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Objectives  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.

plos one

Abnormal Pregnancy Outcomes in Mice Using an Induced Periodontitis Model and the Haematogenous Migration of Fusobacterium nucleatum Sub-Species to the Murine Placenta