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

胎盘是一个过渡性器官，其正常的发育和功能确保了胎儿的存活。胎盘发育涉及母体细胞和高度糖基化的胎儿滋养层细胞之间的复杂相互作用;这一过程的失败可能导致先兆子痫（PE），这是一种危及生命的异质性妊娠疾病。半乳糖凝集素-1（gal-1）是糖密码子的多功能翻译者，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，人类和动物研究表明，gal-1的失调在PE发病过程中发挥独特的作用; gal-1在人类PE患者的胎盘和血清中下调，gal-1缺陷的妊娠小鼠自发地出现PE样症状。此外，这些小鼠具有改变的胎盘糖码、胎盘功能不全和生长受限胎仔。这些数据表明，对妊娠期糖码/半乳糖凝集素信号网络进行更深入的分析可能有助于确定PE发展的途径，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，揭示与健康和PE疾病相关的胎盘生态位中基于糖的相互作用的结构框架和识别策略。我们进一步的目的是确定胎盘/母体因素，驱动PE异质性使用新的动物模型的胎儿/胎盘滋养层或母体/蜕膜半乳糖醛酸-1缺乏症。此外，我们的目标是确定特定的半乳糖凝集素的签名，有助于PE异质性。由于糖码是多种因素的协同相互作用，解开胎盘糖码将可能有助于开发新的、基于聚糖的早期诊断生物标志物。

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.