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Regular Article |
a Departments of Biochemistry and
b Obstetrics and Gynecology, University of Missouri, Columbia, Missouri 65212
ABSTRACT
In vivo levels of mRNA and the specificity of the extrauterine environment on matrix metalloproteinase (MMP)-3, MMP-2, and tissue inhibitor of matrix metalloproteinase (TIMP)-1 were evaluated in eutopic and ectopic endometrial tissue during the establishment of endometriosis in a rat model. Uteri and endometriotic implants were collected and frozen at 36 h, 2 wk, and 4 wk postsurgery to study in vivo mRNA levels. Intact uteri, uterine tissues implanted in the peritoneum or under the skin, and peritoneal adipose implants were collected at 2 wk, halved, and either frozen or cultured. Gene-specific reverse transcriptase-polymerase chain reaction was performed to detect and quantify MMP-2, MMP-3, and TIMP-1 mRNA levels. The peritoneal endometriotic implants progressed from avascularized implants, to vascularized red lesions, to well-established encapsulated cysts. In vivo, MMP-3 mRNA was detectable at all times in ectopic tissues but not in eutopic uterine tissues, whereas MMP-2 and TIMP-1 were ubiquitously expressed at all times in both tissues. In vitro, only MMP-3 mRNA levels were elevated in endometrial tissues collected from the intact uterine and from under the skin, at levels similar to in vivo endometriotic implant MMP-3. In conclusion, ectopic endometrial MMP-3 may participate in the process of invasion and tissue remodeling that is hypothesized to occur in the pathogenesis of endometriosis.
First decision: 7 September 2000.
1 This research was supported by a University of Missouri-Columbia Molecular Biology Fellowship, a National Institutes of Health predoctoral fellowship to K.E.C., and by support from TAP Holdings, Inc. to K.S.T.
2 Correspondence: Kathy L. Sharpe-Timms, Department of Obstetrics and Gynecology, 1 Hospital Drive, N 625 Health Sciences Center, University of Missouri, Columbia, MO 65212. FAX: 573 882 9010; timmsk{at}health.missouri.edu
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