Abstract: 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 during active repair but that mature macrophages were predominant during endometrial remodelling following resolution of inflammation.

These studies offer new insights into the regulation of the endometrial macrophage compartment during endometrial repair and provide a platform for understanding how the phenotype and function of these cells could be dysregulated in women’s reproductive health disorders.

[1] Cousins, F.L., Kirkwood, P.M., Saunders, P.T.K. & Gibson D.A. Evidence for a dynamic role for mononuclear phagocytes during endometrial repair and remodelling. Sci Rep 6, 36748 (2016). https://doi.org/10.1038/srep36748

Biography: Dr Douglas Gibson is a Principal Investigator & Sir Henry Dale Fellow in the Centre for Inflammation Research at the University of Edinburgh. His research focuses on understanding how hormones control immune cell function in the womb and how this might affect women's reproductive health. His lab uses fate-mapping techniques, transcriptomics analysis, multiparameter flow cytometry and immunohistochemistry in order to characterise the phenotype and function of immune cell populations that are required for endometrial repair and remodelling. He is the recipient of the Wellcome-Beit Prize, Society for Reproduction and Fertility New Investigator Award and the Society for Endocrinology Early Career Prize lecture.