Porphyromonas gingivalis infection during pregnancy increases maternal tumor necrosis factor alpha, suppresses maternal interleukin-10, and enhances fetal growth restriction and resorption in mice
Porphyromonas gingivalis infection during pregnancy increases maternal tumor necrosis factor alpha, suppresses maternal interleukin-10, and enhances fetal growth restriction and resorption in mice
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DOI：
10.1128/iai.71.9.5156-5162.2003
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发表时间：
2003-09-01
影响因子：
3.1
通讯作者：
Offenbacher, S
中科院分区：
文献类型：
--
作者：
Lin, DM;Smith, MA;Offenbacher, S
流行病学研究表明，产妇牙周炎和妊娠并发症之间存在潜在的关联。我们使用妊娠小鼠模型来研究牙周病原体牙龈卟啉单胞菌感染对妊娠结局的影响。雌性BALB/c小鼠皮下接种热灭活的牙龈卟啉单胞菌（10（9）CFU），2周后交配。在妊娠第7.5天（GD），用活牙龈卟啉单胞菌（10（7）CFU）（n = 20）或肉汤（对照; n = 8）攻击小鼠，并在GD 16.5处死。胎儿生长受限（FGR，< 0.46 g）定义为体重比对照组（0.56 +/- 0.05 g [平均值+/- SD]）小2个标准差（SD）的胎儿。在20只激发小鼠中，8只在同一窝中具有正常体重（0.51 +/- 0.11 g）和FGR（0.34 +/- 0.1 g）胎仔。所有其他攻毒母鼠的胎仔体重正常（0.57 ± 0.04 g）。使用PCR技术检查母体肝脏、子宫和脾脏样品的牙龈卟啉单胞菌DNA。在8只具有FGR胎儿的激发小鼠中，3只在肝脏和子宫中具有牙龈卟啉单胞菌的PCR信号，但在脾脏中没有。在所有其他激发和对照小鼠中，肝脏、子宫和脾脏的牙龈卟啉单胞菌DNA均为阴性。在FGR胎儿母鼠的血清中，与正常胎儿母鼠的水平相比，肿瘤坏死因子α水平显著升高，而白细胞介素-10水平显著降低。与没有任何FGR胎儿的母鼠相比，FGR胎儿母鼠的牙龈卟啉单胞菌特异性血清免疫球蛋白G水平显著升高。这些数据表明，牙龈卟啉单胞菌诱导的鼠FGR与生物体的全身传播和激活的母体免疫和炎症反应有关。
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 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.