Introduction: The endometrium is one of the few adult tissues that heals repeatedly without scarring. On a monthly basis the endometrium undergoes cyclical episodes of proliferation, degeneration, tissue repair and remodelling in response to the injury inflicted on it during menstruation. In women, endometrial shedding (menses) is the culmination of a cascade of inflammatory signals between uterine stromal cells and immune cells both of which have key roles in endometrial breakdown and repair. In mice, we can induce endometrial shedding and replicate rapid, scar-free healing of the endometrial lining (Cousins et al2014 PLOS ONE). Inflammatory cells play an essential role in tissue breakdown during menses but their role in repair and restoration of tissue homeostasis remains poorly understood. In the current study we investigated immune cell dynamics during endometrial repair and remodelling.
Methods: Menstruation was simulated in vivo in MacGreen® mice, in which cells of the mononuclear phagocyte system express GFP, in order to investigate dynamic changes in immune cell populations during post menstrual endometrial repair and remodelling (8, 24, 48 h after removal of progesterone). Uterine horns were collected for flow cytometry or fixed frozen for immunohistochemistry. Tissue distribution of immune cells was determined by immunohistochemistry GFP+ cell populations were analysed by Flow Cytometry.
Results and Discussion: Immunohistochemistry demonstrated striking spatio-temporal changes in numbers and location of GFP+ cells during endometrial breakdown and repair which peaked 24 h after removal of progesterone. Flow Cytometry revealed a significant influx of GFP+ cells during repair the majority of which were characterised as Gr-1+F4/80+. These data provide the first compelling evidence to support a dynamic role for inflammatory monocytes in endometrial repair and provide the platform for future studies on the role of these cells in scarless healing. (Supported by MRC programme grant to PTKS and an MRC Doctoral Training Grant to PMK).
11 Jul 2016 - 11 Jul 2016