Dynamic changes in neutrophil activation and metabolic profile during pregnancy are associated with gingival inflammation

CALO, GUILLERMINA; MERECH, FÁTIMA; SABBIONE, FLORENCIA; D?ERAMO, LUCIANA; DOGA, LUCIANA; LARA, BRENDA; HAUK, VANESA; GLIOSCA, LAURA; NOVOA, SOFÍA; SANTILLÁN, ARIANA; FABIANO, PABLO; RAMHORST, ROSANNA; SQUASSI, ALDO; VOTA, DAIANA; LEIRÓS, CLAUDIA PÉREZ

Scientific Reports

Nature

Año: 2025 vol. 15

Neutrophils are key players in both periodontal and placental immunity, undergoing profoundimmunometabolic and functional changes during pregnancy. Their excessive activation has been linkedto gestational complications. Gingivitis, and even more so periodontitis, the advanced stage of thiscondition, are chronic inflammatory diseases that frequently worsen during pregnancy and have beenassociated with adverse outcomes such as fetal growth restriction and placental dysfunction. Althoughbacterial dissemination and inflammation are thought to mediate this link, the underlying mechanismsremain poorly understood. How neutrophil activation and metabolism evolve throughout pregnancy—and how this relates to the exacerbation of periodontal inflammation—remains largely unexplored.We analyzed the immunometabolic and activation profiles of circulating neutrophils from pregnantwomen at 16–20 weeks and term, alongside their gingival inflammatory status. Our findings showthat pregnancy reprograms neutrophil metabolism, promoting a progressive shift towards enhancedglucose utilization and increased lipid droplet accumulation at term. Basal reactive oxygen speciesproduction increased throughout pregnancy and correlated with gingival inflammation. Basal andPMA-induced neutrophil extracellular trap release also increased with gestation. Gingival crevicularfluid samples further stimulated neutrophil activation, particularly those enriched in P. gingivalis. Theseresults reveal a dynamic immunometabolic rewiring in maternal circulating neutrophils throughoutpregnancy, suggesting its modulatory role in the interplay between systemic immunity and oralinflammation.