Endometrial repair is essential for women’s reproductive health and ongoing fertility. Macrophages are essential mediators of tissue repair but we lack fundamental knowledge about how they are regulated in the endometrium. Although there is consensus that macrophages are necessary for repair, their nature, origins and the environmental factors that control their behaviour remain poorly understood thereby limiting our understanding of their function in the endometrium in health and disease.
We have used Csf1r-eGFP transgenic reporter mice in which cells of the monocyte/macrophage lineage are labelled with eGFP (MacGreen) to characterise macrophages during endometrial repair. We have shown that CSF1R+ cells are abundant during endometrial repair and found that monocyte and macrophage subpopulations associate with spatially distinct regions of tissue breakdown and repair ([1]). We performed multiparameter flow cytometry on uterine repair tissues using established subset markers for monocytes and mature macrophages and found that theses populations change dynamically during repair with considerable evidence for heterogeneity within the endometrial macrophage compartment. To investigate this further we performed unbiased profiling of CD45+ cells using single cell RNA sequencing which confirmed the presence of multiple monocyte/macrophage subtypes with potentially distinct ontogenies. Further analysis across distinct time points during endometrial breakdown (12hr), repair (24hr) and remodelling (48hr) identified that endometrial repair was associated with extensive monocyte infiltration and that monocytes supersede tissue resident macrophages during active repair. Notably, infiltrating monocytes expressed key genes associated with tissue repair and were enriched for genes associated with wound healing processes. Following resolution of inflammation, mature macrophages were predominant during endometrial remodelling.
This study offers new insight into the regulation of the endometrial macrophage compartment during endometrial repair and provides a platform for understanding how the phenotype and function of these cells could be dysregulated in women’s reproductive health disorders.