Intrauterine infection/inflammation (IUI) is a frequent complication of pregnancy leading to preterm labor and fetal inflammation. 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 lipopolysaccharide with human cohorts of chorioamnionitis. Bulk RNA sequencing (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 nuclear factor KB (NF-kappa B) signaling and reversed by the anti-tumor necrosis factor (TNF) antibody Adalimumab. Inhibition of collagen biosynthesis by IUI was partially restored by Adalimumab. Interestingly, single-cell transcriptomics, flow cytometry, and immunohistology 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.
Amnion responses to intrauterine inflammation and effects of inhibition of TNF signaling in preterm Rhesus macaque / Presicce, P., Cappelletti, M., Morselli, M., Ma, F., Senthamaraikannan, P., Protti, G., Nadel, B.B., Aryan, L., Eghbali, M., Salwinski, L., Pithia, N., De Franco, E., Miller, L.A., Pellegrini, M., Jobe, A.H., Chougnet, C.A., Kallapur, S.G.. - In: ISCIENCE. - ISSN 2589-0042. - 26:11(2023). [10.1016/j.isci.2023.108118]
Amnion responses to intrauterine inflammation and effects of inhibition of TNF signaling in preterm Rhesus macaque
Morselli M.;
2023-01-01
Abstract
Intrauterine infection/inflammation (IUI) is a frequent complication of pregnancy leading to preterm labor and fetal inflammation. 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 lipopolysaccharide with human cohorts of chorioamnionitis. Bulk RNA sequencing (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 nuclear factor KB (NF-kappa B) signaling and reversed by the anti-tumor necrosis factor (TNF) antibody Adalimumab. Inhibition of collagen biosynthesis by IUI was partially restored by Adalimumab. Interestingly, single-cell transcriptomics, flow cytometry, and immunohistology 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
