Polymorphism of the MMP-2, MMP-9, TIMP-2 genes and the expression pattern of matrix metalloproteinases types 2 and 9 of the placenta of women with recurrent miscarriage
https://doi.org/10.29235/1814-6023-2025-22-1-65-72
Abstract
Expression indices of matrix metalloproteinases (MMPs) of types 2 and 9 and polymorphism of MMP-2, MMP-9 and their tissue inhibitor (TIMP-2) genes in placental tissue of women with early reproductive losses were determined. MMP-2 expression in placental tissue preparations was found to be significantly higher among women with recurrent miscarriage in the first trimester pregnancy than in women with normal pregnancy. Associations of the mutant T allele of the 735 C/T polymorphism of the MMP-2 gene and the mutant C allele of the 418 G/C polymorphism of the TIMP-2 gene with a high level of matrix MMP-2 expression were found. The level of MMP-9 expression in the placenta of women with recurrent miscarriage and with physiological pregnancy was not statistically significantly different.
Supporting agencies: The work was financially suppor- ted by the intra-university research grant for postgraduate students, doctoral students and academic staff of Grodno State Medical University “Analysis of associations of allelic variants of genes of the matrix metalloproteinase system type nine with early embryonic loss in women with habitual miscarriage of pregnancy” (2022).
About the Authors
T. N. Grinevich
Grodno State Medical University
Belarus
Belarus
Tatyana N. Grinevich – Ph. D. (Med.), Associate Professor
80, Gorky Str., 230015, Grodno
S. A. Lyalikov
Grodno State Medical University
Belarus
Belarus
Sergey A. Lyalikov – D. Sc. (Med.), Professor, Head of the Department
80, Gorky Str., 230015, Grodno
A. V. Shulga
Grodno State Medical University
Belarus
Belarus
Andrey V. Shulga – Ph. D. (Med.), Associate Professor
80, Gorky Str., 230015, Grodno
M. O. Kot
Grodno State Medical University
Belarus
Belarus
Maksim O. Kot – Student
80, Gorky Str., 230015, Grodno
References
1. Goldman S., Weiss A., Eyali V., Shalev E. Differential activity of the gelatinases (matrix metalloproteinases 2 and 9) in the fetal membranes and decidua, associated with labour. Molecular Human Reproduction, 2003, vol. 9, no. 6, pp. 367–373. https://doi.org/10.1093/molehr/gag040
2. Staun-Ram E., Goldman S., Gabarin D., Shalev E. Expression and importance of matrix metalloproteinase 2 and 9 (MMP-2 and -9) in human trophoblast invasion. Reproductive Biology and Endocrinology, 2004, vol. 2, art. 59. https://doi.org/10.1186/1477-7827-2-59
3. Moore C. S., Crocker S. J. An alternate perspective on the roles of TIMPs and MMPs in pathology. American Journal of Pathology, 2012, vol. 180, no. 1, pp. 12–16. https://doi.org/10.1016/j.ajpath.2011.09.008
4. Alexander C. M., Hansell E. J., Behrendtsen O., Flannery M. L., Kishnani N. S., Hawkes S. P., Werb Z. Expression and function of matrix metalloproteinases and their inhibitors at the maternal-embryonic boundary during mouse embryo implantation. Development, 1996, vol. 122, pp. 1723–1736. https://doi.org/10.1242/dev.122.6.1723
5. Turpeenniemi-Hujanen T., Feinberg R. F., Kauppila A., Puistola U. Extracellular matrix interactions in early human embryos: implications for normal implantation events. Fertility and Sterility, 1995, vol. 64, no. 1, pp. 132–138.
6. Canete-Soler R., Gui Y. H., Linask K. K., Muschel R. J. Developmental expression of MMP-9 (gelatinase B) mRNA in mouse embryos. Developmental Dynamics, 1995, vol. 204, no. 1, pp. 30–40. https://doi.org/10.1002/aja.1002040105
7. Tikhaeva K. Yu., Rogova L. N., Tkachenko L. V. The role of metalloproteinases in the exchange of endometrial extracellular matrix proteins in normal and pathological conditions. Problemy reproduktsii [Reproductive problems], 2020, vol. 26, no. 4, pp. 22–29 (in Russian).
8. Yu W. H., Yu S., Meng Q., Brew K., Woessner J. F. TIMP-3 binds to sulfated glycosaminoglycans of the extracellular matrix. Journal of Biological Chemistry, 2000, vol. 275, no. 40, pp. 31226–31232. https://doi.org/10.1074/jbc.M000907200
9. Polette M., Nawrocki B., Pintiaux A., Massenat Ch., Maquoi E., Volders L., Schaaps J., Birembaut Ph. L., Foidart J. Expression of gelatinases A and B and their tissue inhibitors by cells of early and term human placenta and gestational endometrium. Laboratory Investigation, 1994, vol. 71, no. 6, pp. 838–846.
10. Cross J. C., Werb Z., Fisher S. J. Implantation and the placenta: Key pieces of the development puzzle. Science, 1994, vol. 266, no. 5190, pp. 1508–1518. https://doi.org/10.1126/science.7985020
11. Hampton A. L., Butt A. R., Riley S. C., Salamonsen L. A. Tissue inhibitors of metalloproteinases in endometrium of ovariectomized steroid-treated ewes and during the estrous cycle and early pregnancy. Biology of Reproduction, 1995, vol. 53, no. 2, pp. 302–311. https://doi.org/10.1095/biolreprod53.2.302
12. Aresu L., Benali S., Giannuzzi D., Mantovani R., Castagnaro M., Falomo M. The role of inflammation and matrix metalloproteinases in equine endometriosis. Journal of Veterinary Science, 2012, vol. 13, no. 2, pp. 171–177. https://doi.org/10.4142/jvs.2012.13.2.171
Review
For citations:
Grinevich T.N., Lyalikov S.A., Shulga A.V., Kot M.O. Polymorphism of the MMP-2, MMP-9, TIMP-2 genes and the expression pattern of matrix metalloproteinases types 2 and 9 of the placenta of women with recurrent miscarriage. Proceedings of the National Academy of Sciences of Belarus, Medical series. 2025;22(1):65-72. (In Russ.) https://doi.org/10.29235/1814-6023-2025-22-1-65-72
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