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Am J Reprod Immunol. 2019 Jan;81(1):e13054. doi: 10.1111/aji.13054. Epub 2018 Sep 29.

Decidual leucocytes infiltrating human spiral arterioles are rich source of matrix metalloproteinases and degrade extracellular matrix in vitro and in situ.

Author information

1
Maternal and Fetal Health Research Centre, Institute of Human Development, The University of Manchester, Manchester, UK.
2
Academic Health Science Centre, St Mary's Hospital, Manchester, UK.
3
Research Centre for Women's and Infants' Health, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
4
Manchester Pharmacy School, University of Manchester, Manchester, UK.

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.

KEYWORDS:

decidua; decidual natural killer; extracellular matrix; extravillous trophoblast; macrophage; matrix metalloproteinase; remodelling; spiral arterioles

PMID:
30267451
DOI:
10.1111/aji.13054

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