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Summary.
Mice of the CBA strain which had given birth to five litters sired by males of a different H-2 type (C57BL/10) showed evidence of immunization to paternal antigens, in that the numbers of lymphocytes forming alloclusters with paternal erythrocytes were significantly elevated. On the other hand, the graft-versus-host responsiveness of maternal splenic lymphocytes to paternal antigens remained virtually unchanged, showing only a slight increase at Day 8 of the assay.
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Summary. Lipid extraction was used to study the natural killer (NK) suppressive activity of individual feto-placental units. Normal pregnancies showed a lipophilic NK cell suppressive factor that was gestational day specific. Feto-placental units from CBA/J × DBA/2 pregnancies were deficient in the NK cell suppressive factor when compared to normal CBA/J × BALB/c pregnancies. The frequency of non-suppressive feto-placental units from CBA/J × DBA/2 pregnancies correlated with the frequency of feto-placental units infiltrated with NK cells and the frequency of spontaneous resorption. Our results implicate a deficiency of NK suppressive activity in the feto-placental unit as a contributing factor in spontaneous fetal resorption.
Keywords: pregnancy; resorption; natural killer cells; immunosuppression; mouse
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Pregnancy outcome may be altered by both genetic and environmental factors. The mating of CBA/J female mice with DBA/2 males normally results in pregnancies characterized by a relatively high incidence of early embryo loss compared with most other syngeneic or allogeneic matings. This study addressed the role of normal laboratory stress in the induction of early embryo loss. The previously studied 'Bruce effect' describes the total loss of preimplantation embryos (pregnancy block) that is apparently caused by the stress induced by the presence of an alien male and mediated by neuroimmunological effects on prolactin activity. To determine whether this effect could be responsible for the high incidence of postimplantation embryo losses in the CBA/J × DBA/2 model, the original DBA/2 male was replaced on day 6 of gestation by another DBA/2 male, a CBA/J, a C57Bl/6 or a BALB/c male. The relatively high incidence of embryo loss was not affected by removing the original DBA/2 male or introducing another DBA/2 or a CBA/J male, indicating that stress induced by an alien male did not increase the postimplantation losses in this model. Furthermore, the introduction of a DBA/2 male to a CBA/J female that had been mated with a BALB/c male did not elicit early embryo loss. However, the replacement of the original DBA/2 male by a BALB/c male dramatically reduced the incidence of early embryo loss in pregnant CBA/J female mice. The introduction of a C57Bl/6 male also reduced embryo loss but to a lesser extent. Furthermore, this effect was shown to be independent of the testes and was induced by factors present in the bedding from cages in which BALB/c male mice had been housed. The presence of the BALB/c male in the cage with the pregnant CBA/J female resulted in a significant reduction in the infiltration of uterine implantation sites by maternal macrophages, coincident with a reduction in early embryo losses. These studies therefore show that the maternal cell-mediated immune response in the uterus to the fetal graft is altered, apparently by pheromonal messages derived from the resident male. The introduction of an alien BALB/c male to a pregnant CBA/J female after implantation of CBA/J × DBA/2 embryos had occurred, while unable to alter the fetal genotype, apparently altered the maternal uterine cellular response and had a profound effect on pregnancy outcome.
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Summary. Certain strains of mice display an increased frequency of fetal resorption, but little is known about the effector mechanisms involved. We have examined the events associated with lipopolysaccharide (LPS)-induced fetal resorption in mice. Administration of 25 μg LPS on Day 12 of gestation resulted in the appearance of tumour necrosis factor-alpha (TNF-α) in the amniotic fluid and fetal resorption. Levels of LPS-induced TNF-α were reduced by 90% after pretreatment with the TNF-α-suppressing drug pentoxifylline (PXF). Treatment of pregnant mice during early gestation with 0·1 μg LPS resulted in fetoplacental resorption which was maximal when the LPS was given on Day 8. Resorption induced by 0·1 μg LPS on Day 8 of gestation was significantly reduced by pretreatment with PXF. Infiltration of asialo-GM1-positive cells was observed in the decidual–ectoplacental cone area of embryonic units from LPS-treated mice. In addition, treatment with anti-AGM1 antiserum prevented the LPS-induced resorption. Our results suggest that TNF-α and asialo-GM1-positive cells are involved in LPS-induced fetal resorption.
Keywords: abortion; lipopolysaccharide; TNF-α; natural killer cells; pentoxifylline; mouse
