Evidence for a dynamic role for mononuclear phagocytes during endometrial repair and remodelling

In women, endometrial breakdown, which is experienced as menstruation, is characterised by high concentrations of inflammatory mediators and immune cells which account for ~40% of the stromal compartment during tissue shedding. These inflammatory cells are known to play a pivotal role in tissue breakdown but their contribution to the rapid scarless repair of endometrium remains poorly understood. In the current study we used a mouse model of menstruation to investigate dynamic changes in mononuclear phagocytes during endometrial repair and remodelling. Menstruation was simulated in MacGreen mice to allow visualisation of CSF1R⁺ mononuclear phagocytes. Immunohistochemistry revealed dynamic spatio-temporal changes in numbers and location of CSF1R-EGFP⁺ cells and Ly6G⁺ neutrophils. Flow cytometry confirmed a striking increase in numbers of GFP⁺ cells during repair (24 h): influxed cells were 66% F4/80⁺Gr-1⁺ and 30% F4/80^-Gr-1⁺. Immunostaining identified distinct populations of putative 'classical' monocytes (GFP⁺F4/80^-), monocyte-derived macrophages (GFP⁺F4/80⁺) and a stable population of putative tissue-resident macrophages (GFP^-F4/80⁺) localised to areas of breakdown, repair and remodelling respectively. Collectively, these data provide the first compelling evidence to support a role for different populations of monocytes/macrophages in endometrial repair and provide the platform for future studies on the role of these cells in scarless healing.