2. Academic Validation
  3. The role of FAK signaling in early placental development and trophoblast lineage specification in human pregnancy

The role of FAK signaling in early placental development and trophoblast lineage specification in human pregnancy

  • Cell Signal. 2025 Oct:134:111946. doi: 10.1016/j.cellsig.2025.111946.
Hong-Xiu Liang 1,  Cen Yi 1,  Si-Hui He 1,  Li-Yang Zhou 1,  Fang-Fang Li 1,  Jing Tang 1,  En-Xiang Chen 1,  Li-Juan Fu 2,  Ying-Xiong Wang 3,  You-Long Xie 4,  Yu-Bin Ding 5
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, Women and Children's Hospital of Chongqing Medical University, Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, School of Public Health, Chongqing Medical University, Chongqing 401147, China.
  • 2 Department of Obstetrics and Gynecology, Women and Children's Hospital of Chongqing Medical University, Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, School of Public Health, Chongqing Medical University, Chongqing 401147, China; Department of Pharmacology, Academician Workstation, Changsha Medical University, Changsha 410219, China.
  • 3 Department of Obstetrics and Gynecology, Women and Children's Hospital of Chongqing Medical University, Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, School of Public Health, Chongqing Medical University, Chongqing 401147, China. Electronic address: 100115@cqmu.edu.cn.
  • 4 Department of Obstetrics and Gynecology, Women and Children's Hospital of Chongqing Medical University, Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, School of Public Health, Chongqing Medical University, Chongqing 401147, China; Hunan Provincial Key Laboratory of the Traditional Chinese Medicine Agricultural Biogenomics, Changsha Medical University, 410129, China. Electronic address: 191029@cqmu.edu.cn.
  • 5 Department of Obstetrics and Gynecology, Women and Children's Hospital of Chongqing Medical University, Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, School of Public Health, Chongqing Medical University, Chongqing 401147, China. Electronic address: dingyb@cqmu.edu.cn.
PMID: 40553964 DOI: 10.1016/j.cellsig.2025.111946
Abstract

The placenta serves as a vital interface for fetal-maternal exchange, relying on trophoblast differentiation for development. This process involves cytotrophoblasts (CTBs) transitioning into syncytiotrophoblasts (STBs) and extravillous trophoblasts (EVTs), driving placental maturation. Focal adhesion kinase (FAK), a key cytoplasmic tyrosine kinase, regulates cellular processes such as proliferation, survival, and signaling. However, its role in trophoblast differentiation and metabolism remains unclear. Here, using human trophoblast stem cells (hTSCs) and trophoblast cell lines (BeWo, HTR8/SVneo), we investigated FAK signaling in trophoblast lineage differentiation. Inhibiting the FAK signaling pathway suppresses MAPK pathway activity, reduces glycolytic metabolism and impairs trophoblast syncytialization. Additionally, blocking FAK with the inhibitor Defactinib disrupts EVTs Cytoskeleton and impairs migration, invasion, and differentiation potential. Notably, reduced FAK signaling is observed in patients with recurrent spontaneous abortion (RSA), suggesting a role in RSA pathogenesis. Our findings highlight FAK as a pivotal regulator of trophoblast lineage development, linking it to placental function and RSA. This study offers new insights into placental disorders and potential therapeutic targets.

Keywords

FAK signaling pathway; MAPK signaling; Placenta; Trophoblast lineage decisions.

Figures
Products