Macrophages: a double-edged sword in female reproduction and disorders

Abstract

Reproduction consists of sequential inflammation-like events, primarily within the endometrium, from ovulation to embryo implantation, decidualization and delivery. During the reproductive cycle, the endometrium repeatedly undergoes cyclic periods of proliferation, differentiation, tissue breakdown and repair without scarring. Owing to their phagocytic activity, macrophages, key players in innate immunity, are thought to play crucial roles in the endometrium. Endometrial macrophages actively participate in various stages of reproductive tissue remodeling, particularly during decidualization and pregnancy establishment. Traditionally considered simple bystanders that clear debris to prevent autoimmune responses in tissue homeostasis, macrophages are now recognized as main actors with broad functional plasticity that allows them to fine tune the balance between pro- and anti-inflammatory responses during tissue inflammation, remodeling and repair. Homeostatic balance is determined by the sum of various mediators produced by two distinctly polarized macrophage subpopulations. The biased polarization of tissue-resident macrophages may contribute to the pathogenesis of various diseases, such as inflammation and cancer. Thus, understanding how macrophages contribute to endometrial homeostasis is crucial for deciphering the underlying mechanisms of various reproductive disorders. Nanomedicines using extracellular vesicles, nanoparticles and noncoding RNAs have recently been applied to modulate macrophage polarization and alleviate disease phenotypes. Despite these advances, the functions of endometrial macrophages under physiological and pathophysiological conditions remain poorly understood, which complicates the development of targeted therapies. Here we update the current understanding of the homeostatic function of macrophages and the putative contribution of endometrial macrophage dysfunction to reproductive disorders in women, along with innovative molecular therapeutics to resolve this issue. Macrophages are a type of white blood cell that plays a key role in our immune system by engulfing and digesting harmful substances. This Review explores the diverse roles of macrophages beyond their basic immune functions, particularly in female reproduction. Researchers found that these cells are crucial for inflammation regulation and tissue repair. Macrophages can change their behavior based on signals from their environment, which is known as polarization. They can become either M1 or M2 types, depending on the situation. In female reproduction, macrophages help with processes such as menstruation, embryo implantation and pregnancy maintenance. The study concludes that understanding macrophage functions can lead to new treatments for reproductive issues. Future research may focus on using macrophage-targeted therapies to improve reproductive health and treat related diseases. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.