Tubal ectopic pregnancy: macrophages under the microscope

BACKGROUND: Ectopic pregnancy (EP) is a major reproductive health issue, whose underlying causes remain largely unknown. The unusual macrophage presence in the oviduct affected by EP could indicate macrophage contribution to the pathology. METHODS: Macrophages have important functions in reproduction that are reviewed in this work. They are needed for tissue remodelling and immune-regulatory roles, and are present both in the ovary and uterus. Numerous cytokines regulate monocytes recruitment, differentiation and function in the reproductive tract, among them leukaemia inhibitory factor (LIF), colony-stimulating factor 1 and transforming growth factor-beta are indispensable and non-redundant for reproductive outcome. Cytokine types and levels are modulated by estrogen, progesterone and seminal plasma, which drive the differentiation of monocytes to immunity cells or to immunosuppressed trophic and scavenging macrophages. RESULTS: Many risk factors for EP involve an inflammatory reaction that can induce the release of mononuclear phagocytes from the bone marrow and/or favour immunosuppressed trophic differentiation of newly recruited mononuclear phagocytes in the reproductive tract. These observations strengthen the hypothesis that immunosuppressed trophic and scavenging macrophages may have a role in EP onset. CONCLUSIONS: Macrophages may contribute to the regulation of tubal motility through prostaglandin production and induction of progesterone secretion. Considerations about LIF also suggest that macrophages may have a central role in ectopic receptivity.