Cycle-dependent expression of macrophage migration inhibitory factor in the human endometrium

BACKGROUND: Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine that was shown to promote angiogenesis and tissue remodelling. Our previous studies identified MIF as one of the principal bioactive molecules involved in endothelial cell proliferation released by ectopic endometrial cells. METHODS AND RESULTS: In the present study, we examined the expression of MIF in the human endometrium and found an interesting distribution and temporal pattern of expression throughout the menstrual cycle. Immunoreactive MIF was predominant in the glands and surface epithelium. Dual immunofluorescence analysis further identified endothelial cells, macrophages and T-lymphocytes as cells markedly expressing MIF in the stroma. Quantitative assessment of MIF protein showed a regulated cycle phase-dependent expression pattern. MIF expression increased in the late proliferative/early Secretory phase of the menstrual cycle was moderate during the receptive phase or what is commonly called the implantation window before increasing again at the end of the cycle. This pattern paralleled MIF mRNA expression determined by northern blot. CONCLUSION: The cycle phase-specific expression of MIF suggests a tight regulation and perhaps different roles for this factor in the reparative, reproductive and inflammatory-like processes that occur in human endometrium during every menstrual cycle.