Women's Reproductive Health Research Center, Department of Obstetrics and Gynecology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
Address for correspondence: Kevin G. Osteen, Ph.D., Director, Women's Reproductive Health Research Center, B-1100 Medical Center North, Department of Obstetrics and Gynecology, Vanderbilt University School of Medicine, Nashville, TN 37232. Voice: 615-322-4196; fax: 615-343-7913.
kevin.osteen{at}mcmail.vanderbilt.edu
The human endometrium exhibits regular cycles of growth, differentiation,
and breakdown in response to changing levels of ovarian steroids.
Following the tissue loss and repair processes of menstruation,
rising levels of estradiol initiate a development-like process
leading to a complete restructuring of the endometrial surface.
In contrast, while under the predominate influence of progesterone,
proliferation declines as cell-specific differentiation prepares
the endometrium for pregnancy over a 5- to 6-day period. In
the absence of nidation, steroid support is lost; the endometrial
surface begins a complex process of tissue breakdown and bleeding,
producing a viscous mixture of cellular debris within a bloody
menstrual effluent. Although most of the menstrual fluid exits
the body, reflux of some material occurs in most women, providing
a poorly understood opportunity for ectopic endometrial growth
and establishment of the disease endometriosis. The cyclic restructuring
of the endometrium requires numerous matrix metalloproteinases
(MMPs) that mediate normal and pathological tissue turnover
throughout the reproductive tract. The expression of multiple
MMPs facilitates degradation of extracellular matrix during
growth-related remodeling as well as tissue breakdown at the
time of menstruation. However, these enzymes are absent during
the early and midsecretory phase and the suppression of endometrial
MMPs remains important to maintaining the integrity of the endometrium
during the highly invasive events required to establish a normal
hemochorial placenta. Several research groups have suggested
that steroid-mediated expression and action of MMPs during the
menstrual cycle may provide a key mechanistic link between endometrial
turnover and the invasive processes necessary for establishment
of endometriosis.
