159. EXTRACELLULAR MATRIX DYNAMICS IN SCAR-FREE ENDOMETRIAL REPAIR
J. Evans A , T. Kaitu’u-Lino B and L. A. Salamonsen AA Prince Henry’s Institute of Medical Research, Clayton, VIC, Australia.
B Obstetrics and Gynaecology, Monash University, Clayton, VIC, Australia.
Reproduction, Fertility and Development 22(9) 77-77 https://doi.org/10.1071/SRB10Abs159
Published: 6 September 2010
Abstract
Tissue destruction and repair occur simultaneously within the menstruating uterus. Whilst the factors that control menstruation are increasingly understood (1) the endometrial milieu which governs repair remains elusive. The extracellular-matrix (ECM) plays a dynamic role within the repairing endometrium, with roles suggested for fibronectin and certain integrins (2). We here use both an in vivo mouse model of breakdown and repair (3) and an in vitro model of re-epithelialisation to determine factors involved in repair of this tissue. Murine uterine horns were subjected to laser-capture microdissection of the repairing luminal epithelium (LE) and immediate sub-luminal stroma. Extracted RNA was processed for pathway-focused array that revealed expression of epithelial and leukocyte expressed integrins along with their ligands, proteases and protease inhibitors and basement membrane proteins as elevated in repairing uterine horns. Immunohistochemistry confirmed expression and localisation of integrins a 5 and b 1 in addition to integrin ligands VCAM-1 and fibronectin. Additionally, we demonstrated intimate association of neutrophils with repairing/recently repaired luminal epithelium. To confirm the relevance of these ECM interactions in a human model, human endometrial luminal epithelial cell (ECC-1) monolayers were wounded and treated with inhibitors of MMPs (doxycycline, GM6001) or integrin-fibronectin interactions (RGDS). Significant inhibition of in vitro re-epithelialisation was seen following treatment of wounded ECC-1 monolayers with RGDS, doxycycline or GM6001, suggesting a requirement for these ECM components in endometrial re-epithelialisation. We subsequently demonstrated that menstrual blood derived factors may play a role in the initial endometrial re-epithelialisation. Menstrual blood and peripheral blood were collected on the same day from volunteers. Treatment of wounded ECC-1 monolayers with menstrual blood plasma enhanced the rate of repair compared with peripheral blood plasma from the same woman. Enhanced understanding of the mechanisms governing scar-free repair in the endometrium may help resolve pathological endometrial bleeding disorders and may be applied to aid healing in other tissues.
(1) Jabbour et al, 2006. Endocr Rev. 27(1): 17–46.
(2) Cao et al, 2007. Hum Reprod. 22(12): 3223–31
(3) Brasted et al, 2003. Biol Reprod. 69(4): 1273–80.
