Secretion of matrix metalloproteinases 2 and 9 and tissue inhibitor of metalloproteinases into follicular fluid during follicle development in equine ovaries.
Abstract: Extensive tissue remodelling is required in equine ovaries for follicle growth and development and also migration of the follicle to the ovulatory fossa, where ovulation occurs. The mechanisms for these processes are largely unexplored. Matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs) are important for control of breakdown of extracellular matrix during tissue remodelling. The aims of this study were to determine the pattern and sites of secretion of the gelatinases MMP-2 and -9 and TIMPs into follicular fluid during follicle development in mare ovaries. The predominant gelatinase detected in follicular fluid was MMP-2, which was present in similar amounts throughout follicular development, as demonstrated by zymography. MMP-9 was also present in follicular fluid and secretion increased significantly (P < 0.05) with development of follicles from < 10 mm to 11-20 mm in diameter. Follicular fluid also contained TIMP-1, TIMP-2, unglycosylated and glycosylated TIMP-3, and TIMP-4, as shown by reverse zymography. The abundance of TIMPs remained largely unchanged during follicle development. MMP-2 and -9 were localized by immunohistochemistry to stromal cells and granulosa and theca cells. TIMP-1, -2, -3 and -4 were present in granulosa and theca cells of the follicle and in stromal cells and also associated with extracellular matrix of the ovarian stromal tissue. The MMPs and TIMPs are likely to be involved in the regulation of the breakdown of extracellular matrix during tissue remodelling for follicle development and migration to the ovulation fossa in mares.
Publication Date: 2001-03-30 PubMed ID: 11277874
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- Journal Article
Summary
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The study discerns the pattern and locations of certain enzymes (MMPs) and their inhibitors (TIMPs) in the fluid of ovarian follicles in horses, noting their relevance to ovarian tissue remodeling necessary for follicle growth and ovulation. MMP and TIMP levels varied during follicle development, suggesting these enzymes play a significant role in regulating tissue breakdown during this process.
Research Objectives and Approach
- The researchers sought to understand the role played by Matrix Metalloproteinases (MMPs) and Tissue Inhibitors of Metalloproteinases (TIMPs) in the growth and development of ovarian follicles in horses.
- MMPs and TIMPs are known to regulate the breakdown of the extracellular matrix, a process essential for tissue remodeling. This remodeling is needed for the growth of ovarian follicles and their migration toward the ovulatory fossa (the site of ovulation).
Research Findings
- The predominant enzyme found in the follicular fluid was MMP-2, whose presence didn’t vary significantly during follicle development.
- MMP-9 was also detected, with its secretion in the fluid increasing markedly as follicle size ranged from less than 10mm to between 11-20mm in diameter.
- The presence of TIMPs (TIMP-1, TIMP-2, TIMP-3, TIMP-4) was also confirmed in the follicular fluid. But unlike MMPs, the presence of these inhibitors didn’t alter significantly throughout follicle development.
Localization and Role of MMPs and TIMPs
- MMP-2 and -9 were found localized to stromal cells (connective tissue cells) and follicular cells (granulosa and theca cells).
- Similarly, all four TIMPs were present in granulosa and theca cells of the follicle, stromal cells and also in association with the extracellular matrix of the ovarian stromal tissue.
- These findings suggest a complex interplay between MMPs and TIMPs in the breaking down and building up of tissue during the growth and maturation of ovarian follicles, preparing them for ovulation.
Implications of the Study
- The study provides novel insights into the role of MMPs and TIMPs in ovarian follicle development, particularly concerning the regulatory mechanisms of tissue remodeling.
- Understanding the activities of these enzymes and inhibitors could offer a deeper understanding of follicular development and ovulation, potentially leading to breakthroughs in fertility research and treatment.
Cite This Article
APA
Riley SC, Gibson AH, Leask R, Mauchline DJ, Pedersen HG, Watson ED.
(2001).
Secretion of matrix metalloproteinases 2 and 9 and tissue inhibitor of metalloproteinases into follicular fluid during follicle development in equine ovaries.
Reproduction, 121(4), 553-560.
Publication
Researcher Affiliations
- Obstetrics and Gynaecology Section, Department of Reproductive and Developmental Sciences, University of Edinburgh, 37 Chalmers Street, Edinburgh EH3 9ET, UK. Simon.C.Riley@ed.ac.uk
MeSH Terms
- Animals
- Female
- Follicular Fluid / chemistry
- Follicular Fluid / enzymology
- Glycosylation
- Horses / physiology
- Immunohistochemistry
- Matrix Metalloproteinase 2 / analysis
- Matrix Metalloproteinase 2 / metabolism
- Matrix Metalloproteinase 9 / analysis
- Matrix Metalloproteinase 9 / metabolism
- Ovarian Follicle / chemistry
- Ovarian Follicle / physiology
- Ovary / chemistry
- Tissue Inhibitor of Metalloproteinase-1 / analysis
- Tissue Inhibitor of Metalloproteinase-1 / metabolism
- Tissue Inhibitor of Metalloproteinase-2 / analysis
- Tissue Inhibitor of Metalloproteinase-2 / metabolism
- Tissue Inhibitor of Metalloproteinase-3 / analysis
- Tissue Inhibitor of Metalloproteinase-3 / metabolism
- Tissue Inhibitor of Metalloproteinases / analysis
- Tissue Inhibitor of Metalloproteinases / metabolism
Citations
This article has been cited 10 times.- Hyde KA, Aguiar FLN, Alves BG, Alves KA, Gastal GDA, Gastal MO, Gastal EL. Preantral follicle population and distribution in the horse ovary. Reprod Fertil 2022 Apr 1;3(2):90-102.
- Zhu Y. Metalloproteases in gonad formation and ovulation. Gen Comp Endocrinol 2021 Dec 1;314:113924.
- Alves BG, Alves KA, Gastal GDA, Gastal MO, Figueiredo JR, Gastal EL. Spatial distribution of preantral follicles in the equine ovary. PLoS One 2018;13(6):e0198108.
- Yang WJ, Liu FC, Hsieh JS, Chen CH, Hsiao SY, Lin CS. Matrix metalloproteinase 2 level in human follicular fluid is a reliable marker of human oocyte maturation in in vitro fertilization and intracytoplasmic sperm injection cycles. Reprod Biol Endocrinol 2015 Sep 4;13:102.
- Kim SH, Kang CW, Min KS, Yoon JT. Matrix metalloproteinases are important for follicular development in normal and miniature pigs. Biotechnol Lett 2014 Jun;36(6):1187-96.
- Rosewell KL, Li F, Puttabyatappa M, Akin JW, Brännström M, Curry TE Jr. Ovarian expression, localization, and function of tissue inhibitor of metalloproteinase 3 (TIMP3) during the periovulatory period of the human menstrual cycle. Biol Reprod 2013 Nov;89(5):121.
- Galvão AM, Ferreira-Dias G, Skarzynski DJ. Cytokines and angiogenesis in the corpus luteum. Mediators Inflamm 2013;2013:420186.
- Horka P, Malickova K, Jarosova R, Janatkova I, Zima T, Kalousova M. Matrix metalloproteinases in serum and the follicular fluid of women treated by in vitro fertilization. J Assist Reprod Genet 2012 Nov;29(11):1207-12.
- Jankowska-Ziemak H, Kulus M, Partynska A, Kulus J, Data KP, Domagala D, Niebora J, Gorska A, Podralska M, Podhorska-Okolow M, Chmielewski P, Antosik P, Bukowska D, Kaminski A, Piotrowska-Kempisty H, Zabel M, Mozdziak P, Dziegiel P, Kempisty B. The Role of Growth Factors and Signaling Pathways in Ovarian Angiogenesis. Cells 2025 Oct 7;14(19).
- Albeitawi S, Bani-Mousa SU, Jarrar B, Aloqaily I, Al-Shlool N, Alsheyab G, Kassab A, Qawasmi B, Awaisheh A. Associations Between Follicular Fluid Biomarkers and IVF/ICSI Outcomes in Normo-Ovulatory Women-A Systematic Review. Biomolecules 2025 Mar 20;15(3).
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