Regulatory effects of corpus luteum and relaxin on the human decidua

最近的研究表明，妊娠期和妊娠早期黄体缺失与妊娠期高血压疾病（如先兆子痫）发生风险增加有关。这对于那些在所谓的人工周期中作为辅助生殖冷冻胚胎移植的一部分进行治疗的妇女来说尤其重要。去个体化受损在该疾病的发病机制中起重要作用。蜕膜控制着胚胎着床、滋养细胞侵袭和血管适应妊娠的重要调控过程。黄体及其分泌产物松弛素的缺失对蜕膜特性的影响程度以及蜕膜与滋养细胞和内皮细胞的相互作用将在本项目中进行研究。为此，研究人员使用了原代人子宫内膜基质细胞（hESC），这些细胞是从可生育受试者的子宫内膜活检中分离出来的，也从模拟治疗中分离出来的，模拟治疗是在有或没有黄体的情况下对接受生育治疗的女性进行的。除了研究hESC的功能和分子生物学特性外，研究hESC与其靶细胞的相互作用也是本项目的重点。因此，hESC的细胞外囊泡在功能和转录组水平上都具有特征。通过沉默或过表达特异性非编码rna修饰细胞外囊泡后，在2D和3D体外模型中检测其对滋养细胞和内皮细胞的影响。该项目的研究结果将为先兆子痫的病理生理学提供新的见解，并将为开发早在妊娠期就恢复脆弱妇女个体体内平衡的方法提供基础。

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.