<i>Porphyromonas gingivalis</i>and adverse pregnancy outcome

Reyes, Leticia; Phillips, Paul; Wolfe, Bryce; Golos, Thaddeus G.; Walkenhorst, Molly; Progulske‐Fox, Ann; Brown, Mary Bomberger

doi:10.1080/20002297.2017.1374153

Cited by 38 publications

(37 citation statements)

References 113 publications

(187 reference statements)

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“…Given that bacteria including Pg can be found in the decidua/basal plate [15-17, 22, 25, 56], and that Pg, in particular, is implicated in adverse pregnancy outcomes [57], we wanted to determine if Pg could promote DDP. Using a rat model of infection, we were able to establish that Pg reaches the maternal-fetal interface and induces lesions consistent with DDP including increased fetal loss, albeit in a microbial strain-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Porphyromonas gingivalis strain-dependent inhibition of uterine spiral artery remodeling in the pregnant rat†

Phillips

Brown

Progulske‐Fox

et al. 2018

Biology of Reproduction

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Porphyromonas gingivalis (Pg) is an important periodontal pathogen that is also implicated in pregnancy complications involving defective deep placentation (DDP). We hypothesized that Pg invasion of the placental bed promotes DDP. Pregnant rats were intravenously inoculated with sterile vehicle, Pg strain W83, or A7436 at gestation day (GD) 14 (acute cohort). Nonpregnant rats received repeated oral inoculations for 3 months before breeding (chronic cohort). Tissues and/or sera were collected at GD18 for analysis. Pg infection status was determined by seroconversion (chronic cohort) and by presence of Pg antigen in utero-placental tissues processed for histology and morphometric assessment of spiral artery remodeling. Mesometrial tissues from seropositive dams were analyzed for expression of interleukin 1β, 6, and 10, TNF, TGF-β, follistatin-related protein 3, and inhibin beta A chain since these genes regulate extravillous trophoblast invasion. The in situ distribution of W83 and A7436 antigen in utero-placental tissues was similar in both cohorts. In the acute cohort, mesometrial stromal necrosis was more common with W83, but arteritis was more common with A7436 infection (P < 0.05). Increased vascular necrosis was seen in mesometrium of chronically infected groups (P < 0.05). Only A7436-infected animals had increased fetal deaths, reduced spiral artery remodeling, reduced inhibin beta A expression, and an increased proportion of FSLT3 positive extravillous trophoblasts within spiral arteries. While infection with both Pg strains produced varying pathology of the deep placental bed, only infection with strain A7436 resulted in impaired spiral artery remodeling.Published by Oxford University Press on behalf of Society for the Study of Reproduction 2018. This work is written by (a) US Government employee(s) and is in the public domain in the US. 1045Downloaded from https://academic.oup.com/biolreprod/article-abstract/99/5/1045/4999895 by guest on 07 June 2019 1046 P. Phillips et al., 2018, Vol. 99, No. 5 Summary SentenceInvasion of the placental bed by Porphyromonas gingivalis impairs spiral artery remodeling and increases fetal loss in a microbial strain-dependent manner.

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Section: Discussionmentioning

confidence: 99%

Porphyromonas gingivalis strain-dependent inhibition of uterine spiral artery remodeling in the pregnant rat†

Phillips

Brown

Progulske‐Fox

et al. 2018

Biology of Reproduction

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“…P. gingivalis has been associated with adverse pregnancy outcomes (APOs) [64,65]. A hemin-rich medium promotes the growth of TLR4 antagonist forms of P. gingivalis [25].…”

Section: Dysregulation Of the Tlr Function May Cause Adverse Pregnancmentioning

confidence: 99%

“…This may have consequences for the placenta, which is a blood-rich tissue with abundance of red blood cells. The placental environment may, therefore, be rich in tetra- and penta-acylated residues in the A-LPS of P. gingivalis [64]. The ability of P. gingivalis to generate two different isoforms of A-LPS that either activate or antagonize TLR4 could be particularly important to the maternal–foetal interface [64].…”

Section: Dysregulation Of the Tlr Function May Cause Adverse Pregnancmentioning

confidence: 99%

“…The placental environment may, therefore, be rich in tetra- and penta-acylated residues in the A-LPS of P. gingivalis [64]. The ability of P. gingivalis to generate two different isoforms of A-LPS that either activate or antagonize TLR4 could be particularly important to the maternal–foetal interface [64]. P. gingivalis dysregulation of the TLR function in uterus, placenta, and foetal membranes may promote APO [64–67].…”

Section: Dysregulation Of the Tlr Function May Cause Adverse Pregnancmentioning

confidence: 99%

“…The ability of P. gingivalis to generate two different isoforms of A-LPS that either activate or antagonize TLR4 could be particularly important to the maternal–foetal interface [64]. P. gingivalis dysregulation of the TLR function in uterus, placenta, and foetal membranes may promote APO [64–67]. In rats, LPS from P. gingivalis increased maternal blood pressure, induced placental and foetal growth restriction, and increased foetal resorptions, without inducing proteinuria and inflammation [68].…”

Section: Dysregulation Of the Tlr Function May Cause Adverse Pregnancmentioning

confidence: 99%

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Importance of heterogeneity in Porhyromonas gingivalis lipopolysaccharide lipid A in tissue specific inflammatory signalling

Olsen

Singhrao

2018

Journal of Oral Microbiology

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Lipopolysaccharide (LPS) of Porphyromonas gingivalis exists in at least two known forms, O-LPS and A-LPS. A-LPS shows heterogeneity in which two isoforms designated LPS1,435/1,449 and LPS1,690 appear responsible for tissue-specific immune signalling pathways activation and increased virulence. The modification of lipid A to tetra-acylated1,435/1,449 and/or penta-acylated1,690 fatty acids indicates poor growth conditions and bioavailability of hemin. Hemin protects P. gingivalis from serum resistance and the lipid A serves as a site for its binding. The LPS1,435/1,449 and LPS1,690 isoforms can produce opposite effects on the human Toll-like receptors (TLR) TLR2 and TLR4 activation. This enables P. gingivalis to select the conditions for its entry, survival, and that of its co-habiting species in the host, orchestrating its virulence to control innate immune pathway activation and biofilm dysbiosis. This review describes a number of effects that LPS1,435/1,449 and LPS1,690 can exert on the host tissues such as deregulation of the innate immune system, subversion of host cell autophagy, regulation of outer membrane vesicle production, and adverse effects on pregnancy outcome. The ability to change its LPS1,435/1,449 and/or LPS1,690 composition may enable P. gingivalis to paralyze local pro-inflammatory cytokine production, thereby gaining access to its primary location in periodontal tissue.

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Porphyromonas gingivalis outer membrane vesicles shape trophoblast cell metabolism impairing functions associated to adverse pregnancy outcome

Lara,

Loureiro,

Gliosca

et al. 2023

Journal Cellular Physiology

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Periodontitis is proposed as a risk factor for preterm delivery, fetal growth restriction, and preeclampsia with severe consequences for maternal and neonatal health, but the biological mechanisms involved are elusive. Porphyromonas gingivalis gain access to the placental bed and impair trophoblast cell function, as assessed in murine and human pregnancy, suggesting a pathogenic role in adverse pregnancy and neonatal outcomes. P. gingivalis releases outer membrane vesicles (P. gingivalis OMV) during growth that spread to distant tissues and are internalized in host cells as described in metabolic, neurological, and vascular systemic diseases. Here we tested the hypothesis that P. gingivalis OMV internalized in trophoblast cells disrupt their metabolism leading to trophoblast and placenta dysfunction and adverse pregnancy outcomes. An in vitro design with human trophoblast cells incubated with P. gingivalis OMV was used together with ex vivo and in vivo approaches in pregnant mice treated with P. gingivalis OMV. P. gingivalis OMV modulated human trophoblast cell metabolism by reducing glycolytic pathways and decreasing total reactive oxygen species with sustained mitochondrial activity. Metabolic changes induced by P. gingivalis OMV did not compromise cell viability; instead, it turned trophoblast cells into a metabolic resting state where central functions such as migration and invasion were reduced. The effects of P. gingivalis OMV on human trophoblast cells were corroborated ex vivo in mouse whole placenta and in vivo in pregnant mice: P. gingivalis OMV reduced glycolytic pathways in the placenta and led to lower placental and fetal weight gain in vivo with reduced placental expression of the glucose transporter GLUT1. The present results point to OMV as a key component of P. gingivalis involved in adverse pregnancy outcomes, and even more, unveil a metabolic cue in the deleterious effect of P. gingivalis OMV on trophoblast cells and mouse pregnancy, providing new clues to understand pathogenic mechanisms in pregnancy complications and other systemic diseases.

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Porphyromonas gingivalisand adverse pregnancy outcome

Cited by 38 publications

References 113 publications

Porphyromonas gingivalis strain-dependent inhibition of uterine spiral artery remodeling in the pregnant rat†

Porphyromonas gingivalis strain-dependent inhibition of uterine spiral artery remodeling in the pregnant rat†

Importance of heterogeneity in Porhyromonas gingivalis lipopolysaccharide lipid A in tissue specific inflammatory signalling

Porphyromonas gingivalis outer membrane vesicles shape trophoblast cell metabolism impairing functions associated to adverse pregnancy outcome

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