Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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Gewählte Publikation:

Eyth, C.
Temporal and spatial localisation of Matrix Metalloproteinase 12 positive trophoblast cells in the development of the human placenta.
[ Diplomarbeit ] Medical University of Graz; 2012. pp. 131 [OPEN ACCESS]
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Autor*innen der Med Uni Graz:
Betreuer*innen:
Ghaffari Tabrizi-Wizsy Nassim
Kresse Adelheid
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Abstract:
Introduction: The physiological development of the human placenta shares close similarities to the invasive behaviour of a progressing malignant tumour. In contrast to the tumour, the placenta is under control of its almost unlimited invasive potential by a strict regulation program. Human placentation as a highly interesting model for controlled invasion is therefore in the focus of research, unveiling a plethora of factors acting pro-invasive as the versatile family of matrixins. Macrophage elastase (MMP-12), which was recently described in the placenta is probably involved in spiral artery remodelling, but shows also a broad range of features regarding progression, invasion, metastasis and angiogenesis in malignant tumours. The spatial and temporal localisation of this particular member is the content of this thesis. Material & Methods: Previous data obtained from an U95A GeneChip microarray showed a highly significant upregulation of MMP-12 in isolated first trimester trophoblast (FT) compared to term trophoblast cells. Radioactive and non-radioactive in-situ hybridization as well as double-label fluorescence immunohistochemistry utilizing MMP-12 antibodies versus HLA-G, CK-7, CD34 and CD68 were used for spatial detection and identification on the RNA- as well as the protein level. Quantitative and statistical evaluation was performed by subsequent computer aided analysis of the expression density over the course of the first trimester. Results: We showed that MMP-12 expression and translation into the protein product takes place in a subpopulation of extravillous cytotrophoblast cells (evCTB), proofed on the base of HLA-G positivity. A decrease of MMP-12 mean density was noticed from 0.38 to 0.35 at early and middle down to 0.23 at late FT. No expression was detected in placental site giant cells and, in contrast to previously published data, MMP-12 was not present in vCTB. Decidual vessels and glands exhibited unexpectedly high signal levels and furthermore showed trophoblast plugging from the 6th week of pregnancy. Conclusion: Our data showed congruent data regarding the spatial localisation on the mRNA and protein level and also a clear tendency in the decrease of signal density towards the end of the first trimester and as against term. As a foundation for conducting functional assays, these data might promise deeper insights in the mechanism of trophoblast invasion and the understanding of the development of the human placenta.

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