Placental glycocode signalling networks in preeclampsia: Implications for maternal and foetal health

先兆子痫中的胎盘糖码信号网络：对孕产妇和胎儿健康的影响

• 批准号: 397472343
• 负责人: Professorin Dr. Sandra Maria Blois
• 金额: --
• 依托单位: Klinik für Geburtshilfe und Pränatalmedizin
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/397472343?language=en
• 关键词: Placental; glycocode; signalling; networks; preeclampsia

The placenta is a transitory organ whose proper development and function ensures foetal survival. Placental development involves a complex interaction between maternal cells and heavily glycosylated foetal trophoblasts; failure of this process can cause preeclampsia (PE), a life-threatening, heterogeneous pregnancy disorder. Galectin-1 (gal-1) is a versatile translator of the glycocode, involved in regulating key reproductive processes (placentation, immune tolerance and angiogenesis). Indeed, human and animal studies have shown that dysregulation of gal-1 plays a unique role during PE pathogenesis; gal-1 is downregulated in the placenta and serum of human PE patients, and gal-1 deficient pregnant mice spontaneously develop PE-like symptoms. Further, these mice have an altered placental glycocode, placenta insufficiency and growth restricted foetuses. These data suggest that a more in-depth analysis of glycocode/galectin signalling networks in pregnancy may help to define the routes through which PE develops, offering opportunities to design new diagnosis and disease management strategies. This project seeks to crack the placental glycocode, unravelling the structural frameworks and recognition strategies of sugar-based interactions in placental niche that relate to both health and PE disease. We further aim to identify placental/maternal factors that drive PE heterogeneity using new animal models of foetal/placental-trophoblast or maternal/decidua gal-1 deficiency. Additionally, we aim to characterise the specific galectin signature that contributes to PE heterogeneity. Since the glycocode is concerted interplay of a multitude of factors, unravelling the placental glycocode will potentially contribute to the development of novel, glycan based, early diagnostic biomarkers.

胎盘是一个短暂的器官，其适当的发育和功能保证了胎儿的存活。胎盘发育涉及母体细胞和高度糖化的胎儿滋养层细胞之间的复杂相互作用；这一过程的失败可导致先兆子痫(PE)，这是一种威胁生命的异质性妊娠障碍。Galectin-1(GAL-1)是糖码的通用翻译者，参与调节关键的生殖过程(胎盘形成、免疫耐受和血管生成)。事实上，人类和动物的研究表明，GAL-1的调节失调在PE的发病机制中起着独特的作用；GAL-1在人类PE患者的胎盘和血清中表达下调，GAL-1缺陷的怀孕小鼠自发地出现PE样症状。此外，这些小鼠的胎盘糖码改变，胎盘功能不全，胎儿生长受限。这些数据表明，对妊娠期糖码/半乳糖凝集素信号网络的更深入分析可能有助于确定PE发生的途径，为设计新的诊断和疾病管理策略提供机会。该项目旨在破解胎盘糖码，解开胎盘利基中与健康和PE疾病相关的糖基相互作用的结构框架和识别策略。我们的进一步目标是使用新的胎盘/胎盘滋养细胞或母体/蜕膜GAL-1缺乏的动物模型来确定驱动PE异质性的胎盘/母体因素。此外，我们的目标是描述导致PE异质性的特定半乳糖凝集素特征。由于糖码是多种因素共同作用的结果，解开胎盘糖码可能有助于开发新的、基于糖链的早期诊断生物标记物。