Macrophage Migration Inhibitory Factor in the Human Endometrium: Expression and Localization During the Menstrual Cycle and Early Pregnancy1

Abstract

Macrophage migration inhibitory factor (MIF) was discovered as an activated T-lymphocyte-derived protein that inhibits the random migration of macrophages in vitro. Subsequently, knowledge of the physiological actions of MIF was extended to include its role as a proinflammatory cytokine that affects several functions of macrophages and lymphocytes. Previous reports have suggested an involvement of MIF in reproduction. However, no data are currently available on the presence of this cytokine in the human endometrium. In this study, the expression and tissue localization of MIF was evaluated in specimens of cycling endometrium, first trimester placenta bed biopsy, and isolated endometrial glands by Western blot analysis, immunohistochemistry, ELISA, and reverse transcription-polymerase chain reaction. The results demonstrated that MIF is expressed in human endometrium across the menstrual cycle and in early pregnancy. Immunohistochemical localization identified the protein in glandular epithelium, in stromal and predecidualized stromal cells of cycling endometrium, as well as in the decidua of first-trimester placenta. The proinflammatory features and specific actions of MIF on lymphoid cells suggest its potential involvement in several aspects of endometrial physiology.

Human decidual natural killer cells as a source and target of macrophage migration inhibitory factor

“…In the first trimester human placenta, MIF has been detected in the cytotrophoblasts of both the inner layer of villi and in the trophoblastic cell islands (Arcuri et al 1999). More recently, we have shown that this cytokine is expressed in the glandular and stromal compartment of cyclic endometrium, as well as in first trimester decidua (Arcuri et al 2001). Because of this, and in keeping with its immunomodulatory functions, we have suggested a role for MIF in modulating uNK cell activity (Arcuri et al 2001).…”

“…More recently, we have shown that this cytokine is expressed in the glandular and stromal compartment of cyclic endometrium, as well as in first trimester decidua (Arcuri et al 2001). Because of this, and in keeping with its immunomodulatory functions, we have suggested a role for MIF in modulating uNK cell activity (Arcuri et al 2001). The study reported herein was undertaken to test this hypothesis.…”

Uncoupling Protein 2, but Not Uncoupling Protein 1, Is Expressed in the Female Mouse Reproductive Tract

“…In the endometrium, macrophages represent an important mechanism of defense, including the degradation of cellular debris in endometrial shedding and repair and protection against infections. However, the mechanisms involved in recruiting, maintaining, and activating uterine macrophages are not fully defined (41)(42)(43). In situ hybridization has shown that the expression of UCP2 in the uterus is restricted to the endometrium, especially in epithelial cells and uterine glands.…”

Serum macrophage migration inhibitory factor in the prediction of preterm delivery

“…9-11 MIF is expressed in the human ovary, endometrial cells, 1 st trimester trophoblasts, reflected fetal membranes, and chorioamniotic membranes at delivery. [12][13][14][15][16] In addition, soluble MIF is present in amniotic fluid, maternal blood, umbilical cord blood, and the intervillous circulation of the placenta. 15, 17-20 Consistent in its role as mediator of innate immunity and inflammation, MIF is induced in various infections, including those that occur during pregnancy.…”