PRESENCE OF ACTIVATED MACROPHAGES IN A MURINE MODEL OF EARLY EMBRYO LOSS

PROBLEM: Even though our knowledge of the phenomenon at play at the fe toplacental interface has greatly advanced during the past years, a co mplete understanding of the reasons why the developing embryo is not r ejected by maternal immune effector cells remains largely unknown. MET HODS: We have used immunohistochemistry with the macrophage-specific m arkers F4/80 and MHC II to study the relationship between decidual inf iltration 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 pregna ncies has revealed 2 distinct populations of embryos. The majority (69 .4%) expressed low levels of F4/80(+) cells, but a minority (30.6%) ex pressed much higher level of the macrophage marker. In CBA/J x BALB/c, most embryos (91.7%) expressed low numbers of F4/80(+) cells. As earl ier experiments established that products of activated macrophages (TN F-alpha and nitric oxide) were implicated in embryo loss in this model , the activation status of the F4/80(+) macrophages was assessed throu gh 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 ma ting. Finally, when coordinate expression of F4/80, MHC II and CD11b w as assessed, it was found that an embryo significantly infiltrated by cells bearing one of the 3 markers was also heavily infiltrated by cel ls 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 emb ryo.