Dysregulation of MYBL2 impairs extravillous trophoblast lineage development and function, contributing to recurrent spontaneous abortion

• 成果类型: Article
• 署名作者: Wu, Zhi-Hong; Yi, Cen; Chen, En-Xiang; Xu, Jia-Qi; Li, Cong; Yao, Lu; Li, Fang-Fang; Fu, Li-Juan; Ge, Lu-Xing; Wang, Ying-Xiong; Xie, You-Long; Ding, Yu-Bin; Tang, Jing
• 署名单位: Chongqing Medical University; Chongqing Medical University; Chongqing Medical University; Changsha Medical University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12708
• DOI: 10.1073/pnas.2421653122
• 发表日期: 2025-04-28
• 关键词: pregnancy loss; proliferation; pathogenesis; expression; invasion; cells

摘要

Recurrent spontaneous abortion (RSA) is a pregnancy- related condition characterized by a complex etiology. While placental trophoblast dysfunction is strongly associated with the development and progression of RSA, the underlying molecular mechanisms remain poorly understood. In this study, we observed a significant decrease in the expression and the placentas of abortion- prone (AP) mice. Utilizing human trophoblast stem cells (hTSCs), we identified MYBL2 as a critical regulator of hTSCs stemness maintenance, promoting the expression of the stemness- associated genes Tumor protein p63 (TP63) and TEA Domain Transcription Factor 4 (TEAD4). Furthermore, MYBL2 facilitates the differentiation of hTSCs into extravillous trophoblast (EVT) by positively regulating EVT- like model, we found that MYBL2 positively regulates AJUBA expression by binding to the distal region of the AJUBA promoter. Additionally, the MYBL2-AJUBA axis enhances the migration and invasion of HTR- 8/SVneo cells by suppressing the Hippo signaling pathway. Our study indicates that the dysregulation of MYBL2 expression in placental trophoblasts is associated with the pathogenesis of RSA, highlighting its potential as a therapeutic target for this condition.