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Medizinische Universität Graz

PI, Huppertz

Aponecrotic release of subcellular fragments from the trophoblast in PE

 

Aponecrotic release of subcellular fragments from the trophoblast is one of the main features of PE, while failure in trophoblast invasion is one of the main features of fetal growth restriction (FGR). Pregnancy is an immunological and inflammatory challenge for the mother, as non-self placental cellular debris needs to be dealt with throughout pregnancy. The etiologies of PE and FGR have been refined a couple of years ago while respective new developments in research on the topic are still missing (1). The main focus of this study is to identify the pathways and mechanisms within the placental syncytiotrophoblast that lead to the release of aponecrotic fragments into the maternal circulation and how they interfere with the maternal inflammatory system (2, 3). Placenta-specific biomarkers are released from the syncytiotrophoblast and can be used as predictors to develop preeclampsia (4, 5). Their expression patterns (AH) will be used as a surrogate for the proper development of the trophoblast in PE. Experiments will be carried out using placental villous explants (tissue cultures), isolated primary cells from the human placenta (first trimester and term) as well as trophoblast-derived cell lines for transfection/silencing experiments (GD, DU, CW). The student will be trained in placental biology and will receive insights in the turnover of placental trophoblast and its effect on maternal endothelial cell function. In addition, the student will get background knowledge on current concepts of the etiologies of PE and FGR and where demands for future research exist (DU, KMP).

1. Huppertz B. Placental origins of preeclampsia: challenging the current hypothesis. Hypertension. 2008;51:970-5. doi: 10.1161/HYPERTENSIONAHA.107.107607

2. Huppertz B. Maternal and fetal factors and placentation: implications for pre-eclampsia. Pregnancy Hypertens. 2014;4:244. doi: 10.1016/j.preghy.2014.04.015

3. Huppertz B, Weiss G, Moser G. Trophoblast invasion and oxygenation of the placenta: measurements versus presumptions. J Reprod Immunol 2014;101-102:74-9. doi: 10.1016/j.jri.2013.04.003

4. Huppertz B, Meiri H, Gizurarson S, Osol G, Sammar M. Placental protein 13 (PP13): a new biological target shifting individualized risk assessment to personalized drug design combating pre-eclampsia. Hum Reprod Update 2013;19:391-405. doi: 10.1093/humupd/dmt003

5. Huppertz B. Maternal-fetal interactions, predictive markers for preeclampsia, and programming. J Reprod Immunol 2015;108:26-32. doi: 10.1016/j.jri.2014.11.003

 

 

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