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

doi:10.1016/j.celrep.2023.112546

Modeling human ectopic pregnancies with trophoblast and vascular organoids

Cell Rep. 2023 Jun 27;42(6):112546. doi: 10.1016/j.celrep.2023.112546. Epub 2023 May 23.

Authors

Xiaoya Zhao¹, Zhenwu Zhang², Qian Zhu¹, Yurui Luo², Qinying Ye², Shuxiang Shi², Xueyang He³, Jing Zhu³, Duo Zhang¹, Wei Xia¹, Yiqin Zhang¹, Linlin Jiang², Long Cui⁴, Yinghui Ye⁴, Yangfei Xiang², Junhao Hu³, Jian Zhang⁵, Chao-Po Lin⁶

Affiliations

¹ 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.
² School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
³ Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China.
⁴ Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China.
⁵ 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. Electronic address: zhangjian_ipmch@sjtu.edu.cn.
⁶ School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China. Electronic address: linzhb@shanghaitech.edu.cn.

PMID: 37224015
DOI: 10.1016/j.celrep.2023.112546

Abstract

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.

Keywords: CP: Stem cell research; WNT signaling; angiogenesis; ectopic pregnancy; trophoblast organoid; vascular organoid.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Embryo Implantation
Female
Humans
Organoids
Placenta / pathology
Pregnancy
Pregnancy, Ectopic* / pathology
Trophoblasts*