The Role of the Matrisome in Endometriosis Development

PROJECT SUMMARY/ABSTRACT:
Endometriosis is a gynecological disease resulting from abnormal growth of endometrial tissue outside the
uterine cavity. This disease causes chronic pain, extreme pain with menstruation, and/or infertility in at least 7.4
million American women per year. The annual cost burden exceeds $70 billion and no cure or effective
treatments exist. A common therapy is the suppression of ovarian estrogen production, but upon cessation of
treatment >70% of women report symptomatic disease. Women with endometriosis have increased immune cells
in their peritoneal cavity and often have higher incidences of autoimmune disorders; however, the pathogenesis
of endometriosis remains poorly understood. Data from our mouse model of endometriosis, in which donor
uterine tissue is freely dispersed into the peritoneal cavity of an immunocompetent host, has uncovered that
initiation of endometriosis is dependent on the immune system. These data from our mouse model strongly
correlate with alterations seen in women. Our long-term goal is to contribute toward the development of
mechanism-based strategies to prevent, diagnose, and/or treat endometriosis. The objective in this proposal is
to determine the role of neutrophil and macrophage mediated signaling on uterine tissue attachment during the
immune-dependent phase of endometriosis. Therefore, we hypothesize the crosstalk among uterine cells, PMNs,
and MΦs in women with EMS secrete matrisome and matrisome associated factors that promote and support
EMS lesion establishment. The following aims are designed to test this hypothesis: Aim 1 will identify the
neutrophil population and characterize how their secreted signaling molecules contribute to endometriosis
lesion attachment. Aim 2 will identify the macrophage population and characterize how secreted signaling
molecules contribute to endometriosis lesion survival. Aim 3 will uncover key matrisome factors that induce
uterine tissue to form EMS lesions in vitro and in vivo. At the successful completion of this proposed research,
the results are expected to have an important positive impact on the understanding of endometriosis. The data
will contribute substantively to a mechanism based framework to elucidate endometriosis disease initiation that
will, in turn, provide new opportunities for identifying targets for the development of novel therapeutics.

Grant Number: 5R01HD097597-05
NIH Institute/Center: NIH
Principal Investigator: Katherine Burns