Modeling human ectopic pregnancies with trophoblast and vascular organoids
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
Affiliations
Xiaoya Zhao
Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, No. 910, Hengshan Road, Shanghai 200030, China; Shanghai Municipal Key Clinical Specialty, Shanghai, China
Zhenwu Zhang
School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
Qian Zhu
Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, No. 910, Hengshan Road, Shanghai 200030, China; Shanghai Municipal Key Clinical Specialty, Shanghai, China
Yurui Luo
School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
Qinying Ye
School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
Shuxiang Shi
School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
Xueyang He
Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China
Jing Zhu
Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China
Duo Zhang
Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, No. 910, Hengshan Road, Shanghai 200030, China; Shanghai Municipal Key Clinical Specialty, Shanghai, China
Wei Xia
Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, No. 910, Hengshan Road, Shanghai 200030, China; Shanghai Municipal Key Clinical Specialty, Shanghai, China
Yiqin Zhang
Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, No. 910, Hengshan Road, Shanghai 200030, China; Shanghai Municipal Key Clinical Specialty, Shanghai, China
Linlin Jiang
School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
Long Cui
Department of Reproductive Endocrinology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China
Yinghui Ye
Department of Reproductive Endocrinology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China
Yangfei Xiang
School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
Junhao Hu
Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China
Jian Zhang
Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, No. 910, Hengshan Road, Shanghai 200030, China; Shanghai Municipal Key Clinical Specialty, Shanghai, China; Corresponding author
Chao-Po Lin
School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Corresponding author
Summary: 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.
