Presence of Activated Macrophages in a Murine Model of Early Embryo Loss

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Abstract
PROBLEM: Even though our knowledge of the phenomenon at play at the fetoplacental interface has greatly advanced during the past years, a complete understanding of the reasons why the developing embryo is not rejected by maternal immune effector cells remains largely unknown. METHODS: We have used immunohistochemistry with the macrophage-specific markers F4/80 and MHC II to study the relationship between decidual infiltration and resorption in murine models of embryo loss between days 6 and 10 of gestation. RESULTS: Analysis of day 8 CBA/J × DBA/2 pregnancies has revealed 2 distinct populations of embryos. The majority (69.4%) expressed low levels of F4/80+ cells, but a minority (30.6%) expressed much higher level of the macrophage marker. In CBA/J × BALB/c, most embryos (91.7%) expressed low numbers of F4/80+ cells. As earlier experiments established that products of activated macrophages (TNF-α and nitric oxide) were implicated in embryo loss in this model, the activation status of the F4/80+ macrophages was assessed through the cell surface expression of MHC II. Again, a similar association was established: 30.6% of the CBA/J × DBA/2 embryos were infiltrated by significantly more MHC II+ cells than the control CBA/J × BALB/c mating. Finally, when coordinate expression of F4/80, MHC II and CD11b was assessed, it was found that an embryo significantly infiltrated by cells bearing one of the 3 markers was also heavily infiltrated by cells bearing the 2 other markers. CONCLUSIONS: This study has shown that the augmented infiltration of the deciduum with maternal macrophages is an early event which precedes spontaneous abortion of the early embryo.