Modulation of Embryo Sensitivity to Teratogen by Nonspecific Intrauterine Immunopotentiation

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Abstract
A recent study demonstrated that the sensitivity of mouse embryos to environmental teratogens may be dependent on fetomaternal immunoreactivity. The intrauterine stimulation of the female's immune response with MHC-specific paternal splenocytes was shown to enhance the tolerance of F1 embryos to cyclophosphamide (CP)-induced embryotoxic effect. The present study was undertaken to test whether MHC-nonrelated immunization could also influence embryo resistance to teratogens. Intrauterine (IU) or intraperitoneal (IP) inoculation of xenogeneic rat splenocytes (RS) to ICR mice was performed 3 weeks before mating and/or on day 1 of pregnancy. CP was injected on day 12 of pregnancy. Females were examined on day 19 of pregnancy with methods routinely used in segment II teratological studies. MHC-independent immunopotentiation with RS was demonstrated to enhance significantly the tolerance of ICR embryos to CP. Thus, the IU immunization performed 21 days before mating decreased the resorption rate in females treated with 40 mg/kg CP from 83% (nonimmunized females) to 54% (p <.05). In females treated with 15 mg/kg CP, such an immunization decreased the proportion of malformed fetuses from 82% (nonimmunized females) to 49% (p <.05). Furthermore, the protective effect of IU immunization performed twice (21 days before mating and on day 1 of pregnancy) was stronger than that of a single immunization. In parallel, it was observed that the IP immunization did not alter CP-induced embryotoxic effect. These results show that MHC-nonrelated maternal immunopotentiation influences the response to environmental teratogens. They also show that the IU route of the RS inoculation is preferable to modulate CP-induced teratogenesis.
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