EARLY EMBRYO LOSS IS ASSOCIATED WITH THE PRIOR EXPRESSION OF MACROPHAGE ACTIVATION MARKERS IN THE DECIDUAL

In early embryo loss, the activation of maternal immune effector mecha nisms play a critical role in determining the success or failure of a pregnancy. We have previously shown that increased nitric oxide produc tion by decidual macrophages is involved in early embryo loss occurrin g at day 12 of gestation. In this study, using reverse transcription-P CR and Southern blotting, the expression of inducible nitric oxide syn thases (iNOS) and TNF-alpha mRNA was determined to quantify macrophage activation in individual murine embryos in a model of spontaneous ear ly embryo loss. At day 8 of gestation, 32 and 29% of embryos with no a pparent pathology showed an increase in iNOS and TNF-a mRNA expression , respectively. This corresponds to the natural resorption rate seen i n the mouse model. In addition, the percentage of embryos with increas ed iNOS and TNF-alpha mRNA expression was further augmented when pregn ant mice were induced to abort at a higher rate. These results showed, for the first time, a correlation between increased iNOS and TNF-alph a expression and embryo resorption. The results provide evidence for t he presence of activated macrophages at implantation sites before over t embryo damage occurs.