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Infection and Immunity, September 2003, p. 5156-5162, Vol. 71, No. 9
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.9.5156-5162.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Porphyromonas gingivalis Infection during Pregnancy Increases Maternal Tumor Necrosis Factor Alpha, Suppresses Maternal Interleukin-10, and Enhances Fetal Growth Restriction and Resorption in Mice

Center for Oral and Systemic Diseases,¹ Comprehensive Center for Inflammatory Disorders, Department of Dental Ecology, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina,³ Environmental Health Science Department, University of Georgia, Athens, Georgia²

Received 19 December 2002/ Returned for modification 12 March 2003/ Accepted 20 June 2003

Epidemiological studies have shown a potential association between maternal periodontitis and pregnancy complications. We used a pregnant murine model to study the effect of infection with the periodontal pathogen Porphyromonas gingivalis on pregnancy outcomes. Female BALB/c mice were inoculated with heat-killed P. gingivalis (10⁹ CFU) in a subcutaneous chamber and mated 2 weeks later. At gestation day (GD) 7.5, mice were challenged with live P. gingivalis (10⁷ CFU) (n = 20) or broth (control; n = 8) and sacrificed at GD 16.5. Fetal growth restriction (FGR, <0.46 g) was defined as fetuses with weights 2 standard deviations (SD) smaller than controls (0.56 ± 0.05 g [mean ± SD]). Among the 20 challenged mice, 8 had both normal-weight (0.51 ± 0.11 g) and FGR (0.34 ± 0.1 g) fetuses within the same litter. All other challenged dams had normal-weight fetuses (0.57 ± 0.04 g). Maternal liver, uterus, and spleen samples were examined for P. gingivalis DNA using a PCR technique. Of the eight challenged mice with FGR fetuses, three had PCR signals for P. gingivalis in liver and uterus, but not in the spleen. Liver, uterus, and spleen were negative for P. gingivalis DNA among all other challenged and control mice. In serum of dams with FGR fetuses, tumor necrosis factor alpha levels were elevated significantly, while interluekin-10 levels were significantly reduced compared to levels in dams with normal fetuses. P. gingivalis-specific serum immunoglobulin G levels were significantly elevated in dams with FGR fetuses compared to dams without any FGR fetuses. These data demonstrate that P. gingivalis-induced murine FGR is associated with systemic dissemination of the organism and activated maternal immune and inflammatory responses.

Editor: J. N. Weiser

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