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Keywords:

  • Abortion;
  • cytokines;
  • macrophage;
  • mouse;
  • pregnancy

PROBLEM: There is considerable controversy concerning the root cause and mechanisms of early embryo loss. It has been suggested that most pregnancy losses occur due to morphogenetic anomalies of the embryo. It has also been suggested that the maternal specific immune system rejects the embryo.

METHODS: Existing data on the cell and molecular biology of early embryo loss in murine experimental models is reviewed.

RESULTS: Using the CBA ♀ × DBA/2 ♂ model of early embryo loss, it has been established that maternal inflammatory cells infiltrate the decidua basalis of all implantation sites within 48 hr after implantation. For most embryos, the relatively low numbers of macrophages (MΦ) and natural killer-like (NK-like) cells of maternal origin remain relatively constant after day 8, whereas 20–30% of the embryos show a significant increase in inflammatory cells in the maternal decidua, corresponding to the incidence of early embryo resorption visible at day 12. Evidence will be reviewed to suggest that decidual NK-like cells are not cytolytic but may be producing the MΦ-activating cytokine interferon gamma (IFN-γ), which activates decidual MΦ and other cells. Furthermore, embryo loss is ameliorated by in vivo treatment with anti-IFNγ or anti-NK antisera, indicating that NK-like cells and/or IFNγ are required for embryo loss, but not for embryo survival. In resorbing embryos, the inflammatory MΦ show evidence of having been primed during early pregnancy, in that in vitro incubation with lipopolysaccharide induced the production of tumor necrosis factor alpha and nitric oxide.

CONCLUSION: These findings support the concept that early embryo loss is a nonspecific event mediated by the triggering of cytotoxin production by primed decidual macrophages.