Types of Preeclampsia According to Placental Single Cell RNA Sequencing, Type 1 and Type 2 Levels - Insights and Clinical Implications

INTRODUCTION: Preeclampsia, one of the Great Obstetrical Syndromes, remains a major contributor to maternal and fetal morbidity worldwide. Its clinical heterogeneity, classically reflected in "early" versus "late" presentations, underscores the need for biologically grounded sub-classifications to guide diagnosis and management. OBJECTIVES: To characterize the cellular and molecular mechanisms underlying preeclampsia subtypes using advanced single-cell and single-nuclei transcriptomic approaches, and to evaluate their alignment with a proposed integrated model distinguishing Type I (placental dysfunction) from Type II (maternal cardiovascular maladaptation) preeclampsia. METHODS: We performed single-cell and single-nuclei RNA sequencing on approximately 90,000 placental cells, encompassing 46 distinct cell populations, including trophoblast, lymphoid, myeloid, stromal, and endothelial lineages. Comparative transcriptomic analyses were conducted between early-onset and late-onset preeclampsia and control pregnancies. RESULTS: Profound cellular dysregulation was identified in early-onset preeclampsia across multiple placental cell types, consistent with widespread placental dysfunction, angiogenic imbalance, inflammatory response and apoptosis. In contrast, late-onset preeclampsia exhibited comparatively subtle transcriptional changes, suggestive of a distinct pathophysiological process driven by maternal cardiovascular maladaptation, placental aging, cellular senescence and oxidative stress. These findings support the classification of preeclampsia into Type I (placental-dominant, early-onset) and Type II (maternal-dominant, late-onset) forms, each characterized by specific risk factors, biomarkers, and therapeutic targets. CONCLUSIONS: This placental molecular atlas integrates single-cell and single-nuclei transcriptomic data with clinical phenotypes, providing mechanistic support for the Type I and Type II preeclampsia framework. These insights inform the development of targeted interventions, including RNA-based therapies to modulate placental angiogenic pathways in early-onset disease, and maternal cardiovascular optimization strategies in late-onset disease.