title: Abnormal pregnancy outcomes in mice using an induced periodontitis model and the haematogenous migration of Fusobacterium nucleatum sub-species to the murine placenta.
abstract: OBJECTIVE
  To investigate if there is subspecies specific migration to the placenta by Fusobacterium nucleatum (Fn) and to determine whether experimentally induced periodontitis results in adverse pregnancy outcomes (APO) in mice.
  
  
  METHODS
  Periodontitis was induced in pregnant mice using an inoculum of Fn and Porphyromonas gingivalis. In parallel, four sub-species of Fn were individually injected into the circulatory system. At day 18 of gestation, the placenta, liver, spleen and blood were harvested and litter size, number of viable fetuses and resorptions, maternal, fetal and placenta weights were recorded. For the direct inoculation group, some mice were allowed to deliver for assessment of length of gestation, litter size, maternal, placental and pup weight. The presence of Fn was assessed by PCR and inflammatory mediators were measured by ELISA or multiplex analysis.
  
  
  RESULTS
  Mice with alveolar bone loss, a marker of periodontitis, demonstrated significantly higher fetal weights (p = 0.015) and fetal/placental weight ratios (p = 0.030). PCR analysis of maternal organs did not identify Fn in any extracted tissues. In mice that received direct injection of Fn subspecies, varying degrees of APO were observed including preterm birth, intrauterine growth restriction, and fetal loss. Haematogenous spread of only Fn subsp. nucleatum to the placenta was confirmed. Litter size was significantly smaller (p = 0.023) and the number of resorptions was higher in inoculated versus control groups. Mice injected with subsp. nucleatum had significantly increased circulating CRP levels (p = 0.020) compared to controls while the mice with induced periodontitis had increased levels of IL-6 (p = 0.047) and IL-8 (p = 0.105).
  
  
  CONCLUSIONS
  Periodontitis in mice elevated fetal weight and the fetal weight/placental weight ratio. This study found that subsp. nucleatum migrated haematogenously to the placenta, leading to APO in mice. The study supports the potential role of Fn in the association between periodontitis and APO.
authors: Oral Microbiology, School of Dentistry, The University of Adelaide, Adelaide, Australia.
authors: Sara
authors: S
authors: Stockham
authors: Oral Microbiology, School of Dentistry, The University of Adelaide, Adelaide, Australia.
authors: Justine E
authors: JE
authors: Stamford
authors: Robinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia.
authors: Claire T
authors: CT
authors: Roberts
authors: Colgate Australian Clinical Dental Research Centre, School of Dentistry, The University of Adelaide, Adelaide, Australia.
authors: Tracy R
authors: TR
authors: Fitzsimmons
authors: Colgate Australian Clinical Dental Research Centre, School of Dentistry, The University of Adelaide, Adelaide, Australia.
authors: Ceilidh
authors: C
authors: Marchant
authors: Colgate Australian Clinical Dental Research Centre, School of Dentistry, The University of Adelaide, Adelaide, Australia.
authors: P Mark
authors: PM
authors: Bartold
authors: Oral Microbiology, School of Dentistry, The University of Adelaide, Adelaide, Australia.
authors: Peter S
authors: PS
authors: Zilm
mesh_terms: D016301:Alveolar Bone Loss / Q000000981:diagnostic imaging / Q000473:pathology; D000818:Animals; D002097:C-Reactive Protein / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D016967:Fusobacterium nucleatum / Q000235:genetics / Q000472:pathogenicity*; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D010518:Periodontitis / Q000382:microbiology / Q000473:pathology*; D010920:Placenta / Q000378:metabolism / Q000382:microbiology*; D016133:Polymerase Chain Reaction; D017861:Porphyromonas / Q000235:genetics / Q000472:pathogenicity; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000382:microbiology / Q000473:pathology*; D011256:Pregnancy Outcome; D012336:RNA, Ribosomal, 16S / Q000032:analysis; D011859:Radiography
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; D012336:RNA, Ribosomal, 16S; D002097:C-Reactive Protein