Abstract
Neuropilin-1 (NRP-1) is an essential regulator of maternal immune tolerance, placentation, and angiogenesis. Its dysregulation in preeclampsia (PE) and human immunodeficiency virus (HIV) infection implicates NRP-1 in disease susceptibility and progression. Therefore, this study investigates placental NRP-1 immunoexpression in HIV-complicated preeclamptic pregnancies in South African women of African ancestry receiving antiretroviral therapy. Immunohistochemistry of recombinant anti-neuropilin-1 antibody was performed on placental tissue from 30 normotensive and 60 early onset (EOPE) and late-onset (LOPE) preeclamptic women stratified by HIV status. Qualitative analysis of NRP-1 immunostaining within the chorionic villi revealed a predominant localization in trophoblasts and syncytial knots as well as endothelial, fibroblast-like, and Hofbauer cells. Following morphometric evaluation, we report that PE and HIV infection and/or antiretroviral usage independently downregulate placental NRP-1 immunoexpression; however, as a comorbidity, this decline is further augmented within the conducting and exchange villi. Furthermore, reduced immunoexpression of NRP-1 in EOPE compared with LOPE villi may be due to maternal-fetal maladaptation. It is plausible that the decreased NRP-1 immunoexpression in PE placentae facilitates syncytiotrophoblast apoptosis and subsequent deportation of NRP-1 into the maternal circulation, contributing to the anti-angiogenic milieu of PE. We hypothesize that the intense NRP-1 immunoreactivity observed in Hofbauer cells at the maternal-fetal interface may contribute to the natural prevention mechanism of HIV vertical transmission.