A model of sterile placental inflammation: Tisseel-induced thrombotic lesions leads to increased expression of inflammation associated genes in the rhesus macaque placenta 2472

Abstract Description Thrombotic events at the placenta have been associated with pregnancy pathologies, such as preeclampsia (PE) and fetal growth restriction (FGR). Both PE and FGR are characterized by increased placental inflammation. Tisseel, a surgical glue, or saline was injected directly into the placenta of pregnant (∼GD90) rhesus macaques. C-sections were performed at ∼GD155. Two placental cotyledons – one with high levels of pathology (Tisseel High) and one with low levels of pathology (Tisseel Low) – from a Tisseel-treated placenta and one low-pathology cotyledon from a Saline placenta, were processed for spatial transcriptomics (CytAssist Visium Human Transcriptome probe kit). Data was analyzed using the Partek Flow Bioinformatics Suite. The top 10 differentially expressed (DE) genes across the three cotyledons show that the Tisseel High cotyledon had higher expression of inflammation-associated genes (ccxl8, ccl21), as well as natural killer cell associated genes (cd8a, nkg7, prf1). We found 63 DE genes between Tisseel Low and Saline cotyledons, suggesting that there is placental wide impact resulting from Tisseel treatment regardless of local, cotyledon-specific pathology. Localization of the top 3 DE inflammation-associated genes (krt14, ccl21, cxcl10) show higher levels of expression in the Tisseel High cotyledon, with the highest expression levels seen in the chorionic membrane. These data demonstrate that Tisseel-induced thrombosis leads to an increase in placental inflammation. Funding Sources Supported by NIH R01HD103443; NIH P51OD011106; NIH K01AI182448 Topic Categories Mucosal and Regional Immunology (MUC)