Placental expression of the nonclassical MHC class I molecule Mamu-AG at implantation in the rhesus monkey

During human implantation trophoblasts mediate attachment of the embryo to the uterine epithelium and invade and reorganize vessels of the maternal endometrium to initiate blood flow to the intervillous space. Expression of the nonclassical MHC class I molecule HLA-G by invading trophoblasts may play a central role in their protection from recognition by the maternal immune system; however, the ontogeny of trophoblast HLA-G expression during the earliest stages of implantation is difficult to evaluate in human pregnancy. We previously identified a novel nonclassical MHC class I molecule, Mamu-AG, which is expressed in the rhesus monkey placenta and shares many unique characteristics of HLA-G. Immunocytochemical analysis with a Mamu-AG-specific mAb and locus-specific in situ hybridization of rhesus implantation sites 7-12 days after embryo attachment (days 14-19 of pregnancy) demonstrated that Mamu-AG molecules are expressed predominantly in cytotrophoblasts invading the maternal vessels and endometrium, whereas syncytiotrophoblasts covering trophoblastic lacunae or newly formed chorionic villi remained largely Mamu-AG-negative. By day 36 of pregnancy, Mamu-AG glycoprotein also was expressed in villous syncytiotrophoblasts, and accumulation of Mamu-AG glycoprotein was noted at the border between maternal decidua and fetal trophoblasts. The ontogeny of a nonclassical MHC class I molecule at the implantation site supports the hypothesis that its expression is important for the establishment of maternal-fetal immune tolerance.