Periodontal infection with Porphyromonas gingivalis induces preterm birth and lower birth weight in rats

Abstract

Preterm birth (PTB), accompanied by low birth weight (LBW) or not, is a syndrome with tremendous risk factors and long-term health consequences for children. In recent decades, overwhelming studies have shown that periodontitis contributes to prematurity and LBW. This study was conducted to determine the link between maternal periodontitis and the pathogenesis of PTB and/or LBW through a rat infection model induced by Porphyromonas gingivalis, an important periodontopathic bacterium. The murine model was established by surgically ligating the left mandibular first molars and inoculating with P. gingivalis, and then all female rats initiated mating 6 weeks post infection. The gestational day and birth weight were recorded, and blood, amniotic fluid, and placental specimens were collected. Rats with a PTB and LBW newborns were observed in the P. gingivalis-infected group. Additionally, P. gingivalis infection significantly increased the maternal serum levels of interferon-γ and interleukin-1β, whereas no significant difference in the cytokine response was observed in the amniotic fluid. Moreover, with the translocation of P. gingivalis to placentas, remarkable changes in gestational tissues were found, followed by significantly enhanced expression of Toll-like receptor 2 (TLR2) as well as Fas and Fas ligand (FasL). These results support the concept that severe cases of periodontitis caused by P. gingivalis infection may be indicative of rats being more susceptible to PTB/LBW, probably through the activation of the TLR2 and Fas/FasL pathways within the placental tissues. This study gave us new insight into how maternal periodontopathogens might be linked to placental damage and premature pathogenesis.

Fetal growth restriction is a host specific response to infection with an impaired spiral artery remodeling-inducing strain of Porphyromonas gingivalis

“…Herein we report that P. gingivalis infection induced ISAR in both rat strains, but only infected WIS dams exhibited FGR. In contrast to other studies 10,15 , neither maternal systemic inflammation nor placental (fetal) inflammation was a feature of FGR. In addition, placental microbial load was equivalent in both rat strains suggesting this was not a determining factor in the development of FGR.…”

“…Using a rodent model of infection, we previously demonstrated that P. gingivalis disrupts the physiologic remodeling of the uterine spiral arteries during pregnancy 11 , providing a common mechanistic model for how this microbe could contribute to a wide array of pregnancy disorders. One unexpected outcome from that study was the lack of FGR with P. gingivalis infection 11 even though FGR can be an outcome of infection 10,[13][14][15]45 as well as a complication of ISAR 34 . Given that different rat strains show varying susceptibility to infection and injury [46][47][48] , we originally postulated that P. gingivalis-induced FGR was a rat strain dependent phenomenon.…”

“…We profiled serum cytokine/chemokine levels in SD and WIS dams since experimental infection with P. gingivalis has been shown to increase maternal pro-inflammatory responses 10,13,15 . Neither TNF-α, GM-CSF, IL-12p70, nor IL-1α were detected in either rat strain (data not shown).…”

Porphyromonas gingivalis and Its Systemic Impact: Current Status

“…These results suggest the involvement of P. gingivalis in APOs through direct invasion and damage to utero-placental tissues. Subsequently, various rodent models confirmed that P. gingivalis infection can induce diverse utero-placental pathologies (such as endometrial arteritis, mild chorioamnionitis, and utero-placental hemorrhage with structural disorder of placenta) and cause a diverse array of APOs, including fetal growth restriction (FGR), low birth weight (LBW), and PB [ 137 , 138 , 139 ].…”

“…The direct dissemination of P. gingivalis to the placenta and its pathogenicity mechanisms have been proposed in many animal experiments. It has been reported that P. gingivalis could translocate to local placental tissues in rats and enhance the expression of Fas, FasL, and TLR2, leading to PB and LBW [ 137 ]. P. gingivalis infection in pregnant mice induced a fetus-specific placental immune response and increased the placental Th1/Th2 cytokine ratio (increased expression of IFN-γ, IL-2, and IL-12, decreased expression of IL-4 and IL-10), which may be related to the occurrence of FGR [ 138 ].…”