Fetal Tissues Reflect Decidual-Placental Inflammation

Abstract Maternal inflammation can negatively impact the development of the fetus, leading to long term adverse health outcomes. We previously reported that injection of Tisseel (surgical glue) into the maternal-fetal interface led to necrosis and inflammation skewing the peripheral fetal immunome into a pro-inflammatory state. Here, we extend those observations and report that decidual inflammation leads to similar outcomes in fetal organs. Tisseel or saline (n = 3) was injected directly into the placenta of pregnant (~GD90) rhesus macaques. C-sections were performed at ~GD150. Fetal tissues (lung, thymus, spleen, liver) were collected at necropsy, homogenates were prepared from all fetal tissues, and cytokine levels were measured by cytometric bead analysis. Mononuclear cell suspensions were prepared from thymus and spleen, labeled with antibodies against major immune cell lineages, and acquired using the Cytek Aurora. Data was analyzed using Specter (R), statistical significance was determined by Student’s t-test (p < 0.05). Tisseel group fetuses had higher levels of IL17A (lung, spleen), MCP1, and IL6 (liver). Interestingly, there was a trend towards elevated IL6 in the thymus of saline group fetuses. Additionally RORγt+ T cells were elevated in the thymus of Tisseel group fetuses, while T Regswere elevated in saline group. The spleen from Tisseel group fetuses had a higher proportion of T H1-like cells. Interestingly, T-bet+ B cells, linked to autoimmune disorders, were also elevated in the Tisseel group. Our preliminary results suggest that decidual/placental inflammation leads to a pro-inflammatory immunome in fetal organs. Further studies are needed to determine the functional properties of these altered immune populations.