Dynamics and Regulation of Maternal–Fetal Interface Macrophages: From Immune Tolerance to Pregnancy Outcomes

ABSTRACT The fetal–maternal interface is a uniquely active immune niche that must continuously balance tolerance of a semi‑allogeneic fetus with competent antimicrobial defense. Within this setting, macrophages are central innate sentinels whose phenotypes and functions are highly flexible, and this plasticity is increasingly viewed as a key determinant of normal gestation. During a successful pregnancy, they help maintain local immunity by promoting the resolution of inflammation, remodeling tissues, and supporting angiogenesis. By contrast, pregnancy complications—including miscarriage and preterm birth—often feature skewed macrophage polarization and loss of function, pointing to a contributory pathogenic role. Despite abundant work describing stage‐specific activities, the signaling circuits that program macrophage behavior, their subset diversification, and their crosstalk with other immune cells remain incompletely mapped. This review summarizes the cellular composition and temporal shifts of the fetal–maternal immune milieu, integrates current data on macrophage localization and regulation, and outlines how their dysregulation may drive disease, to frame mechanistic hypotheses and highlight therapeutic targets.