To address this, the current study utilized a comprehensive approach, including chromatin immunoprecipitation sequencing (ChIP-seq), 4-dimensional label-free quantitative proteomics integrated with lactylation analysis (4D-LFQP-LA), and a Mini patient-derived xenograft (MiniPDX) model, to explore the regulatory mechanisms through which reduced HLA-F expression inhibits trophoblast proliferation and glycolysis, ultimately contributing to the pathogenesis of preeclampsia. This evidence concerns the gene HLA-F and preeclampsia.