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Abstract
Problem
During pregnancy, the decidual spiral arterioles (SpAs) that supply maternal blood to the placenta undergo a series of changes to optimise the transfer of nutrients and oxygen to the developing foetus. Recent studies have shown that initiation of SpA transformation coincides with decidual leucocyte infiltration. Leucocytes are known to be a source of matrix metalloproteinases (MMPs); however, the complete profile of MMPs expressed by decidual NK cells (dNK) and macrophages has not been characterised. We hypothesised that leucocyte‐derived MMPs contribute to SpA remodelling.
Methods
Decidual NK cells and macrophages were isolated from first trimester decidua and their MMP repertoire profiled by qRT‐PCR (n = 10; 5‐11 weeks). Dual immunofluorescence was used to localise MMP expression in situ (n = 3; 5‐12 weeks). Gelatin zymography was carried out to assess whether leucocyte‐derived MMPs can degrade ECM. In situ zymography and immunofluorescence identified MMP activity in tissue‐resident dNK and macrophages.
Results
Decidual NK cells cells and macrophages expressed MMP2, ‐7, ‐9, ‐11, ‐16, ‐19 and tissue inhibitors of metalloproteinase‐1, ‐2, and ‐3. Both cell types degraded gelatin using MMP2 and MMP9 and broke down collagen in an in vitro model of the SpA. Extravillous trophoblasts (EVTs) expressed a similar repertoire of MMPs.
Conclusion
We suggest that matrix remodelling in SpA is initiated by infiltrating leucocytes, while EVTs become involved at later stages.
During pregnancy, the decidual spiral arterioles (SpAs) that supply maternal blood to the placenta undergo a series of changes to optimise the transfer of nutrients and oxygen to the developing foetus. Recent studies have shown that initiation of SpA transformation coincides with decidual leucocyte infiltration. Leucocytes are known to be a source of matrix metalloproteinases (MMPs); however, the complete profile of MMPs expressed by decidual NK cells (dNK) and macrophages has not been characterised. We hypothesised that leucocyte‐derived MMPs contribute to SpA remodelling.
Methods
Decidual NK cells and macrophages were isolated from first trimester decidua and their MMP repertoire profiled by qRT‐PCR (n = 10; 5‐11 weeks). Dual immunofluorescence was used to localise MMP expression in situ (n = 3; 5‐12 weeks). Gelatin zymography was carried out to assess whether leucocyte‐derived MMPs can degrade ECM. In situ zymography and immunofluorescence identified MMP activity in tissue‐resident dNK and macrophages.
Results
Decidual NK cells cells and macrophages expressed MMP2, ‐7, ‐9, ‐11, ‐16, ‐19 and tissue inhibitors of metalloproteinase‐1, ‐2, and ‐3. Both cell types degraded gelatin using MMP2 and MMP9 and broke down collagen in an in vitro model of the SpA. Extravillous trophoblasts (EVTs) expressed a similar repertoire of MMPs.
Conclusion
We suggest that matrix remodelling in SpA is initiated by infiltrating leucocytes, while EVTs become involved at later stages.
Original language | English |
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Pages (from-to) | e13054 |
Journal | American Journal of Reproductive Immunology |
Early online date | 29 Sept 2018 |
DOIs | |
Publication status | Published - 2018 |
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Maternal & Fetal Health Research Centre
Stevens, A. (PI), Heazell, A. (PI), Tower, C. (PI), Brison, D. (PI), Johnstone, E. (PI), Cottrell, E. (PI), Mann, E. (PI), Ingram, E. (PI), Crocker, I. (PI), Chernyavsky, I. (PI), Myers, J. (PI), Aplin, J. (PI), Higgins, L. (PI), Harris, L. (PI), Dilworth, M. (PI), Westwood, M. (PI), Whitworth, M. (PI), Desforges, M. (PI), Brownbill, P. (PI), Ruane, P. (PI), Sturmey, R. (PI), Worton, S. (PI), Greenwood, S. (PI), Sibley, C. (PI) & Belchamber, K. (PI)
1/09/18 → 31/12/35
Project: Research