott, S.L. and Li, T.C. (2010) Circulating levels of matrix proteases and their inhibitors in pregnant women with and without a history of recurrent pregnancy loss. Reproductive Biology and Endocrinology, 8. Art no.62. ISSN 1477-7827

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Background: We have recently shown that serum relaxin-2 levels are attenuated in women with a history of recurrent pregnancy loss (RPL). We sought to determine whether a history of RPL is also associated with changes in serum matrix metalloproteases (MMPs) and tissue inhibitors of matrix metalloproteases (TIMP) -1 and -2.

Methods: We obtained serum from 20 pregnant women with a history of RPL and 20 age-matched pregnant women with no history of RPL (NRPL) at 6-8, 10-12, 20, and 34 weeks gestation, and from cord blood. We quantified total serum concentrations of MMP-1, MMP-3, MMP-9 and TIMP-1 and TIMP-2 by ELISA. We determined whether these serum marker levels were associated with a history of RPL and delivery before 37 weeks gestation.

Results: There was no difference in the rates of miscarriage, preterm birth or prelabour rupture of fetal membranes between RPL and NRPL. However babies born to RPL were lighter than those born to NRPL. Serum MMP-1, 9, and TIMP-1 did not differ between RPL and NRPL but MMP-3 was higher in RPL vs. NRPL at 6-8 weeks (P < 0.05). Serum TIMP-2 levels were higher in RPL women at all gestations (P < 0.01). The ratio of RLX-2 (reported previously) to TIMP-2 at 10-12 weeks gestation was more strongly associated with a history of RPL than either peptide separately - area under the ROC curves for RLX-2 0.79 (95% CI 0.57 to 0.92), TIMP-2 0.83 (95% CI 0.63 to 0.95), and for RLX-2: TIMP-2 ratio 0.92 (95% CI 0.74 to 0.99).

Conclusions: Women with a history of RPL demonstrate increased serum TIMP-2 and reduced RLX-2 during a subsequent viable pregnancy. Determination of both markers in early pregnancy enhances the discrimination of women with a history of RPL. These observations suggest roles for these two peptides in early implantation and placental development. Whether these may prove to be reliable early predictive markers for subsequent pregnancy loss in the index pregnancy is unknown and will require further studies.

Item Type: Article
Copyright, Publisher and Additional Information: © 2010 Anumba et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Tissue Inhibitors; Metalloproteinase (MMP)-2; Insulin-Resistance; First-Trimester; Messenger-RNA; Growth-Factor; Miscarriage; Cells; Preeclampsia; TIMP-2
Institution: The University of Sheffield
Academic Units: The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine (Sheffield) > Clinical Sciences Division South (Sheffield) > Reproductive and Developmental Medicine (Sheffield)
Depositing User: Miss Anthea Tucker
Date Deposited: 12 Aug 2010 10:12
Last Modified: 14 Jun 2014 16:05
Published Version: http://dx.doi.org/10.1186/1477-7827-8-62
Status: Published
Publisher: BioMed Central
Refereed: Yes
Identification Number: 10.1186/1477-7827-8-62
URI: http://eprints.whiterose.ac.uk/id/eprint/11109

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