173. ENDOMETRIAL REPAIR – ENTER THE MATRIX

Abstract

Menstruation and endometrial repair are two opposing functions which occur simultaneously within the menstruating uterus. Whilst the factors that control menstruation are increasingly understood¹ 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 integrins². We have utilised two models of endometrial repair, a mouse menstruation model³, and an endometrial luminal epithelial cell-line (ECC-1)⁴ with the aim of defining the adhesion and ECM molecules important for endometrial repair. Uterine horns (repairing and non-repairing control from each of 4 mice) were subjected to laser-capture microdissection of the repairing luminal epithelium (LE) and immediate sub-luminal stroma. RNA was extracted and processed for pathway-focused array. ECC-1 cells were grown to over-confluence, wounded and allowed to repair. RNA was extracted on each day during repair and used for oligo-microarray analysis. Menstruating/repairing human endometrium was investigated for expression of ECM molecules by immunohistochemistry.A host of ECM molecules (ADAMTS's, MMP's, cadherins, integrins and matrix proteins) were shown to be altered in the repairing murine endometrium. In agreement with published data², fibronectin and integrins α5 and β1 were elevated at the time of repair. However, in our models, fibronectin was regulated mainly in the stromal compartment, demonstrated by its absence in the ECC-1 model and concentrated stromal immunolocalization in human endometrium. Both integrins displayed regulated expression in the ECC-1 model and localised to repairing LE of human endometrium. Other noteworthy ECM molecules regulated solely within the murine model include integrins (αM, αL, β2) and selectins expressed on lymphocytes, which may reflect the importance of these cells in endometrial repair⁵. In conclusion, these data suggest the ECM contributes to the dynamic changes observed during endometrial repair and these models may enable further insight into the roles of each cellular compartment.