Fetal surgery is a promising strategy to treat fetuses with severe congenital abnormalities but its clinical applications are often limited by preterm labor. In normal pregnancy, multiple mechanisms protect the semi-allogeneic fetus from attack by maternal T cells. Maternal microchimerism (the presence of maternal cells in the fetus) has been suggested to be one mechanism of maternal-fetal tolerance in that it exposes the fetus to non-inherited maternal antigens and leads to the generation of fetal regulatory T cells that can suppress a maternal T cell response. Preterm labor may represent a breakdown of this robust tolerance network. We hypothesized that during inflammation-associated preterm labor, maternal leukocytes cross the maternal-fetal interface and enter the fetal circulation. Consistent with this hypothesis, we found that during preterm labor in mice, the percentage of maternal microchimerism in fetal blood increased and the frequency of fetuses with high levels of trafficking (greater than 0.5%) also increased. Finally, we showed that the maternal leukocytes trafficking into the fetus are primarily Gr-1(+) cells in both syngeneic and allogeneic pregnancy, while T cell trafficking into the fetus specifically increases during allogeneic pregnancies. Our results demonstrate that trafficking of maternal leukocytes during pregnancy is altered during preterm labor. Such alterations may be clinically significant in affecting maternal-fetal tolerance.
Keywords: LPS-induced preterm labor; maternal microchimerism; maternal-fetal cellular trafficking; preterm labor.