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Variation in Macrophage-Migration-Inhibitory-Factor Immunoreactivity During Porcine Gestation¹

Department of Physiology,³ University of Siena, 53100 Siena, Italy Department of Basic Animal and Veterinary Sciences,⁴ The Royal Veterinary and Agricultural University, DK-1870 Frederiksberg C, Denmark

The localization and activity of macrophage migration inhibitory factor (MIF) was investigated in the interhemal region of the noninvasive, diffuse, folded epitheliochorial placenta and in the nonpregnant uterus of the pig. MIF, a proinflammatory cytokine with many actions on macrophages and monocytes, may play an important role in materno-fetal immuno-tolerance during placental establishment, modulation, and growth. Immunohistochemical staining with anti-human MIF polyclonal antibodies was carried out on placental sections from 11 stages of gestation (16–95 days postcoitus) and on nonpregnant uterus at 13 days postestrus. Western blot analysis confirmed the specificity of the anti-human MIF polyclonal antibodies on pig tissues. MIF staining was intense in both the trophoblast and maternal epithelium in the early stages; in the later stages, it decreased dramatically in the maternal epithelium but remained high in the trophoblast. The uterine glands showed immunoreactivity at all stages, and the maternal and fetal epithelial linings of the areolar cavity showed high reactivity at Day 25. The vasculature also showed staining for MIF, and an intense to moderate staining was shown in the nonpregnant uterus, mostly in the surface and glandular epithelium. The high activity of MIF in the maternal and fetal tissues throughout placentation and its expression in the nonpregnant uterus indicate a regulatory role for MIF during embryo receptivity and epitheliochorial placentation.

¹ Supported by a grant from the Danish Veterinary and Agricultural Research Council and by research grant PAR 2003 from University of Siena.

² Correspondence: Vibeke Dantzer, Department of Basic Animal and Veterinary Sciences, The Royal Veterinary and Agricultural University, Gronnegaardsvej 7, DK-1870 Frederiksberg C, Denmark. FAX: 45 35 28 25 47; vd{at}kvl.dk

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