Early embryo loss is associated with the prior expression of macrophage activation markers in the decidua.
In early embryo loss, the activation of maternal immune effector mechanisms play a critical role in determining the success or failure of a pregnancy. We have previously shown that increased nitric oxide production by decidual macrophages is involved in early embryo loss occurring at day 12 of gestation. In this study, using reverse transcription-PCR and Southern blotting, the expression of inducible nitric oxide synthases (iNOS) and TNF-alpha mRNA was determined to quantify macrophage activation in individual murine embryos in a model of spontaneous early embryo loss. At day 8 of gestation, 32 and 29% of embryos with no apparent pathology showed an increase in iNOS and TNF-alpha mRNA expression, respectively. This corresponds to the natural resorption rate seen in the mouse model. In addition, the percentage of embryos with increased iNOS and TNF-alpha mRNA expression was further augmented when pregnant mice were induced to abort at a higher rate. These results showed, for the first time, a correlation between increased iNOS and TNF-alpha expression and embryo resorption. The results provide evidence for the presence of activated macrophages at implantation sites before overt embryo damage occurs.
Haddad
E K
EK
Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
Duclos
A J
AJ
Lapp
W S
WS
Baines
M G
MG
D000818:Animals; D003656:Decidua / Q000276:immunology*; D020964:Embryo Loss / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase