The role of inflammation and matrix metalloproteinases in equine endometriosis.
Abstract: Equine endometriosis is a multifactorial disease considered to be a major cause of equine infertility. The purpose of this study was to evaluate the reliability of histomorphological grading for biopsy-like samples compared to entire uterine wall samples, to examine the association between the degree of endometriosis with animal age, and to investigate the role of inflammation in endometriosis and the expression of different matrix metalloproteinases in equine endometrium. Histomorphological lesions in 35 uterine samples were examined while comparing biopsy-like samples and entire-wall samples. Seventeen uterine samples were stained with antibodies against MMP-2, MMP-9, MMP-14, and TIMP-2. The morphologic evaluation results of the biopsy-like tissue and entire-wall samples were significantly correlated. Endometriosis in older mares (>12 years of age) was more severe than in young mares (2 ~ 4 years of age), confirming the positive correlation between animal age and disease severity, while inflammation was poorly related to the degree of endometriosis. MMP-2 and MMP-14 were detected in stromal cells, while MMP-9 and TIMP-2 were both found in stromal and glandular epithelial cells. There were no significant differences in MMPs expression between the two groups (young vs. old mares). Additional studies on the activity of MMPs could further define the role of these enzymes in equine endometriosis.
Publication Date: 2012-06-19 PubMed ID: 22705739PubMed Central: PMC3386342DOI: 10.4142/jvs.2012.13.2.171Google Scholar: Lookup
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- Journal Article
Summary
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This study investigates the severity of endometriosis in horses, its correlation with age, and association with inflammation and certain enzymes. The study revealed that older mares suffer more severe endometriosis than their younger counterparts, and that the presence and severity of the condition may be linked to the activity of specific enzymes, rather than inflammation.
Understanding the Study and its Objectives
- The study was designed to evaluate the reliability of grading equine endometriosis using biopsy samples compared to using entire uterine wall samples. This was aimed at determining if smaller samples could reliably represent the extent of the condition.
- The researchers also wanted to establish the correlation between equine age and the severity of endometriosis. This aspect of the study was necessary to understand whether the disease becomes more severe as horses grow older.
- The final objective was to investigate the role of inflammation in endometriosis, as well as to examine the expression of different matrix metalloproteinases in the uterine tissue of horses. Matrix metalloproteinases (MMPs) are enzymes implicated in tissue remodeling and may play a role in the development of endometriosis.
Methods and Findings
- 35 uterine samples were taken and examined for lesions, and compared across biopsy-like samples and whole uterine wall samples.
- The severity of endometriosis was generally more pronounced in older mares than in younger ones, suggesting a direct correlation between a horse’s age and the severity of the disease.
- Inflammation didn’t show a clear relationship with the severity of endometriosis in the sample population, suggesting that inflammation may not be a significant factor in the development or progression of equine endometriosis.
- Various MMPs were found in the stromal cells and glandular epithelial cells in the uterine tissue. These enzymes may have a role in the maintenance or progression of the disease.
Implications and Future Direction
- The findings of this study suggest that more comprehensive studies on the activity of these MMPs and their influence on equine endometriosis are warranted. This can potentially open a new research direction towards understanding this disease better and developing effective treatments.
- This study also provides useful insights that can aid in the diagnosis and grading of equine endometriosis using biopsy-like tissue samples.
Cite This Article
APA
Aresu L, Benali S, Giannuzzi D, Mantovani R, Castagnaro M, Falomo ME.
(2012).
The role of inflammation and matrix metalloproteinases in equine endometriosis.
J Vet Sci, 13(2), 171-177.
https://doi.org/10.4142/jvs.2012.13.2.171 Publication
Researcher Affiliations
- Dipartimento di Sanità Pubblica, Patologia Comparata e Igiene Veterinaria, Facoltà di Medicina Veterinaria, Viale dell'Università, 16-35020-Legnaro (Padova) 049-8272963, Italy. luca.aresu@unipd.it
MeSH Terms
- Animals
- Endometriosis / metabolism
- Endometriosis / pathology
- Endometriosis / veterinary
- Female
- Gene Expression Regulation, Enzymologic / physiology
- Horse Diseases / metabolism
- Horse Diseases / pathology
- Horses
- Immunohistochemistry / veterinary
- Inflammation / pathology
- Inflammation / veterinary
- Matrix Metalloproteinases / genetics
- Matrix Metalloproteinases / metabolism
- Uterus / metabolism
- Uterus / pathology
References
This article includes 29 references
- Aresu L, Benali S, Garbisa S, Gallo E, Castagnaro M. Matrix metalloproteinases and their role in the renal epithelial mesenchymal transition.. Histol Histopathol 2011 Mar;26(3):307-13.
- Aresu L, Giantin M, Morello E, Vascellari M, Castagnaro M, Lopparelli R, Zancanella V, Granato A, Garbisa S, Aricò A, Bradaschia A, Mutinelli F, Dacasto M. Matrix metalloproteinases and their inhibitors in canine mammary tumors.. BMC Vet Res 2011 Jul 4;7:33.
- Cadario ME, Losinno L, Giguere S, Aguilar J, MacPherson M, Fitzpatrick C, Uhl E. Uterine expression of fibrogenic cytokines in the mare.. Theriogenology 2002;58:449–452.
- Clutterbuck AL, Harris P, Allaway D, Mobasheri A. Matrix metalloproteinases in inflammatory pathologies of the horse.. Vet J 2010 Jan;183(1):27-38.
- de Laat MA, Kyaw-Tanner MT, Nourian AR, McGowan CM, Sillence MN, Pollitt CC. The developmental and acute phases of insulin-induced laminitis involve minimal metalloproteinase activity.. Vet Immunol Immunopathol 2011 Apr 15;140(3-4):275-81.
- Doig PA, McKnight JD, Miller RB. The use of endometrial biopsy in the infertile mare.. Can Vet J 1981 Mar;22(3):72-6.
- Dybdal NO, Daels PF, Couto MA, Hughes JP, Kennedy PC. Investigation of the reliability of a single endometrial biopsy sample, with a note on the correlation between uterine cysts and biopsy grade.. J Reprod Fertil Suppl 1991;44:697.
- Fiala SM, Esmeraldino A, Jobim MIM, Garbade P, Wolf CA, Richter G, Gregory RM, Mattos RC. Endometrial fibrotic changes. Is one biopsy enough to diagnose degenerative changes?. Anim Reprod Sci 2010;121(Suppl):S89–S90.
- Flores JM, Rodríguez A, Sánchez J, Gómez-Cuétara C, Ramiro F. Endometrosis in mares: incidence of histopathological alterations.. Reprod Domest Anim 1995;30:61–65.
- Giantin M, Aresu L, Benali S, Aricò A, Morello EM, Martano M, Vascellari M, Castagnaro M, Lopparelli RM, Zancanella V, Granato A, Mutinelli F, Dacasto M. Expression of matrix metalloproteinases, tissue inhibitors of metalloproteinases and vascular endothelial growth factor in canine mast cell tumours.. J Comp Pathol 2012 Nov;147(4):419-29.
- Hoffmann C, Ellenberger C, Mattos RC, Aupperle H, Dhein S, Stief B, Schoon HA. The equine endometrosis: new insights into the pathogenesis.. Anim Reprod Sci 2009 Apr;111(2-4):261-78.
- Kenney RM. Cyclic and pathologic changes of the mare endometrium as detected by biopsy, with a note on early embryonic death.. J Am Vet Med Assoc 1978 Feb 1;172(3):241-62.
- Kenney RM, Doig PA. Equine endometrial biopsy.. In: Morrow DA, editor. Current Therapy in Theriogenology. 2nd ed. Philadelphia: Saunders; 1986. pp. 723–729.
- Kenney RM, Ganjam VK. Selected pathological changes of the mare uterus and ovary.. J Reprod Fertil Suppl 1975 Oct;(23):335-9.
- Loftus JP, Belknap JK, Black SJ. Matrix metalloproteinase-9 in laminae of black walnut extract treated horses correlates with neutrophil abundance.. Vet Immunol Immunopathol 2006 Oct 15;113(3-4):267-76.
- Loftus JP, Johnson PJ, Belknap JK, Pettigrew A, Black SJ. Leukocyte-derived and endogenous matrix metalloproteinases in the lamellae of horses with naturally acquired and experimentally induced laminitis.. Vet Immunol Immunopathol 2009 Jun 15;129(3-4):221-30.
- McCawley LJ, Matrisian LM. Matrix metalloproteinases: they're not just for matrix anymore!. Curr Opin Cell Biol 2001 Oct;13(5):534-40.
- Mishra B, Kizaki K, Koshi K, Ushizawa K, Takahashi T, Hosoe M, Sato T, Ito A, Hashizume K. Expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and its related extracellular matrix degrading enzymes in the endometrium during estrous cycle and early gestation in cattle.. Reprod Biol Endocrinol 2010 Jun 11;8:60.
- Mott JD, Werb Z. Regulation of matrix biology by matrix metalloproteinases.. Curr Opin Cell Biol 2004 Oct;16(5):558-64.
- Nagase H, Visse R, Murphy G. Structure and function of matrix metalloproteinases and TIMPs.. Cardiovasc Res 2006 Feb 15;69(3):562-73.
- Osenkowski P, Toth M, Fridman R. Processing, shedding, and endocytosis of membrane type 1-matrix metalloproteinase (MT1-MMP).. J Cell Physiol 2004 Jul;200(1):2-10.
- Ricketts SW, Alonso S. The effect of age and parity on the development of equine chronic endometrial disease.. Equine Vet J 1991 May;23(3):189-92.
- Skinner JL, Riley SC, Gebbie AE, Glasier AF, Critchley HO. Regulation of matrix metalloproteinase-9 in endometrium during the menstrual cycle and following administration of intrauterine levonorgestrel.. Hum Reprod 1999 Mar;14(3):793-9.
- Troedsson MHT. Diseases of the uterus.. In: Robinson NE, editor. Current Therapy in Equine Medicine. 4th ed. Philadelphia: Saunders; 1997. pp. 517–523.
- Uekita T, Tanaka SS, Sato H, Seiki M, Tojo H, Tachi C. Expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) mRNA in trophoblast and endometrial epithelial cell populations of the synepitheliochorial placenta of goats (Capra hircus).. Arch Histol Cytol 2001 Oct;64(4):411-24.
- Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry.. Circ Res 2003 May 2;92(8):827-39.
- Walter I, Handler J, Miller I, Aurich C. Matrix metalloproteinase 2 (MMP-2) and tissue transglutaminase (TG 2) are expressed in periglandular fibrosis in horse mares with endometrosis.. Histol Histopathol 2005 Oct;20(4):1105-13.
- Walter I, Handler J, Reifinger M, Aurich C. Association of endometriosis in horses with differentiation of periglandular myofibroblasts and changes of extracellular matrix proteins.. Reproduction 2001 Apr;121(4):581-6.
- Zhang J, Salamonsen LA. Tissue inhibitor of metalloproteinases (TIMP)-1, -2 and -3 in human endometrium during the menstrual cycle.. Mol Hum Reprod 1997 Sep;3(9):735-41.
Citations
This article has been cited 18 times.- Alpoim-Moreira J, Fernandes C, Pimenta J, Bliebernicht M, Rebordão MR, Castelo-Branco P, Szóstek-Mioduchowska A, Skarzynski DJ, Ferreira-Dias G. Metallopeptidades 2 and 9 genes epigenetically modulate equine endometrial fibrosis. Front Vet Sci 2022;9:970003.
- Alpoim-Moreira J, Fernandes C, Rebordão MR, Costa AL, Bliebernicht M, Nunes T, Szóstek-Mioduchowska A, Skarzynski DJ, Ferreira-Dias G. Collagen Type III as a Possible Blood Biomarker of Fibrosis in Equine Endometrium. Animals (Basel) 2022 Jul 21;12(14).
- Katila T, Ferreira-Dias G. Evolution of the Concepts of Endometrosis, Post Breeding Endometritis, and Susceptibility of Mares. Animals (Basel) 2022 Mar 19;12(6).
- Cheng J, Li C, Ying Y, Lv J, Qu X, McGowan E, Lin Y, Zhu X. Metformin Alleviates Endometriosis and Potentiates Endometrial Receptivity via Decreasing VEGF and MMP9 and Increasing Leukemia Inhibitor Factor and HOXA10. Front Pharmacol 2022;13:750208.
- Jasiński T, Zdrojkowski Ł, Kautz E, Juszczuk-Kubiak E, Ferreira-Dias G, Domino M. The NF-κB-signalling pathway in mare's endometrium infiltrated with the inflammatory cells. Reprod Domest Anim 2022 Jun;57(6):598-610.
- Amaral A, Fernandes C, Rebordão MR, Szóstek-Mioduchowska A, Lukasik K, Pinto-Bravo P, Telo da Gama L, Jan Skarzynski D, Ferreira-Dias G. Myeloperoxidase Inhibition Decreases the Expression of Collagen and Metallopeptidase in Mare Endometria under In Vitro Conditions. Animals (Basel) 2021 Jan 16;11(1).
- Amaral A, Fernandes C, Morazzo S, Rebordão MR, Szóstek-Mioduchowska A, Lukasik K, Gawronska-Kozak B, Telo da Gama L, Skarzynski DJ, Ferreira-Dias G. The Inhibition of Cathepsin G on Endometrial Explants With Endometrosis in the Mare. Front Vet Sci 2020;7:582211.
- Szóstek-Mioduchowska A, Słowińska M, Pacewicz J, Skarzynski DJ, Okuda K. Matrix metallopeptidase expression and modulation by transforming growth factor-β1 in equine endometrosis. Sci Rep 2020 Jan 24;10(1):1119.
- Crociati M, Capomaccio S, Mandara MT, Stradaioli G, Sylla L, Monaci M, Cappelli K. Different expression of Defensin-B gene in the endometrium of mares of different age during the breeding season. BMC Vet Res 2019 Dec 21;15(1):465.
- Siemieniuch MJ, Szóstek AZ, Gajos K, Kozdrowski R, Nowak M, Okuda K. Type of Inflammation Differentially Affects Expression of Interleukin 1β and 6, Tumor Necrosis Factor-α and Toll-Like Receptors in Subclinical Endometritis in Mares. PLoS One 2016;11(5):e0154934.
- Liu H, Wang J, Wang H, Tang N, Li Y, Zhang Y, Hao T. Correlation between matrix metalloproteinase-9 and endometriosis. Int J Clin Exp Pathol 2015;8(10):13399-404.
- Falomo ME, Ferroni L, Tocco I, Gardin C, Zavan B. Immunomodulatory Role of Adipose-Derived Stem Cells on Equine Endometriosis. Biomed Res Int 2015;2015:141485.
- Liu H, Jiang Y, Jin X, Zhu L, Shen X, Zhang Q, Wang B, Wang J, Hu Y, Yan G, Sun H. CAPN 7 promotes the migration and invasion of human endometrial stromal cell by regulating matrix metalloproteinase 2 activity. Reprod Biol Endocrinol 2013 Jul 15;11:64.
- Gaspari G, Funghi F, Cantile C, Camillo F, Panzani D, Maltinti S, Fanelli D, Moroni R, Cremonesi F, Gagni P, Lange-Consiglio A. Amniotic Mesenchymal Stromal/Stem Cell-Derived Extracellular Vesicles for Equine Chronic Degenerative Endometritis Treatment. Vet Med Sci 2026 Mar;12(2):e70685.
- Méndez-Pérez L, Wong YS, Ibáñez BO, Martinez-Hormaza I, Rodríguez-Álvarez L, Castro FO. Bidirectional Interaction Between PGE(2)-Preconditioned Mesenchymal Stem Cells and Myofibroblasts Mediates Anti-Fibrotic Effects: A Proteomic Investigation into Equine Endometrial Fibrosis Reversal. Proteomes 2025 Sep 8;13(3).
- Morawska-Kozłowska M, Pitas M, Zhalniarovich Y. Mesenchymal Stem Cells in Veterinary Medicine-Still Untapped Potential. Animals (Basel) 2025 Apr 19;15(8).
- Piotrowska-Tomala KK, Szóstek-Mioduchowska AZ, Drzewiecka EM, Jonczyk AW, Wójtowicz A, Wrobel MH, Ferreira-Dias G, Skarzynski DJ. Prostaglandin pathways in equine myometrium regulations: endometrosis progression. Front Vet Sci 2024;11:1479508.
- Zdrojkowski Ł, Pawliński B, Skierbiszewska K, Jasiński T, Domino M. Assessment of Connective Tissue in the Equine Uterus and Cervix: Review of Clinical Impact and Staining Options. Animals (Basel) 2024 Jan 3;14(1).
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