The Role of Macrophages in Endometrial Cyclical Changes and Female Reproductive System Diseases: A Review

Background: This review aims to systematically summarize the lineage origins, subtype classification, and functional dynamics of endometrial macrophages, clarify their mechanisms of action in normal reproductive physiology (menstrual cycle, pregnancy) and common reproductive diseases, integrate cognitive breakthroughs brought by cutting-edge research technologies, and provide theoretical support for basic research and clinical translation in reproductive medicine. Methods: Recent basic and clinical research studies related to endometrial macrophages were retrieved, with a focus on incorporating findings from technologies such as single-cell sequencing and multi-omics. The reviewed content covers core aspects including macrophage origins (embryonic-derived, bone marrow-derived), subtype classification (M1/M2 and novel metabolism-related subtypes), cycle- and pregnancy-specific functions, and disease-associated mechanisms. A comprehensive analysis of the regulatory networks of endometrial macrophages under physiological and pathological conditions was conducted. Results: Endometrial macrophages, by virtue of their phenotypic plasticity and functional heterogeneity, play a central role in cyclical endometrial remodeling, pregnancy establishment, and the regulation of reproductive immune homeostasis. Dysregulation of their function is closely associated with various reproductive disorders such as recurrent spontaneous abortion and endometriosis. In-depth exploration of their biological characteristics and regulatory mechanisms holds great significance for filling knowledge gaps in the field of reproductive immunology and advancing precise prevention and treatment of related diseases. Conclusions: Endometrial macrophages are core regulators of the reproductive immune microenvironment, and their spatiotemporal dynamic functions are closely linked to reproductive health. The revelation of novel classification systems and regulatory mechanisms provides new perspectives for in-depth understanding of reproductive physiological and pathological processes, as well as important targets for immune-targeted therapy of reproductive-related diseases. This holds great clinical translational significance for promoting the precision development of reproductive medicine.