P. gingivalis/F. nucleatum in Chronic Apical Periodontitis are Associated with Gestational Shortening via the TLR4/MyD88/NF-&#954;B Pathway

Yangyang Zhang; Xiaohe Wang; Meng Li; Zeyu Wu; Jing Lin; Xianmei Yu; Ling Li; Jin Zhao

doi:10.3791/70793

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Research Article

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

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DOI:

10.3791/70793

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May 15th, 2026

Yangyang Zhang¹^,²^,³ , Xiaohe Wang¹^,³ , Meng Li⁴ , Zeyu Wu¹^,³ , Jing Lin¹^,³ , Xianmei Yu¹^,³ , Ling Li⁵ , Jin Zhao¹^,³

¹Department of Cariology and Endodontics, The First Affiliated Hospital of Xinjiang Medical University, The Affiliated Stomatology Hospital of Xinjiang Medical University, ²Development and Related Diseases of Women and Children Key Laboratory of Sichuan Province, ³Stomatology Disease Institute of Xinjiang Uyghur Autonomous Region, Xinjiang Medical University, ⁴Department of Endodontics, Urumqi Stomatological Hospital, ⁵Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xinjiang Medical University

Summary

Chronic apical periodontitis–associated oral pathogens (P. gingivalis, F. nucleatum) are evaluated using murine CAP models and human trophoblast infection assays. Gestational shortening is observed alongside placental inflammatory activation consistent with TLR4/MyD88/NF-κB signaling. Bacterial DNA is detectable in placental/vascular tissues, supporting a hematogenous link and potential intervention targets.

Abstract

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.

Introduction

Spontaneous preterm birth (sPTB) is defined as delivery occurring between 20–37 weeks of gestation without medical intervention¹. As a critical global public health concern, the incidence of sPTB ranges from approximately 5%–9% in developed countries to 12%–18% in resource-limited regions²^,³. Preterm birth and its complications remain a leading cause of mortality in children under 5 years of age, accounting for approximately one million neonatal deaths annually⁴. Survivors often experience both immediate complications, such as respiratory distre....