Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Gorsek Sparovec, T.
Characterization of Placenta accreta spectrum disorders
PhD-Studium (Doctor of Philosophy); Humanmedizin; [ Dissertation ] Medizinische Universität Graz; 2023. pp.
- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Gold ehem Ulrich Daniela
- Huppertz Berthold
- Altmetrics:
- Abstract:
- The endometrium is regenerated from endometrial mesenchymal stem cells (eMSC) and decidualized when exposed to circulating estrogen and progesterone before implantation. In placenta accreta spectrum (PAS), placental-maternal interface is aberrant and displays absence of decidua, abnormal vasculature, presence of scar tissue, and abnormal extravillous trophoblast invasion. The aim of this thesis was to investigate how the PAS microenvironment affects the characteristics abundance and functionality of eMSC. Secondary aim was to characterize the transcriptomic profile of the placental bed microenvironment to better understand the underlying mechanisms of PAS. To investigate differences in eMSC properties, we analyzed biopsies from patients with PAS (PAS, n=7), pregnant controls at the time of cesarean section (P, n=11), 1st trimester decidual samples (1st trim, n=9) and non-pregnant control patients through endometrial biopsy (NP, n=15). The fraction of SUSD2+ eMSC was determined on histological sections by immunohistochemistry and in vitro after eMSC isolation. The functional properties of the isolated SUSD2+ eMSC were examined by colony forming unit assay (CFU) and differentiation into various mesenchymal lineage cells as well as decidual stromal cells. In addition, we investigated changes in mesenchymal membrane markers and mesenchymal gene expression patterns in decidualized SUSD2+ eMSC. Biopsies from the placental bed of PAS (n=7) and pregnant controls (n=8) were used for transcriptomic profiling using bulk RNA sequencing (RNA-seq). Differential expression was performed by DESeq2, followed by the GO term and Kegg pathway analysis. Histological sections showed significantly lower SUSD2+ eMSC abundance in P and PAS (p < 0.048 and 0.0012, respectively). In vitro, the fraction of SUSD2+ eMSC was significantly lower only in PAS (3,6%, p < 0.0302) in comparison to P and NP groups (13,8% and 16,6%, respectively). SUSD2+ eMSC in P and NP display similar functional capacities in terms of differentiation and CFU. However, we detected significantly higher CFU in first subcloning in PAS (p < 0.01) indicating higher proliferative capacity of eMSC in PAS. Transcriptome analysis resulted in 807 differentially expressed genes, which were associated to wound healing, TGFβ receptor binding, protein binding, cell growth and proliferation, epithelial to mesenchymal transition and angiogenesis. PAS microenvironment exhibits dysregulation in TGFβ signaling pathways and pathways involved in extracellular matrix organization with several similarities to scar tissue. In conclusion, this work contributes to a better understanding of the underlying pathomechanisms of PAS and their effects on endometrial stem cells.