These mice are depleted of circulating monocytes and tissue macrophages in several organs, including the uterus. They experience severely reduced fertility, lower implantation rates, and greater embryonic wastage compared with wild-type females. Paradoxically, excess decidual macrophage infiltration has been linked to preeclampsia and intrauterine growth restriction in humans.
Macrophage migration inhibitory factor (MIF) is a 12.5-kDa cytokine that inhibits the migration and chemotaxis of macrophages. High steady-state levels of MIF mRNA and protein have been detected in human reproductive tissues. MIF expression has been reported in the follicular fluid and granulosa cells of the human ovary. The presence of MIF in embryonic and maternal tissues has been documented in previous studies conducted by our group. In first trimester human placentas, we have detected MIF in the cytotrophoblasts of both the inner layer of the villi and in the trophoblastic cell islands. More recently, we have demonstrated the presence of MIF in the glandular and stromal compartments of cycling endometrium, as well as in first trimester decidua.