P. gingivalis/F. nucleatum in Chronic Apical Periodontitis are Associated with Gestational Shortening via the TLR4/MyD88/NF-κB Pathway.

Spontaneous preterm birth (sPTB; delivery before 37 weeks) remains a leading cause of neonatal mortality, and intrauterine infection is implicated in a substantial proportion of cases. Emerging evidence links oral pathogens such as Porphyromonas gingivalis and Fusobacterium nucleatum to adverse gestational outcomes; however, the mechanistic pathways connecting chronic apical periodontitis (CAP) with gestational risk remain incompletely defined. In pregnant C57BL/6J mice, CAP was established by root canal inoculation and complemented by a tail-vein challenge model using bacterial suspensions (1 × 108 CFU/mL). Gestational length, placental histopathology, inflammatory markers, and bacterial DNA signals were assessed by qPCR. In parallel, human trophoblasts were exposed to P. gingivalis or F. nucleatum (MOI = 50, 24 h) to examine inflammatory signaling consistent with activation of the TLR4/MyD88/NF-κB axis. Relative to controls, CAP-associated groups showed gestational shortening (median 19.5 vs 20.5 days), accompanied by increased placental inflammatory readouts (including elevated IL-1β and TNF-α) and histopathological features consistent with inflammatory injury. qPCR further indicated the presence of bacterial DNA signals in placental and vascular tissues. In trophoblast assays, F. nucleatum elicited stronger proinflammatory responses than P. gingivalis, in association with increased NF-κB phosphorylation. Collectively, these findings suggest that CAP-associated oral pathogens may contribute to gestational shortening by driving placental inflammation via TLR4/MyD88/NF-κB signaling, supporting an oral-placental microbial axis as a potential target for mitigating infection-related gestational risk.