Perforin improves the morphogenesis of mouse placenta disturbed by IL-2 treatment

The pore-forming protein (perforin) produced by lymphocytes can induce apoptosis in target cells. In mouse placenta, although a large amount of perforin is produced by the uterine natural killer (uNK) cells, its role in the reproductive process is still not clear. Since the cytotoxicity of uNK cells can be enhanced by interleukin (IL)-2, we studied the role of perforin in the placenta of wild-type and perforin-knockout mice treated with IL-2 during days 10-14 of pregnancy. Immunohistochemistry of the wild-type mice showed that the perforin was positive in the membrane of trophoblast glycogen cells as well as the cytoplasm of uNK cells, and there was an increase in the expression level following IL-2 treatment as revealed by RT-PCR analysis, although no change was identified in fertility. In the IL-2-treated perforin-knockout mice, however, the number of live fetuses was decreased, accompanied by an increase in the weight of placentae. Examination of these placentae showed an abnormally enlarged junctional zone, occupied by a large number of the trophoblast glycogen cells and significantly few of the apoptotic cells. These findings indicate that perforin can contribute to a successful pregnancy by inhibiting the excessive growth of the junctional zone induced by IL-2.