Fetal and Maternal Transforming Growth Factor-(beta)1 May Combine to Maintain Pregnancy in Mice

One of the mysteries of pregnancy is why a mother does not reject her fetuses. Cytokine-modulation of maternal-fetal interactions is likely to be important. However, mice deficient in transforming growth factor-(beta)1 (TGF(beta)1) and other cytokines are able to breed, bringing this hypothesis into question. The phenotype of TGF(beta)1 null-mutant mice varies with genetic background. We report here that, in outbred mice, the loss of TGF(beta)1- deficient embryos is influenced by the parity of their mother. This is consistent with the loss of mutants being due to immune rejection. An inbred line of TGF(beta)1+/– mice that supported TGF(beta)1-deficient fetuses had high levels of TGF(beta)1 in their plasma. Analysis of the amniotic fluids in this line indicated that biologically relevant levels of maternal TGF(beta)1 were present in the TGF(beta)1–/– fetuses. These data are consistent with maternal and fetal TGF(beta)1 interacting to maintain pregnancy, within immune-competent mothers.