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

Arce, R.M.; Barros, S.P.; Wacker, B.; Peters, B.; Moss, K.; Offenbacher, S.

doi:10.1016/j.placenta.2008.11.017

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Volume 30, Issue 2 , Pages 156-162, February 2009

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

R.M. Arce
- University of North Carolina at Chapel Hill, Center for Oral and Systemic Diseases, USA
S.P. Barros
- University of North Carolina at Chapel Hill, Center for Oral and Systemic Diseases, USA
- Department of Periodontology, UNC School of Dentistry, Chapel Hill, NC, USA
B. Wacker
- University of North Carolina at Chapel Hill, Center for Oral and Systemic Diseases, USA
B. Peters
- University of North Carolina at Chapel Hill, Center for Oral and Systemic Diseases, USA
K. Moss
- University of North Carolina at Chapel Hill, Center for Oral and Systemic Diseases, USA
- Department of Dental Ecology, UNC School of Dentistry, Chapel Hill, NC, USA
S. Offenbacher
- University of North Carolina at Chapel Hill, Center for Oral and Systemic Diseases, USA
- Department of Periodontology, UNC School of Dentistry, Chapel Hill, NC, USA
- Corresponding author. Center for Oral and Systemic Diseases, NC Oral Health Institute, School of Dentistry, University of North Carolina at Chapel Hill, 79 T.W. Alexander Drive, 4301 Research Commons, Research Triangle Park, NC 27709, USA. Tel.: +1 919 425 3596; fax: +1 919 425 3529.

Accepted 20 November 2008. published online 22 December 2008.

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