Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, United States of America.
PLoS One. 2013 Aug 14;8(8):e72601. doi: 10.1371/journal.pone.0072601. eCollection 2013.
Gravid mice and other rodents inoculated with Listeria monocytogenes typically fail to clear an intrauterine infection and either succumb or expel their intrauterine contents. We took advantage of this property to investigate the effects of an extrauterine infection on parameters of pregnancy success. Pregnant mice were selected for our study if they showed no clinical signs of listeriosis following oral inoculation at 7.5 gestational days (gd), and had no detectable intrauterine colony forming units (cfu) at near term (18.5 gd). The range of oral doses employed was 10⁶-10⁸ cfu per mouse for two listerial serotype strains (4nonb and 1/2a). At all doses, inoculation resulted in a decrease in average near-term (18.5 gd) fetal weight per litter compared to sham inoculated controls. Additionally, embryonic death (indicated by intrauterine resorptions) was exhibited by some inoculated mice but was absent in all sham inoculated animals. In parallel experiments designed to detect possible loss of placental function, gravid uteruses were examined histopathologically and microbiologically 96 h after oral inoculation. Placental lesions were associated with high (> 10⁶), but not low (< 10²) or absent intrauterine cfu. In vitro, mouse embryonic trophoblasts were indistinguishable from mouse enterocytes in terms of their sensitivity to listerial exposure. A model consistent with our observations is one in which products (host or bacterial) generated during an acute infection enter embryos transplacentally and influences embryonic survival and slows normal growth in utero.
感染李斯特菌的妊娠小鼠和其他啮齿动物通常无法清除子宫内感染,要么死亡,要么排出子宫内的内容物。我们利用这一特性来研究子宫外感染对妊娠成功参数的影响。如果在 7.5 天的妊娠期经口接种后,怀孕的小鼠没有出现李斯特菌病的临床症状,并且在接近分娩时(18.5 天)没有检测到宫内集落形成单位(cfu),则选择它们进行我们的研究。我们使用的口服剂量范围为每只小鼠 10⁶-10⁸ cfu 两种李斯特菌血清型菌株(4nonb 和 1/2a)。在所有剂量下,与假接种对照组相比,接种导致平均近(18.5 天)胎鼠体重每窝降低。此外,一些接种小鼠表现出胚胎死亡(由宫内吸收表示),而所有假接种动物均未表现出这种情况。在设计用于检测胎盘功能可能丧失的平行实验中,在经口接种后 96 小时检查妊娠子宫的组织病理学和微生物学。胎盘病变与高(> 10⁶)而不是低(< 10²)或不存在宫内 cfu 相关。在体外,小鼠胚胎滋养层在对李斯特菌暴露的敏感性方面与小鼠肠细胞没有区别。与我们的观察结果一致的模型是,在急性感染期间产生的产物(宿主或细菌)经胎盘进入胚胎,并影响胚胎存活并减缓宫内正常生长。