Differential regulation of matrix metalloproteinase-3 gene expression in endometriotic lesions compared with endometrium

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 endometria l tissue during the establishment of endometriosis in a rat model. Uteri an d 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 imp lanted in the peritoneum or under the skin, and peritoneal adipose implants were collected at 2 wk, halved, and either frozen or cultured. Gene-specif ic reverse transcriptase-polymerase chain reaction was performed to detect and quantify MMP-2, MMP-3, and TIMP-1 mRNA levels. The peritoneal endometri otic implants progressed from avascularized implants, to vascularized red l esions, to well-established encapsulated cysts. In vivo, MMP-3 mRNA was det ectable 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 tiss ues collected from the intact uterine and from under the skin, at levels si milar to in vivo endometriotic implant MMP-3. In conclusion, ectopic endome trial MMP-3 may participate in the process of invasion and tissue remodelin g that is hypothesized to occur in the pathogenesis of endometriosis.