Regulatory effects of corpus luteum and relaxin on the human decidua

黄体和松弛素对人体蜕膜的调节作用

• 批准号: 537607142
• 负责人: Professorin Dr. Alexandra P. Bielfeld
• 金额: --
• 依托单位: Klinik für Frauenheilkunde und Geburtshilfe
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/537607142?language=en
• 关键词: Regulatory; effects; corpus; luteum; relaxin

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.

最近的研究表明，怀孕和怀孕早期黄体缺失与患妊娠期高血压疾病的风险增加有关，例如先兆子痫。对于在辅助生殖中作为冷冻胚胎移植一部分在所谓的人工周期中接受治疗的女性来说，这一点尤其重要。蜕膜受损在该病的发病机制中起着重要作用。蜕膜控制着胚胎着床、滋养层侵袭和血管对妊娠的适应等重要调控过程。黄体及其分泌产物松弛素的缺失对蜕膜特性以及蜕膜与滋养层细胞和内皮细胞的相互作用的影响程度将在本项目中进行研究。为此，使用了原代人类子宫内膜间质细胞(HESC)，这些细胞是从生育受试者的子宫内膜活检组织中分离出来的，也是从模拟治疗中分离出来的，这些组织是在接受生育治疗的妇女在有或没有黄体的情况下进行的。除了鉴定hESC的功能和分子生物学特性外，研究hESC与其靶细胞之间的相互作用也是本项目的重点。因此，hESC的胞外小泡在功能和转录组水平上都得到了鉴定。在2D和3D体外模型中，通过沉默或过度表达特定的非编码RNA来修饰细胞外小泡后，它们对滋养层细胞和内皮细胞的影响被检测。该项目的发现将为先兆子痫的病理生理学提供新的见解，并将为开发方法以恢复脆弱妇女的蜕膜动态平衡提供基础。