EN
Immunohistochemical study of matrix metalloproteinases 2 and 9 in the placenta of spontaneous miscarriage
Abstract
Miscarriage is the termination of pregnancy by spontaneous expulsion of embryo/fetus before 25 weeks of gestation or when the fetus weighs less than 500 grams. It is the most common pregnancy problem, impacting around 10% to 15% of all pregnancies. Matrix metalloproteinase 2 and 9 (MMP-2 and MMP-9) play a crucial role in embryo implantation and placentation; spontaneous abortion has been observed when there is abnormal expression of MMP-2 and MMP-9 levels. This research aims to evaluate the expression of MMP-2 and MMP-9 in the placenta of women with spontaneous miscarriage. The placental specimens were collected from 30 women who had delivered normally as a control group, 30 women who had miscarried in the first trimester, and 30 women who had miscarried in the second trimester. The specimens included the decidua basalis and trophoblast. The expression patterns of MMP-2 and MMP-9 were examined using the immunohistochemical study. Antibodies were used against MMP2 and MMP9. The results revealed a strong expression of MMP-2 and MMP-9 in the placenta of normally delivered women; 18 and 20 cases of first and second-trimester miscarriage showed weak expression of MMP-2, while 12 and 10 cases of both trimesters revealed moderate expression. MMP-9 showed weak expression in decidua and trophoblastic tissue of 26 and 24 cases of the first and second trimester, 4 and 6 specimens reported moderate expression in the first and second-trimester miscarriage, and significant differences were detected between the study groups (p-value <0.01). We conclude that MMP-2 and MMP-9 immunopositivity could indicate uncontrolled invasion of trophoblasts, leading to their destructive invasion and contributing to spontaneous miscarriage pathogenesis.
Keywords
References
- [1] Erra S, Merlo C. Early Miscarriage: Morphological Data Useful to Clinical and Nosographic Classification. Int J Appl Pharm Sci Res. 2019;4(2):13-16. https://doi.org/10.21477/ijapsr.4.2.1.
- [2] Linnakaari R, Helle N, Mentula M, Bloigu A, Gissler M, Heikinheimo O, Niinimäki M. Trends in the incidence, rate and treatment of miscarriage-nationwide register-study in Finland, 1998-2016. Hum Reprod. 2019;34(11):2120- 2128. https://doi.org/10.1093/humrep/dez211.
- [3] Woolner AM, Nagdeve P, Raja EA, Bhattacharya S, Bhattacharya S. Family history and risk of miscarriage: A systematic review and meta‐analysis of observational studies. Acta Obstet Gynecol Scand. 2020;99(12):1584-1594. https://doi.org/10.1111/aogs.13940.
- [4] 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. Reprod Biol Endocrinol. 2004;2:59. https://doi.org/10.1186%2F1477- 7827-2-59.
- [5] Castruita-De la Rosa C, Garza-Veloz I, Delgado-Enciso I, Olivas-Chavez JC, Cardenas-Vargas E, Rodriguez-Sanchez IP, Francisco Citalan-Madrid A, Ortega-Cisneros V, Isaias Badillo-Almaraz J, Maria Trejo-Ortiz P, Araujo-Espino R, Araujo-Conejo A, de Jesus Jaime-Guzman J, Martinez-Fierro ML. Spontaneous abortion is preceded by an altered serum concentration of matrix metalloproteinases. J Matern Fetal Neonatal Med. 2020;33(24):4108-4116. https://doi.org/10.1080/14767058.2019.1597046.
- [6] Jing M, Chen X, Qiu H, He W, Zhou Y, Li D, Wang D, Jiao Y, Liu A. Insights into the immunomodulatory regulation of matrix metalloproteinase at the maternal-fetal interface during early pregnancy and pregnancy-related diseases. Front Immunol. 2023;13:1067661. https://doi.org/10.3389/fimmu.2022.1067661.
- [7] Zhang SM, Tian FJ, Zeng WH, Ma XL, Ren JB, Lin Y. XCL 1‐XCR 1 pathway promotes trophoblast invasion at maternal‐fetal interface by inducing MMP‐2/MMP‐9 activity. Am J Reprod Immunol. 2018;80(3):e12990. https://doi.org/10.1111/aji.12990.
- [8] Singh M, Kindelberger D, Nagymanyoki Z, Ng SW, Quick CM, Elias KM, Yamamoto H, Fichorova R, Fulop V, Berkowitz RS. Matrix metalloproteinases and their inhibitors and inducer in gestational trophoblastic diseases and normal placenta. Gynecol Oncol. 2011;122(1):178-182. https://doi.org/10.1016/j.ygyno.2011.03.025.
Details
Primary Language
English
Subjects
Pharmacology and Pharmaceutical Sciences (Other)
Journal Section
Research Article
Publication Date
September 1, 2025
Submission Date
September 23, 2024
Acceptance Date
October 10, 2024
Published in Issue
Year 2025 Volume: 29 Number: 5
APA
Hassan, R., & Haba, M. K. (2025). Immunohistochemical study of matrix metalloproteinases 2 and 9 in the placenta of spontaneous miscarriage. Journal of Research in Pharmacy, 29(5), 2064-2076. https://doi.org/10.12991/jrespharm.1766301
AMA
1.Hassan R, Haba MK. Immunohistochemical study of matrix metalloproteinases 2 and 9 in the placenta of spontaneous miscarriage. J. Res. Pharm. 2025;29(5):2064-2076. doi:10.12991/jrespharm.1766301
Chicago
Hassan, Russul, and Mukhtar K. Haba. 2025. “Immunohistochemical Study of Matrix Metalloproteinases 2 and 9 in the Placenta of Spontaneous Miscarriage”. Journal of Research in Pharmacy 29 (5): 2064-76. https://doi.org/10.12991/jrespharm.1766301.
EndNote
Hassan R, Haba MK (September 1, 2025) Immunohistochemical study of matrix metalloproteinases 2 and 9 in the placenta of spontaneous miscarriage. Journal of Research in Pharmacy 29 5 2064–2076.
IEEE
[1]R. Hassan and M. K. Haba, “Immunohistochemical study of matrix metalloproteinases 2 and 9 in the placenta of spontaneous miscarriage”, J. Res. Pharm., vol. 29, no. 5, pp. 2064–2076, Sept. 2025, doi: 10.12991/jrespharm.1766301.
ISNAD
Hassan, Russul - Haba, Mukhtar K. “Immunohistochemical Study of Matrix Metalloproteinases 2 and 9 in the Placenta of Spontaneous Miscarriage”. Journal of Research in Pharmacy 29/5 (September 1, 2025): 2064-2076. https://doi.org/10.12991/jrespharm.1766301.
JAMA
1.Hassan R, Haba MK. Immunohistochemical study of matrix metalloproteinases 2 and 9 in the placenta of spontaneous miscarriage. J. Res. Pharm. 2025;29:2064–2076.
MLA
Hassan, Russul, and Mukhtar K. Haba. “Immunohistochemical Study of Matrix Metalloproteinases 2 and 9 in the Placenta of Spontaneous Miscarriage”. Journal of Research in Pharmacy, vol. 29, no. 5, Sept. 2025, pp. 2064-76, doi:10.12991/jrespharm.1766301.
Vancouver
1.Russul Hassan, Mukhtar K. Haba. Immunohistochemical study of matrix metalloproteinases 2 and 9 in the placenta of spontaneous miscarriage. J. Res. Pharm. 2025 Sep. 1;29(5):2064-76. doi:10.12991/jrespharm.1766301