Modeling human ectopic pregnancies with trophoblast and vascular organoids

• DOI: 10.1016/j.celrep.2023.112546
• Publication Date: 2023-05-23T11:24:00Z
• Authors: Xiaoya Zhao; Zhenwu Zhang; Qian Zhu; Yurui Luo; Qinying Ye; Shuxiang Shi; Xueyang He; Jing Zhu; Duo Zhang; Wei Xia; Yiqin Zhang; Linlin Jiang; Long Cui; Yinghui Ye; Yangfei Xiang; Junhao Hu; Jian Zhang; Chao-Po Lin
• Keywords: Organoids; CP: Stem cell research; QH301-705.5; Pregnancy; Placenta; Humans; Female; Embryo Implantation; Biology (General); 3. Good health; Trophoblasts; Pregnancy, Ectopic

Ruptured ectopic pregnancy (REP), a pregnancy complication caused by aberrant implantation, deep invasion, and overgrowth of embryos in fallopian tubes, could lead to rupture of fallopian tubes and accounts for 4%-10% of pregnancy-related deaths. The lack of ectopic pregnancy phenotypes in rodents hampers our understanding of its pathological mechanisms. Here, we employed cell culture and organoid models to investigate the crosstalk between human trophoblast development and intravillous vascularization in the REP condition. Compared with abortive ectopic pregnancy (AEP), the size of REP placental villi and the depth of trophoblast invasion are correlated with the extent of intravillous vascularization. We identified a key pro-angiogenic factor secreted by trophoblasts, WNT2B, that promotes villous vasculogenesis, angiogenesis, and vascular network expansion in the REP condition. Our results reveal the important role of WNT-mediated angiogenesis and an organoid co-culture model for investigating intricate communications between trophoblasts and endothelial/endothelial progenitor cells.