Multimodal Profiling of Repair-Associated Immune Dynamics in a Mouse Model of Menstruation

Abstract

Despite the importance of inflammation to menstruation, we lack detailed understanding of how immune dynamics contribute to endometrial repair. We performed detailed phenotypic characterisation of uterine immune cells using single cell RNA sequencing, flow cytometry and multiplex immunohistochemistry in a mouse model of simulated menstruation. Uterine tissues were collected from age-matched controls or from key phases of menstruation, including tissue breakdown, repair and remodelling. Our findings reveal distinct compositional changes across different phases of menstruation and highlight predominant roles for monocytes, macrophages, and neutrophils in endometrial repair. Immunohistochemistry revealed the spatial association of these myeloid cell subsets with areas of tissue repair and remodelling. Bioinformatic analysis highlighted key roles for monocyte, macrophage and neutrophil signalling during endometrial repair with thrombospondin 1 and secreted phosphoprotein 1 emerging as key signalling pathways. These data significantly advance our understanding of menstrual physiology and identify potential therapeutic targets for menstrual disorders. summaryThis study investigates immune cell dynamics in a mouse model of menstruation, highlighting roles for monocytes, macrophages, and neutrophils in non-fibrotic endometrial repair, and identifies key signalling pathways as potential therapeutic targets for menstrual disorders.