Department of Obstetrics and Gynecology, Maternal and Child Health Research Center, Center for Research on Reproduction and Women's Health, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Am J Reprod Immunol. 2019 Dec;82(6):e13189. doi: 10.1111/aji.13189. Epub 2019 Sep 30.
Exposure to intrauterine inflammation (IUI) has been shown to induce fetal brain injury and increase the risk of acquiring a neurobehavioral disorder. The trafficking of the inflammatory mediator, lipopolysaccharide (LPS), in the pregnant female reproductive tract in the setting of IUI and the precise mechanisms by which inflammation induces fetal brain injury are not fully understood.
FITC-labeled LPS was utilized to induce IUI on E15, tissues were collected, and fluorescence was visualized via the Spectrum IVIS. Embryo transfer was utilized to create divergent maternal and fetal genotypes. Wild-type (WT) embryos were transferred into TLR4-/- pseudopregnant dams (TLR4-/- /WT ). On E15, TLR4-/- /WT dams or their WT controls (WT /WT ) received an intrauterine injection of LPS or phosphate-buffered saline (PBS). Endotoxin and IL-6 levels were assessed in amniotic fluid, and cytokine expression was measured via QPCR.
Lipopolysaccharide trafficked to the uterus, fetal membranes, placenta, and the fetus and was undetectable in other tissues. Endotoxin was present in the amniotic fluid of all animals exposed to LPS. However, the immune response was blunted in TLR4-/- /WT compared with WT controls.
Intrauterine administered LPS is capable of accessing the entire feto-placental unit with or without a functional maternal TLR4. Thus, bacteria or bacterial byproducts in the uterus may negatively impact fetal development regardless of the maternal genotype or endotoxin response. Despite the blunted immune response in the TLR4-deficient dams, an inflammatory response is still ignited in the amniotic cavity and may negatively impact the fetus.
宫内炎症（IUI）暴露已被证明会导致胎儿脑损伤，并增加获得神经行为障碍的风险。在 IUI 情况下，炎症介质脂多糖（LPS）在孕妇生殖道中的转运以及炎症引起胎儿脑损伤的确切机制尚不完全清楚。
使用 FITC 标记的 LPS 在 E15 诱导 IUI，收集组织，并通过 Spectrum IVIS 可视化荧光。胚胎转移用于创建不同的母体和胎儿基因型。将野生型（WT）胚胎转移到 TLR4-/-假孕母鼠（TLR4-/-/WT）中。在 E15 时，TLR4-/-/WT 母鼠或其 WT 对照（WT/WT）接受宫内 LPS 或磷酸盐缓冲盐水（PBS）注射。评估羊水中的内毒素和 IL-6 水平，并通过 QPCR 测量细胞因子表达。
LPS 转运到子宫、胎膜、胎盘和胎儿，在其他组织中无法检测到。所有接受 LPS 暴露的动物的羊水均存在内毒素。然而，与 WT 对照相比，TLR4-/-/WT 的免疫反应减弱。
宫内给予 LPS 能够进入整个胎-胎盘单位，无论母体 TLR4 是否存在功能。因此，子宫内的细菌或细菌产物可能会对胎儿发育产生负面影响，而不管母体基因型或内毒素反应如何。尽管 TLR4 缺陷母鼠的免疫反应减弱，但仍会在羊水中引发炎症反应，可能对胎儿产生负面影响。
