作者
Qingqing Zhang,Cheuk‐Lun Lee,Tingyu Yang,Jianlin Li,Qunxiong Zeng,Xiaofeng Liu,Z.X. Liu,Degong Ruan,Zhuoxuan Li,Anita Sik Yau Kan,Ka Wang Cheung,A. Mak,Vivian Wai Yan Ng,Huashan Zhao,Xiujun Fan,Yonggang Duan,Liuying Zhong,Min Chen,Meirong Du,Raymond Li,Pentao Liu,Ernest Hung Yu Ng,William S.B. Yeung,Ya Gao,Yao Yuan-qing,Philip C.N. Chiu
摘要
Early-onset preeclampsia (EOPE) is a severe pregnancy complication associated with defective trophoblast differentiation and functions at implantation, but manifestation of its phenotypes is in late pregnancy. There is no reliable method for early prediction and treatment of EOPE. Adrenomedullin (ADM) is an abundant placental peptide in early pregnancy. Integrated single-cell sequencing and spatial transcriptomics confirm a high ADM expression in the human villous cytotrophoblast and syncytiotrophoblast. The levels of ADM in chorionic villi and serum were lower in first-trimester pregnant women who later developed EOPE than those with normotensive pregnancy. ADM stimulates differentiation of trophoblast stem cells and trophoblast organoids in vitro. In pregnant mice, placenta-specific ADM suppression led to EOPE-like phenotypes. The EOPE-like phenotypes in a mouse PE model were reduced by a placenta-specific nanoparticle-based forced expression of ADM. Our study reveals the roles of trophoblastic ADM in placental development, EOPE pathogenesis, and its potential clinical uses.