Progress of GDF-15 in preeclampsia: a review

Preeclampsia is a multisystem hypertensive disorder of pregnancy that significantly increases maternal and fetal morbidity and long‑term cardiovascular risk. Growth differentiation factor 15 (GDF‑15) is a stress‑responsive member of the TGF‑β superfamily that is highly expressed in the placenta and secreted into the maternal circulation, where levels rise markedly during gestation. Emerging evidence has positioned GDF‑15 as a potential biomarker for preeclampsia, with multiple studies reporting elevated concentrations in affected women, particularly in early‑onset disease. This review comprehensively examines the molecular mechanisms governing GDF‑15 generation, maturation, and secretion, and delineates its functional roles in placental physiology, including trophoblast invasion, syncytiotrophoblast renewal, endothelial protection, and metabolic regulation. We further explore the genetic architecture of the GDF15 locus, highlighting functional variants such as rs888663 that influence expression levels and may modulate disease susceptibility. The clinical utility of GDF‑15 is critically appraised in the context of established angiogenic markers, with emphasis on its additive predictive value, temporal limitations relative to the aspirin preventive window, and the need for assay standardization. Finally, key unresolved questions are identified, including whether GDF‑15 elevation is pathogenic or compensatory, and how it interacts with the broader network of angiogenic, inflammatory, and metabolic pathways in preeclampsia.