Decidual infiltration and activation of macrophages leads to early embryo loss.
OBJECTIVE
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(female) x DBA/2(male) 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 (Mphi) 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 Mphi-activating cytokine interferon gamma (IFN-gamma), which activates decidual Mphi and other cells. Furthermore, embryo loss is ameliorated by in vivo treatment with anti-IFNgamma or anti-NK antisera, indicating that NK-like cells and/or IFNgamma are required for embryo loss, but not for embryo survival. In resorbing embryos, the inflammatory Mphi 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.


CONCLUSIONS
These findings support the concept that early embryo loss is a nonspecific event mediated by the triggering of cytotoxin production by primed decidual macrophages.
Baines
M G
MG
Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
Duclos
A J
AJ
Antecka
E
E
Haddad
E K
EK
D000818:Animals; D003433:Crosses, Genetic; D003602:Cytotoxicity, Immunologic; D003656:Decidua / Q000473:pathology*; D005260:Female; D005327:Fetal Resorption / Q000209:etiology* / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics; D011247:Pregnancy; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase