The effects of intra-amniotic injection of periodontopathic lipopolysaccharides in sheep

• Published in: American journal of obstetrics and gynecology 2005-08, Vol.193 (2), p.313-321
• Main Authors: Newnham, John P., Shub, Alexis, Jobe, Alan H., Bird, Philip S., Ikegami, Machiko, Nitsos, Ilias, Moss, Timothy J.M.
• Format: Article
• Language: English
• Subjects: Acid-Base Equilibrium; Aggregatibacter actinomycetemcomitans; Amniotic Fluid - microbiology; Animals; Escherichia coli; Female; Fetal Blood - microbiology; Fetal Death - etiology; Fusobacterium nucleatum; Lipopolysaccharides - administration & dosage; Periodontal Diseases - complications; Periodontal Diseases - microbiology; Periodontopathic lipopolysaccharide; Porphyromonas gingivalis; Pregnancy; Pregnancy Complications - microbiology; Random Allocation; Sheep
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/j.ajog.2005.03.065

Periodontal disease may cause several complications of pregnancy, including fetal death. The purpose of this study was to investigate in sheep the effects of the intra-amniotic injection of lipopolysaccharide from 3 periodontopathic organisms and to compare these effects with those resulting from similar injection of Escherichia coli lipopolysaccharide. The outcomes that were studied included the rates of fetal death and the features of inflammation and lung maturation in survivors. At 118 days of pregnancy, ewes that were bearing single fetuses were allocated at random to receive intra-amniotic injections of saline solution (n = 13 fetuses), or lipopolysaccharide from Porphyromonas gingivalis (in doses from 0.1 to 10 mg [n = 22 fetuses]), Actinobacillus actinomycetemcomitans (10 mg [n = 6 fetuses]; 1 mg [n = 6 fetuses]), Fusobacterium nucleatum (10 mg [n = 6 fetuses]) or Escherichia coli (10 mg [n = 14 fetuses]; 1 mg [n = 7 fetuses]). Surviving fetuses were delivered abdominally at 125 days of gestation (term, 150 days). When compared with Escherichia coli lipopolysaccharide at similar dosages, periodontopathic lipopolysaccharides had high rates of fetal lethality. Only 6 of 22 fetuses that were exposed to intra-amniotic Porphyromonas gingivalis lipopolysaccharide survived doses of 0.1 to 10 mg, and only 3 of 6 fetuses survived 10-mg Actinobacillus actinomycetemcomitans lipopolysaccharide. Escherichia coli lipopolysaccharide did not cause fetal loss when given at doses of 10 mg (n = 14 fetuses) or 1 mg (n = 7 fetuses). Fetuses that survived exposure to these lipopolysaccharides showed features of inflammation in amniotic fluid and cord blood at birth and enhanced lung maturation. Lipopolysaccharides from these 3 periodontopathic organisms have much higher rates of fetal lethality than Escherichia coli lipopolysaccharide but can cause similar intrauterine inflammatory responses and improvements in lung volumes in survivors. Sources of inflammation that are distant from the uterus may underlie a proportion of unexplained stillbirth and other complications of pregnancy.