DETECT · Deciphering the molecular mechanisms of Ectopic pregnancy using Transcriptomics and Exploring Cellular Trophoblast invasion

Ectopic pregnancy affects ~2% of pregnancies and is the leading cause of death in the first trimester. It occurs when the embryo implants outside the uterus, often in the fallopian tube. Placentation, a critical process for pregnancy success, is severely disrupted in ectopic pregnancy. The dysregulated trophoblast invasion in an unsuitable environment can lead to tissue rupture and life-threatening maternal bleeding. Despite its severity, the molecular mechanisms underlying placentation and its dysregulation in ectopic pregnancy are poorly understood. This proposal aims to uncover these mechanisms by combining cutting-edge transcriptomics technologies and computational methods. The project involves three main objectives: [1] Generate the first single-cell and spatial transcriptome atlas of ectopic pregnancy, profiling uterine and fallopian tube samples from donors with typical (eutopic) and ectopic pregnancies between 5-8 post-conceptional weeks. [2] Develop a novel computational framework, MultiCell, to identify differences between eutopic and ectopic pregnancies in molecular mechanisms supporting trophoblast invasion, integrating cellular metabolism, cell-cell communication, and signaling. [3] Validate the effect of identified molecules on trophoblast invasion using trophoblast organoid models. By comprehensively profiling cell types and their spatial organization in both conditions, and developing new computational tools to analyze these data, this research will provide unprecedented insights into the molecular basis of placentation and trophoblast invasion in eutopic and ectopic pregnancies. The project's findings could lead to improved preventive tools and treatments in multiple pregnancy complications where trophoblast invasion is dysregulated, contributing to reducing the incidence of this life-threatening condition and advancing our understanding of the female reproductive system and early pregnancy.