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Selected Publication:

Greimel, PH.
DIFFERENTIAL EXPRESSION OF METALLOPROTEINASES AND THEIR SPECIFIC INHIBITORS IN DELAYED MISCARRIAGE VERSUS CONTROLS - A WIDE SPECTRUM SCREENING FOR MMPs, ADAMs, ADAM-TSs AND TIMPs IN FIRST TRIMESTER PLACENTAL TISSUE
[ Diplomarbeit ] Medical University of Graz; 2011. pp. 59 [OPEN ACCESS]
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Authors Med Uni Graz:
Greimel Patrick
Advisor:
Desoye Gernot
Hiden Ursula
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Abstract:
Abstract The establishment of pregnancy in humans is a complex and tightly regulated event. Central for fetal and maternal survival is the proper development and functioning of the placenta. Mainly responsible for the development of placental structures and the functional bonding of the two organisms is a specialised cell lineage, the trophoblast. Trophoblastic cells start to invade maternal tissue in early first trimester of pregnancy, thereby degrading extracellular matrix (ECM). This strictly governed process is dependend on ECM degrading metalloproteinases, namely the groups of MMPs (matrix metalloproteinases), ADAMs (a disintegrin and metalloproteinases), ADAM-TSs (a disintegrin and metalloproteinases with trombospondin motif), while specific inhibition is provided by TIMPs (tissue inhibitors of metalloproteases). A common pathology in early pregnancy is the fetal death with absent expulsion from the uterus, which is defined as delayed miscarriage. In our study we aimed to detect a possible association between delayed miscarriage and altered metalloprotease expression. First trimester placental tissue of women suffering from delayed miscarriage and controls from legal pregnancy interruptions carried out for psycho-social reasons was obtained. RNA was isolated and PCR screening for all relevant enzymes was performed subsequently. Results were regarded as significant at p<0.05. In summary, it can be stated that there is a strong trend of metalloprotease upregulation under pathologically altered conditions. Further, it was possible to detect significant differences particularly in gestational weeks 7 and 8. This is the first wide spectrum screening for all relevant members of the metalloprotease family in first trimester trophoblasts. We could demonstrate the expression of several previously unknown metalloproteinases in human trophoblasts, thus enabling us to underline the importance of these enzymes involved in crucial developmental events. In consideration of significant protease upregulation in early first trimester, this is a new approach to identify mechanisms of delayed miscarriage.

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