Production of Embryotoxic IgG Antibodies During IFN‐γ Treatment of Pregnant Mice

PROBLEM: Administration of IFN‐γ during pregnancy in mice is deleterious not only to fetal survival but also to maternal physiology. Thus, injection of recombinant IFN‐γ from days 6–11 of gestation results in significant increase of fetal abortion, decrease of fetal weight accompanied by morphological defects of the embryo, and induction of class II MHC antigens on the spongiotrophoblast zone of the placenta. At the maternal level, this treatment causes splenomegaly, decrease of hematocrit levels, and increase of IgG production. In an attempt to dissect out the different phenomena observed, we examined the properties of polyclonal IgG antibodies contained in the animals' serum as to their ability to recognize antigenic determinants on IFN‐γ‐induced placentae and isolated trophoblasts. METHOD: Serum from IFN‐γ‐treated pregnant mice was tested in vitro for its ability to recognize specific structures on primary trophoblasts and placental sections induced by IFN‐γ. In vivo this serum was injected in pregnant mice, and the outcome of pregnancy was evaluated. Monoclonal antibodies, resulting from the fusion of spleen cells from IFN‐γ‐treated pregnant mice to a myeloma cell line, were used to certify the IgG‐dependent embryotoxic effects observed with the polyclonal serum. RESULTS: It was demonstrated that both the polyclonal serum and the monoclonal antibodies recognize antigenic determinants only on the IFN‐γ‐induced trophoblasts, placentae, and embryos, reduce fetal size, and cause splenomegaly in the mother, but do not affect the percentage of abortions as compared to controls. CONCLUSIONS: IFN‐γ induces specific protein(s) on trophoblasts, which are responsible for embryotoxic antibody production in the mother. Since human abortion has been correlated with the production of embryotoxic IgG antibodies, this animal model may prove to be a useful tool in the analysis of events leading to pregnancy loss.