Macrophages: an indispensable piece of ovarian health

Macrophages are the most abundant immune cells in the ovary. In addition to their roles in the innate immune system, these heterogeneous tissue-resident cells are responsive to tissue-derived signals, adapt to their local tissue environment, and specialize in unique functions to maintain tissue homeostasis. Research in the past decades has established a strong link between macrophages and various aspects of ovarian physiology, indicating a pivotal role of macrophages in ovarian health. However, unlike other intensively studied organs, the knowledge of ovarian macrophages dates back to the time when the heterogeneity of ontogeny, phenotype, and function of macrophages was not fully understood. In this review, we discuss the evolving understanding of the biology of ovarian tissue-resident macrophages, highlight their regulatory roles in normal ovarian functions, review the association between certain ovarian pathologies and disturbed macrophage homeostasis, and finally, discuss the technologies that are essential for addressing key questions in the field.