Immunoteratology: I. MHC Involvement in the Embryo Response to Teratogens in Mice

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Abstract
PROBLEM: The present study was carried out to evaluate an involvement of MHC-associated maternal immunoreactivity in response to environmental teratogens. METHODS: Two chemicals, cyclophosphamide (CP) and 2,3-quinoxalinedimetanol, 1,4-dioxide (QD) were used as the reference teratogens (RT). The response to these RT was investigated in syngeneically and allogeneically mated CBA/J and C57B1/6 mice. In part of C57B1/6 female mice, paraaortic lymph nodes were extirpated 14 days before mating to allogeneic or syngeneic males. Twenty or 40 mg/kg of CP or 300 or 600 mg/kg of QD were injected on day 12 and 9 of pregnancy, accordingly (vaginal plug indicates day 1 of pregnancy). On day 19 of pregnancy implantation sites, resorptions, live and dead fetuses were recorded and live fetuses were examined with methods routinely used in applied teratology. RESULTS: Both mice strains showed equal response to teratogens but the RT-induced effect was significantly weaker in allogeneic than syngeneic mouse combinations. Extirpation of draining lymph nodes dramatically increased the sensitivity to RT in allogeneically mated females but failed to alter that of syngeneically mated ones. CONCLUSION: The results of this study suggest that fetomaternal MHC incompatibility exerts the favourable influence on teratological resistance of the embryo and MHC-associated immunoreactivity of “mother-fetus” axis is possibly responsible for this effect.