title: Porphyromonas gingivalis infection during pregnancy increases maternal tumor necrosis factor alpha, suppresses maternal interleukin-10, and enhances fetal growth restriction and resorption in mice.
abstract: 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 (10(9) CFU) in a subcutaneous chamber and mated 2 weeks later. At gestation day (GD) 7.5, mice were challenged with live P. gingivalis (10(7) 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 interleukin-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.
authors.affiliation: Center for Oral and Systemic Diseases, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: Dongming
authors.initials: D
authors.lastname: Lin
authors.forename: Mary Alice
authors.initials: MA
authors.lastname: Smith
authors.forename: Catherine
authors.initials: C
authors.lastname: Champagne
authors.forename: John
authors.initials: J
authors.lastname: Elter
authors.forename: James
authors.initials: J
authors.lastname: Beck
authors.forename: Steven
authors.initials: S
authors.lastname: Offenbacher
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D016866:Bacteroidaceae Infections / Q000150:complications* / Q000276:immunology / Q000473:pathology; D001483:Base Sequence; D004269:DNA, Bacterial / Q000235:genetics / Q000302:isolation & purification; D004195:Disease Models, Animal; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology*; D005327:Fetal Resorption / Q000209:etiology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016753:Interleukin-10 / Q000378:metabolism*; D008099:Liver / Q000382:microbiology; D008431:Maternal-Fetal Exchange; D051379:Mice; D008807:Mice, Inbred BALB C; D016966:Porphyromonas gingivalis / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014599:Uterus / Q000382:microbiology
chemical_list: D000907:Antibodies, Bacterial; D004269:DNA, Bacterial; D007074:Immunoglobulin G; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10