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Spontaneous abortion in immunodeficient SCID mice
D A Clark1, C Quarrington, D Banwatt
1Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Summary
SCID mice on the CB-17 background exhibit high spontaneous resorption rates, suggesting a TNF-alpha-induced vasculopathy, not immunodeficiency, is responsible. Genetic background and embryo genotype significantly influence abortion susceptibility.
Area of Science:
- Reproductive immunology
- Mouse models of pregnancy loss
- Genetics of reproduction
Background:
- Recurrent miscarriage research often uses xenogeneic blastocyst transfer models.
- Interpretation requires understanding syngeneic mating success rates in immunodeficient mice.
- Immunotrophic factors are typically expected in immunocompetent, non-T-cell deficient mice.
Purpose of the Study:
- To investigate the role of "rejection" in a xenogeneic blastocyst transfer model of recurrent miscarriage using immunodeficient SCID mice.
- To determine if syngeneic matings in SCID mice have high success rates.
- To identify factors influencing resorption rates in different mouse genetic backgrounds.
Main Methods:
- Studied resorption rates in SCID CB-17 mice within a barrier facility.
- Administered anti-asialo GM1 antibody and GM-CSF to assess their effects on resorption.
- Conducted mating experiments to evaluate embryo genotype influence on loss.
- Analyzed decidual tissue for inflammatory markers (TNF-alpha, TGF-beta).
- Assessed the impact of genetic background (C57B1/6 outcrossing) and microbial flora.
Main Results:
- SCID CB-17 mice showed unexpectedly high spontaneous resorption rates.
- Immunocompetent CB-17 mice exhibited even higher loss rates.
- Treatments effective in other models (anti-asialo GM1, GM-CSF, tetracycline, progesterone) were ineffective.
- Presence of +/+ embryos augmented abortion, particularly against scid/scid embryos.
- High abortion rates correlated with Staphylococcus sp. in feces and altered SPF flora.
- Decidual tissue revealed premature TNF-alpha release and vascular lesions (fibrinoid necrosis).
- Outcrossing onto C57B1/6 background significantly reduced abortion rates, indicating genetic protection.
Conclusions:
- SCID CB-17 mice do not achieve high syngeneic pregnancy success; TNF-alpha-induced vasculopathy is implicated.
- Abortion is not due to immunodeficiency-related loss of immunotrophism.
- Augmenting factors include +/+ embryo genotype and anti-asialo GM1 treatment.
- Genetic background and heterozygosity/SCID mutation offer protection against abortion.
- An infectious trigger for vasculopathy and significant genetic influence on susceptibility are suggested.