Proinflammatory and Antiangiogenic Effects of Gingival Crevicular Fluid on Placental and Immune Cells: Implications for Oxidative Stress and NET Formation in Pregnancy

PROBLEM: An association between periodontal disease and adverse pregnancy outcomes, with high risk for the mother and the newborn, has been widely documented. So far, the mechanisms linking gingival inflammation to placental dysfunction remain poorly defined. METHODS OF STUDY: In this study, we aimed to investigate whether bioactive inflammatory components in the gingival crevicular fluid are capable of modulating placental and immune cells in vitro and to analyse whether these effects correlate with periodontal parameters. We conducted a cross-sectional study in 37 pregnant women undergoing caesarean section, evaluating their gingival inflammatory condition and collecting gingival crevicular fluid (GCF) within 24 h of delivery. GCF samples were assayed on placental explants, vascular endothelial cells, and neutrophils in vitro to determine inflammatory and functional profiles. RESULTS: The GCF from pregnant women induced a proinflammatory response in placental tissue and an antiangiogenic effect on endothelial cells. Neutrophils exposed to the GCF samples of pregnant women showed increased production of reactive oxygen species and neutrophil extracellular trap (NET) formation. The extent of the inflammatory response correlated with the degree of the maternal gingival inflammatory condition. CONCLUSION: These findings suggest that components present in the GCF induce inflammatory stress even in normal pregnancies. Their potential contribution to periodontal disease-associated complications requires further studies. The present work highlights the value of integrating oral health into prenatal care and offers new experimental approaches to monitor systemic effects of periodontal disease during pregnancy. TRAIL REGISTRATION: This was an observational human study and was not registered in a public clinical trial/study registry.