Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Weiss, G.
Trophoblast invasion during the first trimester of human pregnancy
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Graz Medical University; 2015. pp.72.
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- Autor*innen der Med Uni Graz:
- Weiss Gregor
- Betreuer*innen:
- Desoye Gernot
- Huppertz Berthold
- Moser Gerit
- Altmetrics:
- Abstract:
- Invasion of extravillous trophoblasts (EVT) during human pregnancy is tightly linked to appropriate cell to cell contact of EVT and spiral arteries, conducted by locally expressed cytokines. This process is mandatory for successful development of placenta and embryo/fetus. In this project the interaction of the first trimester trophoblast derived cell line ACH-3P with adult iliac arterial (AEC) and venous endothelial cells (VEC) was investigated. The impact of ACH-3P conditioned media (Cdm), obtained at 2.5% and 21% oxygen, on endothelial cell viability (LDH-Assay) and network formation (Matrigel-Assay) was tested. The cytokine expression of AEC- and VEC-Cdm was examined and results were confirmed with ELISA analysis. Furthermore the influence of Cdm on ACH-3P proliferation, invasion and mitochondrial activity was examined. Additionally, direct co-culture experiments with ACH-3P and AEC on Matrigel were performed and the morphology, migration and cytokine expression pattern of ACH-3P under different oxygen concentrations was investigated. ACH-3P-Cdm significantly enhanced cell viability of AEC and VEC after 72 h. ACH-3P-Cdm at 2.5% oxygen stabilized endothelial network structures in Matrigel up to 24 h, similar to the effect of a direct co-culture of AEC and ACH-3P. ACH-3P more likely invaded towards AEC-Cdm than towards VEC-Cdm. AEC- and VEC-Cdm reduced ACH-3P cell proliferation after 24 h of culture and decreased mitochondrial activity under 2.5% oxygen. AEC-Cdm achieved this effect also at 8% and 21% oxygen. AEC and VEC showed a similar pattern of secreted cytokines. However, elevated levels of cytokines secreted by AEC were found for GRO, IL-6, MMP-1 and uPAR. ELISA confirmed elevated concentrations of IL-6 and uPAR in AEC compared to VEC. ACH-3P morphology did not differ within different oxygen concentrations. ACH-3P showed best migration at 8% oxygen. Cytokine expression pattern revealed elevated levels of I-TAC, MCP-3, MCP-4, MMP-1, uPAR, VEGFR-2 and VEGFR-3 under 2.5% oxygen; Angiogenin, ENA-78 and bFGF under 8% oxygen and PlGF and Tie-2 under 21% oxygen. The presented results clearly demonstrate that cytokines of both cell types, AEC and ACH-3P, differentially contribute to successful guidance and interaction in the process of trophoblast invasion.