Abstract
Macrophage Migration Inhibitory Factor (MIF) is a multifunctional molecule highly secreted by human placenta mainly in the early phases of pregnancy. Studies in different cells show that MIF is a pro-survival factor by binding to its receptor CD74. By using the in vitro model of placental explants from first trimester pregnancy, we investigated the role of MIF in the survival of placental cells under induced stress conditions that promote apoptosis or mimic the hypoxia/re-oxygenation (H/R) injury that placenta could suffer in vivo. We demonstrated that recombinant MIF (rMIF) treatment was able to reduce caspase-3 activation when cultures were challenged with the apoptosis-inducer Carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) while, in the cultures exposed to H/R, the treatment with rMIF did not show any effect. However, a significant increase in caspase-3 and caspase-8 activation was found when H/R-exposed cultures, were treated with anti-MIF or anti-CD74 antibody. We also observed that under H/R, a significant amount of endogenous MIF was released into the medium, which could account for the lack of effect of rMIF added to the cultures. Our results demonstrate for the first time that the MIF/CD74 axis contributes to maintain trophoblast homeostasis, by preventing abnormal apoptotic death.
Highlights
The placenta, the organ interposed between the mother and the foetus, performs critical functions for embryo growth i.e. the supply of nutrients, the transport of gases, ions, water and waste products[1]
In view of the above evidence, we suggest that Migration Inhibitory factor (MIF) exerts its action in the placenta and, in particular, we hypothesize that MIF protects trophoblast from apoptosis, a crucial cellular event in the earlier stages of pregnancy that could become harmful if not properly regulated[20]
In order to verify the sensitivity of placenta to MIF action we evaluated the CD74 expression in placental tissues throughout the first trimester of pregnancy
Summary
Received: 14 February 2018 Accepted: 10 July 2018 Published: xx xx xxxx placenta under induced stress conditions. By using the in vitro model of placental explants from first trimester pregnancy, we investigated the role of MIF in the survival of placental cells under induced stress conditions that promote apoptosis or mimic the hypoxia/re-oxygenation (H/R) injury that placenta could suffer in vivo. Various studies in different cell types, show that the pro-survival role of MIF is achieved through several distinct mechanisms, such as metabolic activation, autophagy induction, apoptosis suppression and anti-oxidative responses[9,10,11,12]. We investigated the role of exogenous and endogenous MIF and that of its receptor the CD74 in human placental explants at first trimester pregnancy, subjected to pro-apoptotic stimuli
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