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.

中文翻译：

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牙龈假单胞菌感染的巨噬细胞外囊泡导致不良妊娠结局


牙周炎是一种由口腔细菌感染引发的慢性炎症性疾病，牙龈卟啉单胞菌是主要的病原体。牙周炎与各种全身性疾病之间的关联已得到证实。最近的研究还强调了孕产妇牙周炎恶化与早产和低出生体重等不良妊娠结局之间的关系。然而，牙周炎因素如何影响妊娠和胎儿发育的分子机制仍不清楚。细胞外囊泡 （EV） 是由各种类型的细胞分泌到组织微环境中的纳米级球形颗粒。由于电动汽车在细胞间通讯中的作用，近年来引起了人们的兴趣。在本研究中，我们调查了来自牙龈卟啉单胞菌感染的巨噬细胞 （Pg-inf EV） 的 EV 是否到达胎儿胎盘单位并影响胎儿发育。通过在小鼠身上进行一系列体内实验，我们证明 Pg-inf EV 易位到胎儿胎盘单位并损害胎儿大小和体重的发育。组织学分析显示 Pg-inf EV 注射组的胎盘血管排列定向障碍和血管生成受损，表明胎盘功能受损。蛋白质组分析显示实验组胎盘中 Vegfr1 表达显著降低。此外，Pg-inf EV 降低了培养的人血管内皮细胞中 VEGFR1 的表达，突出了这些 EV 对胎盘血管生成产生影响的潜在分子机制。 这是第一项揭示母体牙周炎中口腔细菌感染的巨噬细胞 EV 通过胎盘单位影响妊娠的新途径的研究。