Intrauterine infection/inflammation (IUI) is a frequent complication of pregnancy leading to preterm labor and fetal infllammation. How inflammation is modulated at the maternal-fetal interface is unresolved. We compared transcriptomics of amnion (a fetal tissue in contact with amniotic fluid) in a preterm rhesus macaque model of IUI-induced by lypopolysaccharide with human cohorts of chorioamnionitis. Bulk RNA-seq amnion transcriptomic profiles were remarkably similar in both rhesus and human subjects and revealed that induction of key labor-mediating genes such as IL1 and IL6 was dependent on NF-kB signaling and reversed by the anti-TNF antibody Adalimumab. Inhibition of collagen biosynthesis by IUI was partially restored by Adalimumab. Interestingly, single-cell transcriptomics, flow cytometry, and immuno-histology demonstrated that a subset of amnion mesenchymal cells (AMCs) increase CD14 and other myeloid cell markers during IUI both in the human and Rhesus macaque. Our data suggest that CD14+ AMCs represent activated AMCs at the maternal-fetal interface.
Presicce, P., Cappelletti, M., Morselli, M., Ma, F., Senthamaraikannan, P., Protti, G., et al. (2023). Amnion responses to intrauterine inflammation and effects of inhibition of TNF-signaling in preterm Rhesus macaque. ISCIENCE, 26(11 (17 November 2023)) [10.1016/j.isci.2023.108118].
Amnion responses to intrauterine inflammation and effects of inhibition of TNF-signaling in preterm Rhesus macaque
Protti, Giulia;
2023
Abstract
Intrauterine infection/inflammation (IUI) is a frequent complication of pregnancy leading to preterm labor and fetal infllammation. How inflammation is modulated at the maternal-fetal interface is unresolved. We compared transcriptomics of amnion (a fetal tissue in contact with amniotic fluid) in a preterm rhesus macaque model of IUI-induced by lypopolysaccharide with human cohorts of chorioamnionitis. Bulk RNA-seq amnion transcriptomic profiles were remarkably similar in both rhesus and human subjects and revealed that induction of key labor-mediating genes such as IL1 and IL6 was dependent on NF-kB signaling and reversed by the anti-TNF antibody Adalimumab. Inhibition of collagen biosynthesis by IUI was partially restored by Adalimumab. Interestingly, single-cell transcriptomics, flow cytometry, and immuno-histology demonstrated that a subset of amnion mesenchymal cells (AMCs) increase CD14 and other myeloid cell markers during IUI both in the human and Rhesus macaque. Our data suggest that CD14+ AMCs represent activated AMCs at the maternal-fetal interface.
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