プレエクランプシアにおけるマルチオミクスおよび血清バイオマーカーによって明らかになったサブタイプ特異的な免疫代謝再プログラミング
Yixuan Chen1, Linlin Wu2, Dongni Huang3
1Department of Reproductive Medical Center, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital of Henan University, Zhengzhou, Henan, China.
Abstract:
Preeclampsia comprises early-onset (EOPE) and late-onset (LOPE) subtypes with distinct etiologies, placental pathology, and severity, but cellular/metabolic drivers and early biomarkers remain unclear. We integrated placental single-cell RNA-seq, spatial transcriptomics, and spatial metabolomics from EOPE, LOPE, and matched controls, and performed maternal serum metabolomics in a prospective cohort of 199 pregnancies. The scRNA-seq identified 14 cell types; Hofbauer cells and trophoblasts resolved into 7 and 3 subclusters. EOPE placentas showed increased macrophages and extravillous trophoblasts, reduced oxygen-transporting Hofbauer subtypes (HB_1, HB_6), and trophoblasts with heightened HIF-1, VEGF, and IGF signaling. LOPE preserved cellular composition but exhibited stronger inflammatory transcriptional programs. Spatial analyses indicated disrupted oxygen transport in EOPE and perturbed interferon-γ signaling and exosome secretion in LOPE. Metabolically, trophoblasts and Hofbauer cells displayed subtype-specific lipid-transport defects and mitochondrial dysfunction. Three early-pregnancy serum metabolites-phosphatidylcholine PC(22:5/0:0), 3-hydroxybutyric acid, and L-allothreonine-robustly predicted EOPE (AUC > 0.85). This study delineates preeclampsia as a spectrum of placental immune-metabolic disorders. Hofbauer cells and trophoblasts undergo subtype-specific transcriptional and metabolic remodeling in EOPE vs LOPE. Multi-omics-guided, noninvasive biomarkers enable early EOPE risk prediction, informing timely detection and intervention.
