Increased TLR4 Expression in Murine Placentas after Oral Infection with Periodontal Pathogens

Roger Mauricio Arce Munoz, S. P. Barros, B. Wacker, B. Peters, K. Moss, S. Offenbacher

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Maternal periodontitis has emerged as a putative risk factor for preterm births in humans. The periodontitis-associated dental biofilm is thought to serve as an important source of oral bacteria and related virulence factors that hematogenously disseminate and affect the fetoplacental unit; however the underlying biological mechanisms are yet to be fully elucidated. This study hypothesized that an oral infection with the human periodontal pathogens Campylobacter rectus and Porphyromonas gingivalis is able to induce fetal growth restriction, placental inflammation and enhance Toll-like receptors type 4 (TLR4) expression in a murine pregnancy model. Female Balb/C mice (n = 40) were orally infected with C. rectus and/or P. gingivalis over a 16-week period and mated once/week. Pregnant mice were sacrificed at embryonic day (E) 16.5 and placentas were collected and analyzed for TLR4 mRNA levels and qualitative protein expression by real-time PCR and immunofluorescence. TLR4 mRNA expression was found to be increased in the C. rectus-infected group (1.98 ± 0.886-fold difference, P < 0.01, ANOVA) compared to controls. Microscopic analysis of murine placentas showed enhanced immunofluorescence of TLR4 in trophoblasts, mainly in the placental labyrinth layer. Also, combined oral infection with C. rectus and P. gingivalis significantly reduced the overall fecundity compared to controls (16.7% vs. 75%, infected vs. non-infected mice respectively, P = 0.03, Kaplan-Meier). The results supported an enhanced placental TLR4 expression after oral infection with periodontal pathogens. The TLR4 pathway has been implicated in the pathogenesis of preterm births; therefore the abnormal regulation of placental TLR4 may give new insights into how maternal periodontitis and periodontal pathogens might be linked to placental inflammation and preterm birth pathogenesis.

Original languageEnglish (US)
Pages (from-to)156-162
Number of pages7
JournalPlacenta
Volume30
Issue number2
DOIs
StatePublished - Feb 1 2009

Fingerprint

Toll-Like Receptor 4
Placenta
Campylobacter rectus
Infection
Periodontitis
Premature Birth
Porphyromonas gingivalis
Fluorescent Antibody Technique
Mothers
Inflammation
Messenger RNA
Trophoblasts
Virulence Factors
Inner Ear
Biofilms
Fetal Development
Fertility
Real-Time Polymerase Chain Reaction
Analysis of Variance
Tooth

Keywords

  • Campylobacter rectus
  • Mice
  • Periodontitis
  • Placenta
  • Porphyromonas gingivalis
  • Preterm birth
  • Toll-like receptors

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology
  • Developmental Biology

Cite this

Increased TLR4 Expression in Murine Placentas after Oral Infection with Periodontal Pathogens. / Arce Munoz, Roger Mauricio; Barros, S. P.; Wacker, B.; Peters, B.; Moss, K.; Offenbacher, S.

In: Placenta, Vol. 30, No. 2, 01.02.2009, p. 156-162.

Research output: Contribution to journalArticle

Arce Munoz, Roger Mauricio ; Barros, S. P. ; Wacker, B. ; Peters, B. ; Moss, K. ; Offenbacher, S. / Increased TLR4 Expression in Murine Placentas after Oral Infection with Periodontal Pathogens. In: Placenta. 2009 ; Vol. 30, No. 2. pp. 156-162.
@article{80c929e859064141af45e80ace810872,
title = "Increased TLR4 Expression in Murine Placentas after Oral Infection with Periodontal Pathogens",
abstract = "Maternal periodontitis has emerged as a putative risk factor for preterm births in humans. The periodontitis-associated dental biofilm is thought to serve as an important source of oral bacteria and related virulence factors that hematogenously disseminate and affect the fetoplacental unit; however the underlying biological mechanisms are yet to be fully elucidated. This study hypothesized that an oral infection with the human periodontal pathogens Campylobacter rectus and Porphyromonas gingivalis is able to induce fetal growth restriction, placental inflammation and enhance Toll-like receptors type 4 (TLR4) expression in a murine pregnancy model. Female Balb/C mice (n = 40) were orally infected with C. rectus and/or P. gingivalis over a 16-week period and mated once/week. Pregnant mice were sacrificed at embryonic day (E) 16.5 and placentas were collected and analyzed for TLR4 mRNA levels and qualitative protein expression by real-time PCR and immunofluorescence. TLR4 mRNA expression was found to be increased in the C. rectus-infected group (1.98 ± 0.886-fold difference, P < 0.01, ANOVA) compared to controls. Microscopic analysis of murine placentas showed enhanced immunofluorescence of TLR4 in trophoblasts, mainly in the placental labyrinth layer. Also, combined oral infection with C. rectus and P. gingivalis significantly reduced the overall fecundity compared to controls (16.7{\%} vs. 75{\%}, infected vs. non-infected mice respectively, P = 0.03, Kaplan-Meier). The results supported an enhanced placental TLR4 expression after oral infection with periodontal pathogens. The TLR4 pathway has been implicated in the pathogenesis of preterm births; therefore the abnormal regulation of placental TLR4 may give new insights into how maternal periodontitis and periodontal pathogens might be linked to placental inflammation and preterm birth pathogenesis.",
keywords = "Campylobacter rectus, Mice, Periodontitis, Placenta, Porphyromonas gingivalis, Preterm birth, Toll-like receptors",
author = "{Arce Munoz}, {Roger Mauricio} and Barros, {S. P.} and B. Wacker and B. Peters and K. Moss and S. Offenbacher",
year = "2009",
month = "2",
day = "1",
doi = "10.1016/j.placenta.2008.11.017",
language = "English (US)",
volume = "30",
pages = "156--162",
journal = "Placenta",
issn = "0143-4004",
publisher = "W.B. Saunders Ltd",
number = "2",

}

TY - JOUR

T1 - Increased TLR4 Expression in Murine Placentas after Oral Infection with Periodontal Pathogens

AU - Arce Munoz, Roger Mauricio

AU - Barros, S. P.

AU - Wacker, B.

AU - Peters, B.

AU - Moss, K.

AU - Offenbacher, S.

PY - 2009/2/1

Y1 - 2009/2/1

N2 - Maternal periodontitis has emerged as a putative risk factor for preterm births in humans. The periodontitis-associated dental biofilm is thought to serve as an important source of oral bacteria and related virulence factors that hematogenously disseminate and affect the fetoplacental unit; however the underlying biological mechanisms are yet to be fully elucidated. This study hypothesized that an oral infection with the human periodontal pathogens Campylobacter rectus and Porphyromonas gingivalis is able to induce fetal growth restriction, placental inflammation and enhance Toll-like receptors type 4 (TLR4) expression in a murine pregnancy model. Female Balb/C mice (n = 40) were orally infected with C. rectus and/or P. gingivalis over a 16-week period and mated once/week. Pregnant mice were sacrificed at embryonic day (E) 16.5 and placentas were collected and analyzed for TLR4 mRNA levels and qualitative protein expression by real-time PCR and immunofluorescence. TLR4 mRNA expression was found to be increased in the C. rectus-infected group (1.98 ± 0.886-fold difference, P < 0.01, ANOVA) compared to controls. Microscopic analysis of murine placentas showed enhanced immunofluorescence of TLR4 in trophoblasts, mainly in the placental labyrinth layer. Also, combined oral infection with C. rectus and P. gingivalis significantly reduced the overall fecundity compared to controls (16.7% vs. 75%, infected vs. non-infected mice respectively, P = 0.03, Kaplan-Meier). The results supported an enhanced placental TLR4 expression after oral infection with periodontal pathogens. The TLR4 pathway has been implicated in the pathogenesis of preterm births; therefore the abnormal regulation of placental TLR4 may give new insights into how maternal periodontitis and periodontal pathogens might be linked to placental inflammation and preterm birth pathogenesis.

AB - Maternal periodontitis has emerged as a putative risk factor for preterm births in humans. The periodontitis-associated dental biofilm is thought to serve as an important source of oral bacteria and related virulence factors that hematogenously disseminate and affect the fetoplacental unit; however the underlying biological mechanisms are yet to be fully elucidated. This study hypothesized that an oral infection with the human periodontal pathogens Campylobacter rectus and Porphyromonas gingivalis is able to induce fetal growth restriction, placental inflammation and enhance Toll-like receptors type 4 (TLR4) expression in a murine pregnancy model. Female Balb/C mice (n = 40) were orally infected with C. rectus and/or P. gingivalis over a 16-week period and mated once/week. Pregnant mice were sacrificed at embryonic day (E) 16.5 and placentas were collected and analyzed for TLR4 mRNA levels and qualitative protein expression by real-time PCR and immunofluorescence. TLR4 mRNA expression was found to be increased in the C. rectus-infected group (1.98 ± 0.886-fold difference, P < 0.01, ANOVA) compared to controls. Microscopic analysis of murine placentas showed enhanced immunofluorescence of TLR4 in trophoblasts, mainly in the placental labyrinth layer. Also, combined oral infection with C. rectus and P. gingivalis significantly reduced the overall fecundity compared to controls (16.7% vs. 75%, infected vs. non-infected mice respectively, P = 0.03, Kaplan-Meier). The results supported an enhanced placental TLR4 expression after oral infection with periodontal pathogens. The TLR4 pathway has been implicated in the pathogenesis of preterm births; therefore the abnormal regulation of placental TLR4 may give new insights into how maternal periodontitis and periodontal pathogens might be linked to placental inflammation and preterm birth pathogenesis.

KW - Campylobacter rectus

KW - Mice

KW - Periodontitis

KW - Placenta

KW - Porphyromonas gingivalis

KW - Preterm birth

KW - Toll-like receptors

UR - http://www.scopus.com/inward/record.url?scp=58249090754&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58249090754&partnerID=8YFLogxK

U2 - 10.1016/j.placenta.2008.11.017

DO - 10.1016/j.placenta.2008.11.017

M3 - Article

C2 - 19101032

AN - SCOPUS:58249090754

VL - 30

SP - 156

EP - 162

JO - Placenta

JF - Placenta

SN - 0143-4004

IS - 2

ER -