Regulatory effects of corpus luteum and relaxin on the human decidua

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Recent studies suggest that the absence of the corpus luteum at conception and early in pregnancy is associated with an increased risk of developing hypertensive disorders of pregnancy, e.g. preeclampsia. This is particularly important for women who are treated in so-called artificial cycles as part of a frozen embryo transfer in assisted reproduction. Impaired decidualization plays an important role in the pathogenesis of the disease. The decidua controls important regulatory processes of embryo implantation, trophoblast invasion and vascular adaptation to pregnancy. The extent to which the absence of the corpus luteum and its secretion product relaxin influence decidual characteristics and the decidual interaction with trophoblasts and endothelial cells is to be investigated in this project. For this purpose, primary human endometrial stromal cells (hESC) are used, which were isolated from endometrial biopsies of fertile subjects as well as from mock treatments, which were performed in the presence or absence of a corpus luteum in women undergoing fertility treatment. In addition to the characterization of functional and molecular-biological properties of hESC, research of the interaction between hESC and their target cells is the focus of this project. Thereby, extracellular vesicles from hESC are characterized functionally as well as on transcriptome level. After modification of extracellular vesicles by silencing or overexpression of specific non-coding RNAs their influence on trophoblasts and endothelial cells is examined in 2D and 3D in vitro models. Findings from this project will provide new insights into the pathophysiology of preeclampsia and will provide the basis for the development of methods to restore decidual homeostasis in vulnerable women as early as the periconceptional period.