2. Academic Validation
  3. Unraveling the role of the WIPF1/ACTN4 complex in podosome formation of human placental EVTs: Insights into recurrent spontaneous abortion

Unraveling the role of the WIPF1/ACTN4 complex in podosome formation of human placental EVTs: Insights into recurrent spontaneous abortion

  • Genes Dis. 2025 May 2;12(6):101665. doi: 10.1016/j.gendis.2025.101665.
Cong Li 1 2,  Shengya Wang 1 2,  Jing Tang 3,  Xin Luo 4,  Luxing Ge 1 2,  Youlong Xie 1 2,  Lijuan Fu 1 2 5,  Lingling Ruan 1 2,  Enoch Appiah Adu-Gyamfi 6,  Fangfang Li 1 2,  Yingxiong Wang 1 2,  Hongbo Qi 4,  Yubin Ding 1 2 5
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, Women and Children's Hospital of Chongqing Medical University, Chongqing 401147, China.
  • 2 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.
  • 3 Department of Bioinformatics, School of Basic Medicine, Chongqing Medical University, Chongqing 400016, China.
  • 4 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
  • 5 Department of Pharmacology, Academician Workstation, School of Pharmacology, Changsha Medical University, Changsha, Hunan 410219, China.
  • 6 Department of Biomedical Sciences, State University of New York at Albany, Albany, NY 12222, USA.
PMID: 40821124 DOI: 10.1016/j.gendis.2025.101665
Abstract

Successful placental development and pregnancy rely on effective extravillous trophoblast (EVT) invasion. The mechanisms underlying inadequate EVT invasion in recurrent spontaneous abortion (RSA) remain unclear. WAS/WASL interacting protein family member 1 (WIPF1), the key regulator of cytoskeletal dynamics, is exclusively expressed in first-trimester placental EVTs. Knockdown experiments revealed WIPF1's crucial involvement in successful placental development; reduced levels impaired cell migration, while overexpression induced the opposite effects. Moreover, WIPF1 knockdown in hTSC-derived EVTs hampered trophoblast differentiation. WIPF1 interacted with ACTN4 to regulate podosome formation, matrix degradation, and actin polymerization, potentially mediated by its ARG54 site. Notably, WIPF1 was significantly down-regulated in human RSA patient EVTs and RSA mice trophoblast giant cells (CBA/J × DBA/2). This association suggests WIPF1 as a potential key player in RSA pathogenesis. In conclusion, our study spotlights WIPF1 as a pivotal factor in EVT invasion, emphasizing its multifaceted roles and implications in pregnancy complications like RSA.

Keywords

Extravillous trophoblasts; Invasion; Podosome formation; Recurrentspontaneous abortion; WIPF1.

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