Pregnancy and perforin: What could be the role of a ‘natural killer’ in the decidua?

Summary Perforin is a cytotoxic molecule which is found in high concentration at the fetomaternal interface. In this location, perforin is contained in a specialized subset of natural killer cells, called uterine NK cells. By the use of perforin-deficient mice, we studied the function of perforin in the pregnant uterus. Perforin-deficient mice, we studied the function of perforin in the pregnant uterus. Perforin-deficient mice were found to reproduce as efficiently as wild type controls; however, they differed from normal in that the frequency of uterine NK cells was significantly higher and these cells were found to proliferate during more advanced stages of pregnancy. Lipopolysaccharide, which caused a massive increase of fetal resorptions in C57BL/6 control mice when given intraperitoneally on day 6.5 of pregnancy, had the same effect in the perforin-deficient counterpart. This argues against uterine NK cells being effector cells in infection-mediated abortion. Furthermore, no differences in fertility were observed under restricted mating conditions and with severe social stress. However, when embryo transfer was performed, the implantation of blastocysts was achieved in unprepared endometrium of perforin-deficient mice, which was not possible in wild type controls of the same genetic background. This could argue for a role of perforin in the defense of the mother against undue pregnancies.