Estrogens regulate the release of Macrophage Migration Inhibitory Factor (MIF) by human chorionic villous explants

Aim: hormonal and cytokines factors acting locally at the maternal fetal interface are believed to play a major role in establishing the immune privilege of pregnancy. Numerous studies suggest that estrogens directly affect cellular function including cytokines production. Macrophage Migration Inhibitory Factor (MIF) is a key regulator of the inflammatory and immune responses. We recently demonstrated that MIF is abundantly expressed in first trimester human trophoblast, declined at 11-12 weeks remaining stable until term. Since reports on mice have shown that Estrogens play an important role of macrophage MIF, we investigated the link between Estrogens and the cytokine MIF in human placenta. Methods: chorionic villous explants were exposed to medium containing 17-Estradiol (E2) at concentrations varying from 10-5 to 10-12 M or vehicle alone (Ethanol 0.1%). At 6, 24, 48, hours, tissues supernatants were collected and assayed by ELISA for MIF. Tissues were frozen for assaying MIF expression by western blot analysis and real time PCR. Results: while physiological levels of E2 stimulated MIF release by chorionic villous explans, at higher concentration E2 significantly reduced MIF release in a time dependent manner. No changes were observed in tissues protein and mRNA content. Conclusion: given the crucial role of MIF as potent immunomodulator these findings suggest that Estrogens could play an important role in regulating the levels of released -MIF by the placental site.