Targeting the syncytiotrophoblast: A central player in the pathogenesis and therapy of preeclampsia

Preeclampsia (PE) is a severe pregnancy-specific disorder and a leading cause of maternal and perinatal morbidity and mortality. Its complex pathogenesis and the lack of effective therapies beyond delivery represent a major unmet clinical need. The syncytiotrophoblast (STB), the multinucleated cell layer at the outermost layer of the placental villous structure formed by the fusion of villous cytotrophoblasts (VCTs), serve as a critical functional barrier and regulatory hub at the maternal-fetal interface. Recent research highlights the central role of STB in the development of PE. This review delineates the multifaceted dysfunction of STB in PE, including impairments in differentiation, secretion, metabolism, cell survival and cellular heterogeneity. We further evaluate the utility of current experimental models for investigating STB pathobiology and highlight cutting-edge strategies for PE prediction and therapy that target STB. By integrating these insights, this review underscores that a deep understanding of STB biology is pivotal for developing novel diagnostic, predictive and therapeutic solutions to combat PE.