Suppression of matrix metalloproteinases inhibits establishment of ectopic lesions by human endometrium in nude mice.

TitleSuppression of matrix metalloproteinases inhibits establishment of ectopic lesions by human endometrium in nude mice.
Publication TypeJournal Article
Year of Publication1997
AuthorsBruner KL, Matrisian LM, Rodgers WH, Gorstein F, Osteen KG
JournalJ Clin Invest
Date Published1997 Jun 15
KeywordsAdult, Animals, Disease Models, Animal, Endometriosis, Endometrium, Estradiol, Female, Glycoproteins, Humans, Metalloendopeptidases, Mice, Mice, Nude, Organ Culture Techniques, Progesterone, Protease Inhibitors, Tissue Inhibitor of Metalloproteinases, Transplantation, Heterologous

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.

Alternate JournalJ Clin Invest
PubMed ID9185507
PubMed Central IDPMC508135
Grant ListHD-28128 / HD / NICHD NIH HHS / United States
HD-30472 / HD / NICHD NIH HHS / United States
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William Rodgers, M.D., Ph.D.

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