Department of Obstetrics and Gynecology, University of Missouri-Columbia, Columbia, Missouri 65212, USA
Address for correspondence: K. L. Sharpe-Timms, Department of Obstetrics and Gynecology, University of Missouri-Columbia, 1 Hospital Drive, Columbia, MO 65212. Voice: 573-882-7937; fax: 573-882-9010.
timmsk{at}health.missouri.edu
Following retrograde menstruation, shed endometrial tissue fragments
attach to and invade the peritoneal surface to form established
endometriotic lesions. With disease progression, the biochemically
active lesions undergo remodeling and become fibrotic. Matrix
metalloproteinase enzymes (MMPs) and the tissue inhibitors of
metalloproteinases (TIMPs) play a significant role in normal
endometrial remodeling during menses. Anomalous expression of
MMPs and TIMPs has been identified in endometriotic lesions
as compared to their highly regulated expression in eutopic
endometrium. The paracrine mechanisms regulating misexpression
of MMPs and TIMPs by endometriotic lesions are, however, not
well defined. Misexpression of the MMPs and TIMPs may be due
to innate anomalies in the eutopic endometrium from women with
endometriosis, in the resident immune cells and peritoneal cells
that juxtapose the ectopic endometrium, and/or numerous substances
present in peritoneal fluid of women with endometriosis. The
majority of MMPs are under strict transcriptional regulation.
Steroid hormones and cytokines appear to act on the MMP promoter,
either independently or in consort, to provide both positive
and negative regulation of these genes. Misregulated expression
of MMPs and TIMPs is associated with a more aggressive phenotype
and a cascade of events facilitating peritoneal extracellular
matrix degradation and establishment or remodeling of endometriotic
lesions. The mechanisms by which MMP and TIMP expression are
misregulated warrant further investigation as such information
may provide insight into novel therapeutic modalities for endometriosis.
