M Siwetz

Publications (4)19.32 Total impact

• Article: Placental expression of d-chiro-inositol phosphoglycans in preeclampsia.

  M Scioscia, M Siwetz, F Fascilla, B Huppertz
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  ABSTRACT: Abnormalities in glucose metabolism linked to d-chiro-inostol phosphoglycans (IPGs) have been described in human placentas of preeclamptic women. In this study, a semi-quantitative approach to assess the histological assessment of IPGs revealed no significant differences between early and late onset preeclampsia and gestational age matched controls. However, there was a tendency towards higher values in early onset preeclampsia for villous stroma and placental vessels. Moreover, in control cases staining of plasma in placental vessels was present only in one part of vessels of mature intermediate villi while in preeclamptic specimens all placental vessels showed a similar staining. The tendencies of more staining in villous stroma associated with a differential staining of placental vessels only in preeclamptic specimens support a vectoral movement of d-chiro-inositol phosphoglycans from the fetus to the placenta.
  Placenta 07/2012; 33(10):882-4. · 3.69 Impact Factor
• Article: The art of identification of extravillous trophoblast.

  G Moser, K Orendi, M Gauster, M Siwetz, C Helige, B Huppertz
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  ABSTRACT: Immunohistochemical staining with specific markers for the respective cell type facilitates tracking and identification of cells such as extravillous trophoblast in the uterine wall. Cytokeratin has been recommended as a marker for all kinds of trophoblasts and is commonly used as a marker to identify interstitial as well as endovascular trophoblast. With immunohistochemical double staining of specimens of first trimester placental bed we show that staining with anti-cytokeratin alone is not sufficient to track all routes of trophoblast invasion. Endovascular trophoblasts can be easily mixed up with endoglandular trophoblasts. Thus, additional application of specific markers for extravillous trophoblast such as anti-HLA-G is strongly recommended, ideally in combination with other markers in immunohistochemical or immunofluorescence double staining.
  Placenta 02/2011; 32(2):197-9. · 3.69 Impact Factor
• Article: Caspases rather than calpains mediate remodelling of the fodrin skeleton during human placental trophoblast fusion.

  M Gauster, M Siwetz, K Orendi, G Moser, G Desoye, B Huppertz
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  ABSTRACT: Fusion of cytotrophoblasts with the overlying syncytiotrophoblast is an integral step in differentiation of the human placental villous trophoblast. Multiple factors, such as growth factors, hormones, cytokines, protein kinases, transcription factors and structural membrane proteins, were described to modulate trophoblast fusion. However, the knowledge on remodelling of the membrane-associated cytoskeleton during trophoblast fusion is very limited. This study describes the link between remodelling of spectrin-like alpha-fodrin and intercellular trophoblast fusion. Experiments with primary trophoblasts isolated from term placentas and the choriocarcinoma cell line BeWo revealed a biphasic strategy of the cells to achieve reorganization of alpha-fodrin. Syncytialization of trophoblasts was accompanied by down-regulation of alpha-fodrin mRNA, whereas the full-length alpha-fodrin protein was cleaved into 120 and 150 kDa fragments. Application of calpeptin and calpain inhibitor III did not affect alpha-fodrin fragmentation in primary term trophoblasts and forskolin-treated BeWo cells, but decreased secretion of beta human chorionic gonadotropin. In contrast, inhibitors of caspases 3, 8 and 9 attenuated generation of the 120 kDa fragment and a general caspase inhibitor completely blocked fragmentation, suggesting an exclusive function of caspases in alpha-fodrin remodelling. Immunofluorescence double staining of human placenta revealed co-localization of active caspase 8 with alpha-fodrin positive vesicles in fusing villous cytotrophoblasts. These results suggest that caspase-dependent fragmentation of alpha-fodrin may be important for reorganization of the sub-membranous cytoskeleton during trophoblast fusion.
  Cell death and differentiation 10/2009; 17(2):336-45. · 8.24 Impact Factor
• Article: Fusion of villous trophoblast can be visualized by localizing active caspase 8.

  M Gauster, M Siwetz, B Huppertz
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  ABSTRACT: Villous cytotrophoblast differentiation and subsequent fusion with the overlying syncytiotrophoblast depend on multiple factors such as growth factors, cytokines, hormones, protein kinases, transcription factors, structural membrane proteins and proteases. Caspase 8, an aspartate-specific cysteine protease, is mainly known for its role in programmed cell death, but was also demonstrated to be crucial for villous trophoblast differentiation. This study aimed to localize active caspase 8 in the villous trophoblast layer of human first trimester placenta. To this end, immunofluorescence double staining was performed, using a monoclonal rabbit antibody against cleaved caspase 8 in combination with antibodies against cytokeratin 7, chorionic gonadotropin beta subunit (beta hCG), beta-actin, placental protein 13 (PP13), alpha-fodrin and Ki-67. Immunofluorescence revealed cleaved caspase 8 in one out of 422 villous cytotrophoblasts resting on the basement membrane, in one out of 759 perinuclear regions within the syncytiotrophoblast and in few trophoblasts located between these two layers. Double staining of cleaved caspase 8 and Ki-67 antigen revealed that caspase 8 is activated only in cytotrophoblasts which have left the cell cycle. The staining suggests that caspase 8 is activated in villous cytotrophoblasts just prior to fusion of these cells and escorts the nuclei from the mononucleated to the syncytial state.
  Placenta 05/2009; 30(6):547-50. · 3.69 Impact Factor