Fetal and maternal transforming growth factor-β1 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-beta1 (TGFbeta1) and other cytokines are able to breed, bringing this hypothesis into question. The phenotype of TGFbeta1 null-mutant mice varies with genetic background. We report here that, in outbred mice, the loss of TGFbeta1 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 TGFbeta1(+/-) mice that supported TGFbeta1-deficient fetuses had high levels of TGFbeta1 in their plasma. Analysis of the amniotic fluids in this line indicated that biologically relevant levels of maternal TGFbeta1 were present in the TGFbeta1(-/-) fetuses. These data are consistent with maternal and fetal TGFbeta1 interacting to maintain pregnancy, within immune-competent mothers.