RRC ID 85792
著者 Tanai A, Fukuhara Y, Eguchi T, Kawai H, Ueda K, Ochiai K, Ikegame M, Okamoto K, Okamura H.
タイトル P. gingivalis-Infected Macrophage Extracellular Vesicles Cause Adverse Pregnancy Outcomes.
ジャーナル J Dent Res
Abstract Periodontitis is a chronic inflammatory disease triggered by oral bacterial infection, with the bacterium Porphyromonas gingivalis being a major causative agent. The association between periodontitis and various systemic diseases has been demonstrated. Recent research has also highlighted the relationship between the aggravation of maternal periodontitis and adverse pregnancy outcomes such as preterm birth and low birth weight. However, the molecular mechanisms underlying how factors from periodontitis influence pregnancy and fetal development remain unclear. Extracellular vesicles (EVs) are nano-sized spherical particles secreted into the tissue microenvironment by various types of cells. EVs have garnered interest in recent years due to their role in intercellular communication. In the present study, we investigated whether EVs derived from P. gingivalis-infected macrophages (Pg-inf EVs) reach the feto-placental unit and influence fetal development. Through a series of in vivo experiments in mice, we demonstrated that Pg-inf EVs translocated to the feto-placental unit and impaired fetal development in size and weight. Histological analysis revealed disoriented blood vessel alignment and impaired angiogenesis in the placentas of Pg-inf EV-injected groups, indicative of compromised placental function. Proteome analysis revealed a significant decrease in Vegfr1 expression in the placentas of the experimental group. Moreover, Pg-inf EVs reduced VEGFR1 expression in cultured human vascular endothelial cells, highlighting a potential molecular mechanism through which these EVs exert their effects on placental angiogenesis. This is the first study to reveal a novel pathway in which oral bacteria-infected macrophage EVs in maternal periodontitis affect pregnancy via the feto-placental unit.
巻・号 104(1)
ページ 54-63
公開日 2025-1-1
DOI 10.1177/00220345241285132
PMID 39651617
PMC PMC11667200
MeSH Animals Bacteroidaceae Infections / complications Bacteroidaceae Infections / microbiology Extracellular Vesicles* Female Fetal Development Humans Macrophages* / microbiology Mice Mice, Inbred C57BL Periodontitis / microbiology Placenta* / microbiology Porphyromonas gingivalis* Pregnancy Pregnancy Outcome* Premature Birth / microbiology Vascular Endothelial Growth Factor Receptor-1 / metabolism
IF 4.914
リソース情報
ヒト・動物細胞 Human umbilical vascular endothelial cells