This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhang, J. Articles by Salamonsen, L. A. Search for Related Content PubMed PubMed Citation Articles by Zhang, J. Articles by Salamonsen, L. A.

In Vivo Evidence for Active Matrix Metalloproteinases in Human Endometrium Supports their Role in Tissue Breakdown at Menstruation

Prince Henry’s Institute of Medical Research, Clayton, Victoria 3168, Australia

Address all correspondence and requests for reprints to: Lois A Salamonsen, Associate Professor, Prince Henry’s Institute of Medical Research, P.O. Box 5152, Clayton, Victoria 3168, Australia. E-mail: . lois.salamonsen{at}med.monash.edu.au

Abstract

Human endometrium remodels extensively during each reproductive cycle culminating in loss of most functionalis tissue at menstruation. Evidence suggests that menstruation results from the action of the matrix metalloproteinases (MMP), enzymes secreted in latent forms. MMP activation is thus an important regulatory step. It has not been established that MMPs are active within menstrual endometrium in vivo. We used in situ zymography to demonstrate active forms of MMPs in human endometrium across the normal menstrual cycle. Both gelatinase and collagenase activities were detected in most endometrial tissues. Semiquantitation demonstrated a substantial and significant increase in both gelatinase and collagenase activity in menstrual samples compared with those at any other time of the cycle. Gelatinase activity was both associated with cells and extracellular. All collagenase activity was extracellular. Immunoreactive MMP-2 and MMP-9 colocalized with active gelatinase, although much immunoreactive gelatinase was inactive. Some gelatinase activity colocalized with CD45⁺ leukocytes. Menstruation is initiated at discrete foci, and active MMPs were similarly at foci within the tissue. This is the first in vivo evidence for increased active MMPs in menstrual endometrium compared with other stages of the cycle. These findings position the MMPs for a critical role in the matrix degradation at menstruation.

This article has been cited by other articles:

				I. M. Porto, L. B. Rocha, M. A. Rossi, and R. F. Gerlach In Situ Zymography and Immunolabeling in Fixed and Decalcified Craniofacial Tissues J. Histochem. Cytochem., July 1, 2009; 57(7): 615 - 622. [Abstract] [Full Text] [PDF]

				S. D. Smith, C. E. Dunk, J. D. Aplin, L. K. Harris, and R. L. Jones Evidence for Immune Cell Involvement in Decidual Spiral Arteriole Remodeling in Early Human Pregnancy Am. J. Pathol., May 1, 2009; 174(5): 1959 - 1971. [Abstract] [Full Text] [PDF]

				J.L. Brun, C. Galant, D. Delvaux, P. Lemoine, P. Henriet, P.J. Courtoy, and E. Marbaix Menstrual activity of matrix metalloproteinases is decreased in endometrium regenerating after thermal ablation Hum. Reprod., February 1, 2009; 24(2): 333 - 340. [Abstract] [Full Text] [PDF]

				S. Labied, C. Galant, M. Nisolle, S. Ravet, C. Munaut, E. Marbaix, J.-M. Foidart, and F. Frankenne Differential elevation of matrix metalloproteinase expression in women exposed to levonorgestrel-releasing intrauterine system for a short or prolonged period of time Hum. Reprod., January 1, 2009; 24(1): 113 - 121. [Abstract] [Full Text] [PDF]

				N. B Morison, J. Zhang, T. J Kaitu'u-Lino, I. S Fraser, and L. A Salamonsen The long-term actions of etonogestrel and levonorgestrel on decidualized and non-decidualized endometrium in a mouse model mimic some effects of progestogen-only contraceptives in women Reproduction, January 1, 2007; 133(1): 309 - 321. [Abstract] [Full Text] [PDF]

				M. Hickey, J. Crewe, L. A. Mahoney, D. A. Doherty, I. S. Fraser, and L. A. Salamonsen Mechanisms of Irregular Bleeding with Hormone Therapy: The Role of Matrix Metalloproteinases and Their Tissue Inhibitors J. Clin. Endocrinol. Metab., August 1, 2006; 91(8): 3189 - 3198. [Abstract] [Full Text] [PDF]

				S. Malik, K. Day, I. Perrault, D.S. Charnock-Jones, and S. K. Smith Reduced levels of VEGF-A and MMP-2 and MMP-9 activity and increased TNF-{alpha} in menstrual endometrium and effluent in women with menorrhagia Hum. Reprod., August 1, 2006; 21(8): 2158 - 2166. [Abstract] [Full Text] [PDF]

				B. J. Gu and J. S. Wiley Rapid ATP-induced release of matrix metalloproteinase 9 is mediated by the P2X7 receptor Blood, June 15, 2006; 107(12): 4946 - 4953. [Abstract] [Full Text] [PDF]

				T. J. Kaitu'u, J. Shen, J. Zhang, N. B. Morison, and L. A. Salamonsen Matrix Metalloproteinases in Endometrial Breakdown and Repair: Functional Significance in a Mouse Model Biol Reprod, October 1, 2005; 73(4): 672 - 680. [Abstract] [Full Text] [PDF]

				P. B. Cornet, C. Galant, Y. Eeckhout, P. J. Courtoy, E. Marbaix, and P. Henriet Regulation of Matrix Metalloproteinase-9/Gelatinase B Expression and Activation by Ovarian Steroids and LEFTY-A/Endometrial Bleeding-Associated Factor in the Human Endometrium J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 1001 - 1011. [Abstract] [Full Text] [PDF]

				C. Galant, M. Berliere, D. Dubois, J.-C. Verougstraete, A. Charles, P. Lemoine, I. Kokorine, Y. Eeckhout, P. J. Courtoy, and E. Marbaix Focal Expression and Final Activity of Matrix Metalloproteinases May Explain Irregular Dysfunctional Endometrial Bleeding Am. J. Pathol., July 1, 2004; 165(1): 83 - 94. [Abstract] [Full Text] [PDF]

				W. M. Frederiks and O. R.F. Mook Metabolic Mapping of Proteinase Activity with Emphasis on In Situ Zymography of Gelatinases: Review and Protocols J. Histochem. Cytochem., June 1, 2004; 52(6): 711 - 722. [Abstract] [Full Text] [PDF]

				L. T. Goldsmith, G. Weiss, S. Palejwala, T. M. Plant, A. Wojtczuk, W. C. Lambert, N. Ammur, D. Heller, J. H. Skurnick, D. Edwards, et al. Relaxin regulation of endometrial structure and function in the rhesus monkey PNAS, March 30, 2004; 101(13): 4685 - 4689. [Abstract] [Full Text] [PDF]

				Y. Noguchi, T. Sato, M. Hirata, T. Hara, K. Ohama, and A. Ito Identification and Characterization of Extracellular Matrix Metalloproteinase Inducer in Human Endometrium during the Menstrual Cycle in Vivo and in Vitro J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 6063 - 6072. [Abstract] [Full Text] [PDF]

				S. J. Yan and E. A. G. Blomme In Situ Zymography: A Molecular Pathology Technique to Localize Endogenous Protease Activity in Tissue Sections Vet. Pathol., May 1, 2003; 40(3): 227 - 236. [Abstract] [Full Text] [PDF]

				C.-S. Chou, C.-J. Tai, C. D. MacCalman, and P. C. K. Leung Dose-Dependent Effects of Gonadotropin Releasing Hormone on Matrix Metalloproteinase (MMP)-2, and MMP-9 and Tissue Specific Inhibitor of Metalloproteinases-1 Messenger Ribonucleic Acid Levels in Human Decidual Stromal Cells in Vitro J. Clin. Endocrinol. Metab., February 1, 2003; 88(2): 680 - 688. [Abstract] [Full Text] [PDF]