THE ROLE OF PERFORIN-EXPRESSION BY GRANULAR METRIAL GLAND-CELLS IN PREGNANCY

The pregnant uterus of humans and rodents contains a population of gra nulated lymphoid cells, which, in the mouse, are called granular metri al gland (GMG) cells and have been described to express high levels of perforin. Since there is evidence for cytolytic activity of these cel ls and since perforin is a crucial effector molecule for the lytic act ion of cytotoxic T cells and natural killer cells, we evaluated the fu nction of perforin in the pregnant uterus by using perforin-deficient mice. Perforin-deficient female mice were found to reproduce as effici ently as normal control females when bred either with syngeneic or all ogeneic males. However, perforin-deficient mice differed from normal m ice in that the frequency of GMG cells was significantly higher within maternal blood spaces and within several compartments of the fete-mat ernal interface. Proliferating GMG cells, identified by [H-3]thymidine incorporation, were observed during more advanced stages of pregnancy when compared to normal controls. In contrast to normal mice, perfori n-deficient mice did not display GMG cells attached to degenerating tr ophoblasts; instead perforin-deficient GMG cells were often observed i n association with small maternal lymphocytes. In addition, the lack o f transmission of lymphocytic choriomeningitis virus from infected pre gnant perforin-deficient mice to the fetuses argued against a role of perforin expression by GMG cells in prevention of virus transmission f rom the mother to the fetus. Our data indicate that functional perfori n is not necessary for successful pregnancies. The morphological chang es in the pregnant uterus of perforin-deficient mice might, however, p oint to a certain, as-yet undefined function of perforin in the uterus of pregnant normal mice, which is functionally compensated in perfori n-deficient mice.