Untersuchung der endometrialen Epithelzell-junctions und der Trophoblast-endometrialen Interaktion im 3D-Zellkultursystem

Autor: Buck, Volker Uwe
Přispěvatelé: Classen-Linke, Irmgard
Jazyk: němčina
Rok vydání: 2013
Předmět:
Zdroj: Aachen : Publikationsserver der RWTH Aachen University 127 Bl. : Ill., graph. Darst. (2013). = Aachen, Techn. Hochsch., Diss., 2013
Popis: The implantation of the blastocyst only occurs during the receptive phase of the endometrium, the so called ‘implantation window’. It represents a critical step in early pregnancy. Aim of this study was to investigate the redistribution of lateral cell-cell junctions of endometrial epithelial cells and its importance for endometrial receptivity and the invasion of the trophoblast in the early phase of pregnancy. The study is composed of three parts: 1) Examination of human endometrial tissue samples from different phases of the menstrual cycle with focus on the redistribution of adhering junctions in preparation for trophoblast invasion: Subject to the menstrual cycle, markers of desmosomes (desmoplakin, desmoglein 2, plakoglobin) and adherens junctions (E-cadherin, beta-catenin) were redistributed from a subapical concentration to an equal distribution along lateral membranes of glandular epithelial cells. This redistribution was correlated with the onset of the implantation window. 2) Studies on a DSG2-mutant mouse strain as a model for desmosomal defects: In an experimental study, the uteri of mice carrying a mutation in the DSG2-gene due to a deletion of exons 4 to 6 were examined. Compared to wild type mice the immunofluorescence signal of the desmosomal cadherin desmoglein 2 was strongly diminished in endometrial epithelial cells of mutant animals. In addition, the number of punctuate staining spots of desmoglein 2 and the desmosomal plaque protein desmoplakin was decreased along the lateral membranes of the glandular epithelium. 3) Establishment of a 3D cell culture model to investigate trophoblast-endometrial interactions: In order to investigate the regulation of junction-specific trophoblast-endometrial interactions a new 3D cell culture system was established. Four differently polarized endometrial epithelial cell lines were cultured in a Matrigel matrix and formed gland-like spheroids. According to their different polarity the four cell lines showed a different distribution of desmoplakin along their lateral membranes. In addition, by confronting the 3D culture with the trophoblast cell line AC-1M88, interactions between these cells and the endometrial spheroids via cell-cell junctions could be demonstrated as well as invasion of these gland-like structures by the trophoblast cells. The data presented in this study point to a cyclic regulation of endometrial junctions that in preparation for implantation might have an effect on the trophoblast-endometrial interactions. The regulation of these interactions by ovarian steroids can be further investigated in the newly established 3D cell culture system.
Databáze: OpenAIRE
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