Presence of activated macrophages in a murine model of early embryo loss.

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 x 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 FBA/J x BALB/c, most embryos (91.7%) expressed low numbers of F4/80+ cells. As earlier experiments established that products of activated macrophages (TNF-alpha 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 x DBA/2 embryos were infiltrated by significantly more MHC II+ cells than the control CBA/J x 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.