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

• Applicant: Professorin Dr. Sandra Maria Blois
• Subject Area: Gynaecology and Obstetrics ; Reproductive Medicine, Urology
• Term: from 2018 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 397472343

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.

• DFG Programme: Research Grants