Spatiotemporal patterns of macrophage migration inhibitory factor (Mif) expression in the mouse placenta.
BACKGROUND
Macrophage migration inhibitory factor (MIF) has special pro-inflammatory roles, affecting the functions of macrophages and lymphocytes and counter-regulating the effects of glucocorticoids on the immune response. The conspicuous expression of MIF during human implantation and early embryonic development also suggests this factor acts in reproductive functions. The overall goal of this study was to evaluate Mif expression by trophoblast and embryo placental cells during mouse pregnancy.


METHODS
Mif was immunolocalized at implantation sites on gestation days (gd) 7.5, 10.5, 13.5 and 17.5. Ectoplacental cones and fetal placentas dissected from the maternal tissues were used for Western blotting and qRT-PCR assays on the same gestation days.


RESULTS
During the post-implantation period (gd7.5), trophoblast giant cells showed strong Mif reactivity. In later placentation phases (gds 10.5-17.5), Mif appeared to be concentrated in the junctional zone and trophoblast giant cells. Mif protein expression increased significantly from gd7.5 to 10.5 (p = 0.005) and from gd7.5 to 13.5 (p = 0.03), remaining at high concentration as gestation proceeded. Higher mRNA expression was found on gd10.5 and was significantly different from gd13.5 (p = 0.048) and 17.5 (p = 0.009).


CONCLUSIONS
The up-regulation of Mif on gd10.5 coincides with the stage in which the placenta assumes its three-layered organization (giant cells, spongiotrophoblast and labyrinth zones), fetal blood circulation begins and population of uNK cells reaches high proportions at the maternal counter part of the placenta, suggesting that Mif may play a role in either the placentation or in the adaptation of the differentiated placenta to the uterus or still in gestational immunomodulatory responses. Moreover, it reinforces the possibility of specific activities for Mif at the maternal fetal interface.
Faria
Miriam R
MR
Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Hoshida
Mara S
MS
Ferro
Eloisa Av
EA
Ietta
Francesca
F
Paulesu
Luana
L
Bevilacqua
Estela
E
D000818:Animals; D010064:Embryo Implantation / Q000235:genetics / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation; D005865:Gestational Age; D007150:Immunohistochemistry; D019746:Intramolecular Oxidoreductases / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D010920:Placenta / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D014018:Tissue Distribution
D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse