Enhanced Expression of Contractile-Associated Proteins and Ion Channels in Preterm Delivery Model Mice With Chronic Odontogenic Porphyromonas Gingivalis Infection

Abstract

Inflammation and infection have been reported to induce preterm delivery. We have studied the relationship between inflammation and various ion channels, including the L-type Ca(2+) channel and P2X7 receptor, during acute inflammation of the pregnant rat uterus induced by lipopolysaccharides. Recently, we found that mice with odontogenic Porphyromonas gingivalis (P.g, an important odontogenic pathogen) infection delivered at day 18.3 of gestation (vs. day 20.5 in normal mice). The purpose of this study was to investigate the expression of myometrial contractile-associated proteins inducing contractions and confirm that these mice are useful as a model for preterm delivery induced by chronic inflammation. We examined the expression of the oxytocin receptor, connexin 43, prostaglandin F receptors, L-type Ca(2+) channel, and P2X7 receptor in the myometrium at day 18 of gestation by real-time PCR and western blot analyses. We also measured TNF-α and IL-1β levels in the blood serum, placenta, fetal membrane and myometrium on the same day. mRNA expression of the oxytocin receptor, connexin 43, prostaglandin F receptors, L-type Ca(2+) channel, and P2X7 receptor was elevated by 5.4, 3.2, 2.4, 2.5, and 1.7 fold, respectively, in the P.g-infected mice. Protein levels of the oxytocin receptor and connexin 43 also increased. Serum levels of TNF-α and IL-1β were elevated, showing that systemic inflammation continued during pregnancy. IL-1β levels in the placenta and fetal membrane also increased, suggesting inflammatory reactions were induced. Thus, mice with odontogenic infection may be useful as a model of chronic inflammation-induced preterm delivery.

Porphyromonas gingivalisand adverse pregnancy outcome

“…Intrauterine lesions associated with this outcome consist of necrosis of the decidua, chorionic plate (fetal side of the placenta), and fetal membranes with moderate infiltration of neutrophils and macrophages into the tissue [106]. Subsequent studies with this animal model showed that fetal membranes expressed higher levels of TNF-α and IL-1β than uninfected controls [107], which would be consistent with spontaneous preterm birth initiated by chorioamnionitis [15]. Although less frequent, FGR is also observed in rodents experimentally infected with W83 [106,108], suggesting that some APOs may be common among most P. gingivalis strains.…”

“…Unlike A7436, W83 is more likely to induce spontaneous preterm delivery, at least in mice [106,107]. In this model, periodontal disease is initiated before breeding by inoculating W83 into molar pulp chambers, which produces increased maternal serum levels of TNF-α, IL-17, IL-6, and IL-1β and spontaneous preterm delivery [106].…”

Role of Maternal Periodontitis in Preterm Birth

“…In another study ( 75 ), mice with periodontitis induced by using an inoculum of P. gingivalis and F. nucleatum exhibited increased circulating levels of IL-6 and IL-8. Similarly, Miyoshi et al ( 76 ) found high levels of contractile-associated proteins and ion channels in the myometrium of PTB model mice with chronic odontogenic P. gingivalis infection. In murine models, F. nucleatum translocated and caused intrauterine infections ( 77 ) and Campylobacter rectus significantly decreased fetoplacental weight ( 78 ).…”

Interferon‐Gamma and Fas Are Involved in Porphyromonas gingivalis–Induced Apoptosis of Human Extravillous Trophoblast‐Derived HTR8/SVneo Cells via Extracellular Signal‐Regulated Kinase 1/2 Pathway

“…A number of studies recently revealed a link between periodontal disease and PTB 12 , 13 . Dental infection of Pg induces PTB 20 , 21 . However, molecular mechanisms underlying Pg ‐induced PTB are not yet fully understood.…”

“…Defects in placental tissues of Pg ‐infected mice include: 1) premature rupture of membranes; 2) placental detachment; and 3) degenerative changes in trophoblasts 20 . Dental infection with Pg induces PTB in mice 20 , 21 . An in vitro study showed Pg infection can induce apoptosis in placental trophoblasts through pathways involving extracellular signal‐regulated kinase (ERK) 1/2 22 .…”