Abstract
Matrix metalloproteinases of the stromelysin family are expressed in the human endometrium as a consequence of cellular events during the menstrual cycle that require extracellular matrix remodeling. We have recently documented the presence of these enzymes in lesions of endometriosis, a benign disease that presents as persistent ectopic sites of endometrial tissue, usually within the peritoneal cavity. Endometriosis can develop after retrograde menstruation of endometrial tissue fragments, and establishment of ectopic sites within the peritoneal cavity requires breakdown of extracellular matrix. To examine whether matrix metalloproteinases might contribute to the steroid-dependent epidemiology and cellular pathophysiology of endometriosis, we have developed an experimental model of endometriosis using athymic nude mice as recipients of human endometrial tissue. Our results demonstrate that estrogen treatment of human endometrial tissue in organ culture maintains secretion of matrix metalloproteinases, and promotes establishment of ectopic peritoneal lesions when injected into recipient animals. In contrast, suppressing metalloproteinase secretion in vitro with progesterone treatment, or blocking enzyme activity with a natural inhibitor of metalloproteinases, inhibits the formation of ectopic lesions in this experimental model.
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- Aoki D., Katsuki Y., Shimizu A., Kakinuma C., Nozawa S. Successful heterotransplantation of human endometrium in SCID mice. Obstet Gynecol. 1994 Feb;83(2):220–228. [PubMed] [Google Scholar]
- Bergqvist A., Jeppsson S., Kullander S., Ljungberg O. Human uterine endometrium and endometriotic tissue transplanted into nude mice. Morphologic effects of various steroid hormones. Am J Pathol. 1985 Nov;121(2):337–341. [PMC free article] [PubMed] [Google Scholar]
- Bruner K. L., Rodgers W. H., Gold L. I., Korc M., Hargrove J. T., Matrisian L. M., Osteen K. G. Transforming growth factor beta mediates the progesterone suppression of an epithelial metalloproteinase by adjacent stroma in the human endometrium. Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7362–7366. doi: 10.1073/pnas.92.16.7362. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Busiek D. F., Ross F. P., McDonnell S., Murphy G., Matrisian L. M., Welgus H. G. The matrix metalloprotease matrilysin (PUMP) is expressed in developing human mononuclear phagocytes. J Biol Chem. 1992 May 5;267(13):9087–9092. [PubMed] [Google Scholar]
- Carmichael D. F., Sommer A., Thompson R. C., Anderson D. C., Smith C. G., Welgus H. G., Stricklin G. P. Primary structure and cDNA cloning of human fibroblast collagenase inhibitor. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2407–2411. doi: 10.1073/pnas.83.8.2407. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carmichael D. F., Stricklin G. P., Stuart J. M. Systemic administration of TIMP in the treatment of collagen-induced arthritis in mice. Agents Actions. 1989 Jun;27(3-4):378–379. doi: 10.1007/BF01972827. [DOI] [PubMed] [Google Scholar]
- Ishimura T., Masuzaki H. Peritoneal endometriosis: endometrial tissue implantation as its primary etiologic mechanism. Am J Obstet Gynecol. 1991 Jul;165(1):210–214. doi: 10.1016/0002-9378(91)90253-n. [DOI] [PubMed] [Google Scholar]
- Mahmood T. A., Templeton A. Pathophysiology of mild endometriosis: review of literature. Hum Reprod. 1990 Oct;5(7):765–784. doi: 10.1093/oxfordjournals.humrep.a137184. [DOI] [PubMed] [Google Scholar]
- Marbaix E., Kokorine I., Henriet P., Donnez J., Courtoy P. J., Eeckhout Y. The expression of interstitial collagenase in human endometrium is controlled by progesterone and by oestradiol and is related to menstruation. Biochem J. 1995 Feb 1;305(Pt 3):1027–1030. doi: 10.1042/bj3051027. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Martelli M., Campana A., Bischof P. Secretion of matrix metalloproteinases by human endometrial cells in vitro. J Reprod Fertil. 1993 May;98(1):67–76. doi: 10.1530/jrf.0.0980067. [DOI] [PubMed] [Google Scholar]
- Matrisian L. M., Bowden G. T., Krieg P., Fürstenberger G., Briand J. P., Leroy P., Breathnach R. The mRNA coding for the secreted protease transin is expressed more abundantly in malignant than in benign tumors. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9413–9417. doi: 10.1073/pnas.83.24.9413. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Matrisian L. M. The matrix-degrading metalloproteinases. Bioessays. 1992 Jul;14(7):455–463. doi: 10.1002/bies.950140705. [DOI] [PubMed] [Google Scholar]
- Noble L. S., Simpson E. R., Johns A., Bulun S. E. Aromatase expression in endometriosis. J Clin Endocrinol Metab. 1996 Jan;81(1):174–179. doi: 10.1210/jcem.81.1.8550748. [DOI] [PubMed] [Google Scholar]
- Osteen K. G., Bruner K. L., Sharpe-Timms K. L. Steroid and growth factor regulation of matrix metalloproteinase expression and endometriosis. Semin Reprod Endocrinol. 1996 Aug;14(3):247–255. doi: 10.1055/s-2007-1016334. [DOI] [PubMed] [Google Scholar]
- Osteen K. G., Rodgers W. H., Gaire M., Hargrove J. T., Gorstein F., Matrisian L. M. Stromal-epithelial interaction mediates steroidal regulation of metalloproteinase expression in human endometrium. Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):10129–10133. doi: 10.1073/pnas.91.21.10129. [DOI] [PMC free article] [PubMed] [Google Scholar]
- RIDLEY J. H., EDWARDS I. K. Experimental endometriosis in the human. Am J Obstet Gynecol. 1958 Oct;76(4):783–790. doi: 10.1016/0002-9378(58)90011-5. [DOI] [PubMed] [Google Scholar]
- Ray J. M., Stetler-Stevenson W. G. The role of matrix metalloproteases and their inhibitors in tumour invasion, metastasis and angiogenesis. Eur Respir J. 1994 Nov;7(11):2062–2072. [PubMed] [Google Scholar]
- Rodgers W. H., Matrisian L. M., Giudice L. C., Dsupin B., Cannon P., Svitek C., Gorstein F., Osteen K. G. Patterns of matrix metalloproteinase expression in cycling endometrium imply differential functions and regulation by steroid hormones. J Clin Invest. 1994 Sep;94(3):946–953. doi: 10.1172/JCI117461. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rodgers W. H., Osteen K. G., Matrisian L. M., Navre M., Giudice L. C., Gorstein F. Expression and localization of matrilysin, a matrix metalloproteinase, in human endometrium during the reproductive cycle. Am J Obstet Gynecol. 1993 Jan;168(1 Pt 1):253–260. doi: 10.1016/s0002-9378(12)90922-9. [DOI] [PubMed] [Google Scholar]
- Salamonsen L. A. Matrix metalloproteinases and endometrial remodelling. Cell Biol Int. 1994 Dec;18(12):1139–1144. doi: 10.1006/cbir.1994.1040. [DOI] [PubMed] [Google Scholar]
- Schatz F., Papp C., Toth-Pal E., Lockwood C. J. Ovarian steroid-modulated stromelysin-1 expression in human endometrial stromal and decidual cells. J Clin Endocrinol Metab. 1994 Jun;78(6):1467–1472. doi: 10.1210/jcem.78.6.8200951. [DOI] [PubMed] [Google Scholar]
- Sillem M., Hahn U., Coddington C. C., 3rd, Gordon K., Runnebaum B., Hodgen G. D. Ectopic growth of endometrium depends on its structural integrity and proteolytic activity in the cynomolgus monkey (Macaca fascicularis) model of endometriosis. Fertil Steril. 1996 Sep;66(3):468–473. doi: 10.1016/s0015-0282(16)58521-5. [DOI] [PubMed] [Google Scholar]
- Spuijbroek M. D., Dunselman G. A., Menheere P. P., Evers J. L. Early endometriosis invades the extracellular matrix. Fertil Steril. 1992 Nov;58(5):929–933. doi: 10.1016/s0015-0282(16)55437-5. [DOI] [PubMed] [Google Scholar]
- TE LINDE R. W., SCOTT R. B. Experimental endometriosis. Am J Obstet Gynecol. 1950 Nov;60(5):1147–1173. doi: 10.1016/0002-9378(50)90517-5. [DOI] [PubMed] [Google Scholar]
- Zamah N. M., Dodson M. G., Stephens L. C., Buttram V. C., Jr, Besch P. K., Kaufman R. H. Transplantation of normal and ectopic human endometrial tissue into athymic nude mice. Am J Obstet Gynecol. 1984 Jul 15;149(6):591–597. doi: 10.1016/0002-9378(84)90240-0. [DOI] [PubMed] [Google Scholar]