Peri-implantation mouse embryos: an in vitro assay for assessing serum-associated embryotoxicity in women with reproductive disorders.
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Abortion, Habitual↗
Biomedical subjects
V Toder
Publications and source records attributed to V Toder.
Immune reproductive failure: effect of nonspecific immunostimulation in mouse model.
There is much evidence that pregnancy loss may be immunologically mediated. Failure of the maternal immune system to actively support the pregnancy may be responsible for its demise. Potentiation of immune functions has been attempted in humans; however, the success of immunotherapy is still not clear. Thus immunotherapy experiments in mouse models are important. Nonspecific immuno-stimulation with complete Freund adjuvant (CFA) was shown in our laboratory to reverse the tendency to fetal loss in the CBA/J X DBA/2J mouse combination. CFA elevates the non-T lymphocyte population, decreases T-cell secreted lymphokines, and enhances macrophage-secreted monokines. However, a relationship between these changes and a beneficial effect of CFA on reproductive performance has to be proved. Information obtained from nonspecific immunopotentiation in the CBA/J-DBA/2J model may contribute the assessment of nonspecific immunotherapy in humans.
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Immune features in complete Freund adjuvant-treated CBA/J mouse model.
Immunostimulation with complete Freund adjuvant (CFA) reverses the tendency to fetal loss in the CBA/J x DBA/2J mouse. First attempts to understand the mechanisms underlying this effect were to evaluate phenotypic and functional changes in the lymphocytic cell population after immunopotentiation. We demonstrated that treatment with CFA leads to diminished responses of maternal splenocytes towards paternal alloantigens and this low response cannot be improved with exogenous interleukin-2. Lymphocytes derived from spleen, para-aortic draining lymph nodes and placenta significantly suppress maternal response to paternal antigens. The effect of low fetal resorption rate is followed by marked elevation of asialo GM-1 and HNK-1-positive cells but not followed by any change of the L3T4 or Lyt-2-positive lymphocyte population in either the spleen or in draining lymph nodes. L3T4 and Lyt-2-positive cells have not been found in the placenta. An important feature was marked elevation of Mac-1-positive cells in the placentas of CFA-treated animals. The relevance of these findings to CFA-induced fetal protection is still under investigation.
Animals↗
Immunotherapy of habitual abortion.
Many cases of habitual abortion have been assumed to be due to hyporesponsiveness to the spouse's antigens encountered in pregnancy. Immunization by paternal leukocytes has been used to potentiate the immune response and prevent further miscarriages. This treatment has been highly controversial in terms of efficacy, mode of action, and side effects. More recently immunoglobulin has been used as passive immunization for similar indications. In our experience immunotherapy is effective; 80% of patients have subsequent live births. The most significant results are seen in patients with five or more abortions, in whom 66% of subsequent pregnancies develop normally compared to 20% in a control group. We have used antipaternal complement-dependent antibody (APCA) production after immunization as a marker of immune response. APCA correlates with beneficial outcome in the next pregnancy. APCA may also be associated with cytokines, which may enhance embryonic and trophoblast development. Immunoglobulin may similarly provide the relevant antibodies or cytokines. At present a large scale meta-analysis is being performed to confirm or refute the efficacy of this treatment. This meta-analysis may resolve the controversy.
Abortion, Habitual↗
Effect of paternal leukocyte immunization on implantation after biochemical pregnancies and repeated failure of embryo transfer.
PROBLEM: It is unclear how paternal leukocyte immunization prevents pregnancy loss. We investigated whether immunization affects early pregnancy, and whether it increases the rate of implantation and early embryonic development at the time of implantation. METHOD: Three groups of women with possible implantation failure were immunized: (1) recurrent biochemical pregnancies (> 3), (2) three or more failed in vitro fertilization (IVF) cycles, and (3) IVF after immunization for recurrent abortion (> 3). Patients were immunized if antipaternal complement-dependent antibody (APCA) was negative, and mixed lymphocyte culture hyporeactive to husbands lymphocytes. Immunizations were prepared from 100 ml paternal blood separated by Ficoll Hypaque density centrifugation. IVF was attempted after APCA was produced. RESULTS: In the women with biochemical pregnancies, 10 to 12 subsequent pregnancies developed normally. Seventy-nine subsequent IVF cycles in 33 patients resulted in 20 pregnancies, 16 of which developed normally. Six pregnancies followed 30 cycles in recurrent failed IVF, and 14 pregnancies from 49 cycles in 23 patients with previous habitual abortion. CONCLUSIONS: This treatment may prevent further biochemical pregnancies if control studies confirm this preliminary observation, but was not shown to affect recurrent failed embryo transfer.
Abortion, Habitual↗
[The erythroblast antigen: a membrane protein bound to the erythroid form of the transferrin receptor?].
An interspecific marker of mammalian erythroid cells, which was called the erythroblast antigen, was identified in 1974, using polyclonal monospecific antibodies. Further studies have demonstrated the expression of this antigen in a variety of nonhemopoietic organs and tissues, which have the following common feature: they have a barrier location; that is, they are located at the boundary. It has been proposed that the erythroblast antigen participates directly or indirectly in the transport of various substances and specifically transport of iron. The present review deals with this topic.
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