This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.To identify the function of MHC class I expression at the maternal-fetal interface.The rhesus monkey placenta expresses the nonclassical MHC class I molecule, Mamu-AG, which has HLA-G-like characteristics.
The aim of this study was to determine how anti-Mamu-AG passive immunization affects placental growth and development in the nonhuman primate. We conducted histological, morphometric and immunohistochemical (cytokeratin, SMA, Von Willebrand factor, VEGF, Flk-1, Ki-67 expression) analysis of placentas on day 24 of gestation of 12 rhesus monkeys (Macaca mulatta) with normal pregnancy (Untreated control), treated with non-specific antibodies or anti-Mamu-AG (clone 25D3) mAb from day 18 through day 24 of gestation. On day 24 in 25D3-treated placentas vs Untreated and Non-specific treated groups we found a delay in the histological features of implantation (degeneration of epithelial plaque, decline of edema, decidualization, lacunae organization). Small arteries directly beneath the implantation site were completely occluded by extravillous cytotrophoblasts in all animals, and while the arterial endothelial layer in all groups and the vascular smooth muscle tunica in Untreated and Non-specific treated groups was breached, in 25D3-treated animals the smooh muscle media remained intact. The length of stem villi and diameter of all villi were significantly less in 25D3-treated placentas. The proliferative index dramatically decreased in anti-Mamu-AG passive immunized monkeys compared to Untreated and Non-specific-treated groups. The number of vessels per villi, and diameter of villous vessels were less in 25D3-treated placentas. We propose that the anti-Mamu-AG-passive immunization in early gestation down-regulates trophoblastic modification of decidual vessels, placental vascularization, growth and development. This data suggest an important interaction between placental MHC class I expression and an appropriate enviroment for placental and vascular development in primate pregnancy. This research used WNPRC Animal Services and Research Services.
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