Relationship between Decidual Leukocyte Infiltration and Spontaneous Abortion in a Murine Model of Early Fetal Resorption

Abstract

The relationship between the early cellular response to embryo implantation and subsequent embryo survival was explored. Immunohistochemistry using the anti-CDI 1b antibody (Mac-I) was used to localize and quantify maternal inflammatory cells present at the fetoplacental interface. CDI 1b is expressed mostly on macrophages, but is also present on natural killer (NK) cells, neutrophils, and B cells. The occurrence of CDI 1b-positive cells at the fetoplacental interface was quantified in CBA/J females mated by DBA/2 males (20-30% embryo loss) and CBA/J females mated by BALB/c males (5-10% embryo loss) in order to investigate the relationship between infiltration by these types of cells and subsequent embryo loss. CDI 1b-positive cells were found to infiltrate decidua of each embryo starting at Day 6 of gestation. Their numbers sharply increased on Days 7 and 8, to a plateau on Days 8 to 10, well before any damage to the embryo is macroscopically visible on Days 10 to 12 of gestation. The resorption-prone mating of CBA/J female by DBA/2 male showed a significantly elevated number of CDI 1b-positive cells in 26% of the embryos on the eighth day of gestation compared to CBA/J female by BALB/c male matings which were taken as the reference mating. Moreover, experimental conditions modulating fetal survival in CBA/J mothers such as poly (I:C) treatment of DBA/2-mated females (lower survival) or mating with BALB/c males (higher survival than with the mating with DBA/2 males), were found to be associated with high or low numbers of CDI 1b-positive cells at the fetoplacental interface. Furthermore, injection of anti-CDI 1b into pregnant mice at Day 6 of gestation significantly reduced the subsequent incidence of resorption in the resorption prone CBA/J x DBA/ 2 mating. These results suggest that CDI 1b-positive cells are associated with the etiology of spontaneous abortion in this system.