Problem Increased embryonic resistance to teratogenic stresses as a result of maternal immunopotentiation is associated with a decrease in the intensity of teratogen-induced apoptosis in target embryonic structures. These findings suggest that this effect of maternal immunopotentiation might be realized through modification of the expression of molecules regulating the teratogen-induced apoptotic process. To examine this possibility, we evaluated caspases 3, 8 and 9 activation as well as nuclear factor (NF)-κB DNA-binding activity in the embryos of immunopotentiated mice exposed to cyclophosphamide (CP).
Methods of study The rate of resorptions and the proportion of malformed fetuses in CP-treated mice were recorded on day 19 of pregnancy. Activity of caspases was tested in cytoplasmic extracts collected from the embryonic brain 24 hr after CP treatment using appropriate fluorometric kits, whereas NF-κB DNA-binding activity was evaluated in nuclear extracts using the electrophoretic mobility shift assay.
Results As in our previous studies, immunopotentiated CP-treated females exhibited a lower rate of resorptions or fetuses with open eyes than their non-immunopotentiated counterparts. In parallel, we observed that maternal immunopotentiation normalized the CP-induced activation of the tested caspases as well as the CP-induced suppression of NF-κB DNA-binding activity.
Conclusions As caspases act as inducers of apoptosis, and NF-κB acts in CP-treated embryos as an apoptosis suppressor, the above results suggest that maternal immunopotentiation might affect embryonic sensitivity to embryopathic stresses via NF-κB- and caspases-associated pathways.