Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Am J Reprod Immunol. 2020 Jul;84(1):e13248. doi: 10.1111/aji.13248. Epub 2020 May 22.
Systemic maternal inflammation is associated with adverse neonatal sequelae. We tested the hypothesis that IL-1β is a key inflammatory regulator of adverse pregnancy outcomes.
Pregnant mice were treated with intraperitoneal injections of IL-1β (0, 0.1, 0.5, or 1 μg) from embryonic day (E)14 to E17. Placenta and fetal brains were harvested and analyzed for morphologic changes and IL-1β signaling markers.
As compared with non-treated dams, maternal injections with IL-1β resulted in increased p-NF-κB and caspase-1 in placentas and fetal brains, but not consistently in spleens, suggesting induction of intrinsic IL-1β production. These findings were confirmed by increased levels of IL-1β in the placentas of the IL-1β-treated dams. Systemic treatment of dams with IL-1β suppressed Stat1 signaling. Maternal inflammation caused by IL-1β treatment reduced fetal viability to 80.6% and 58.9%, in dams treated with either 0.5 or 1 μg of IL-1β, respectively. In the placentas, there was an IL-1β dose-dependent distortion of the labyrinth structure, decreased numbers of mononuclear trophoblast giant cells, and reduced proportions of endothelial cells as compared to placentas from control dams. In fetal brains collected at E17, there was an IL-1β dose-dependent reduction in cortical neuronal morphology.
This work demonstrates that systemic IL-1β injection causes dose-dependent structural and functional changes in the placenta and fetal brain.
全身性母体炎症与不良新生儿后遗症有关。我们检验了这样一个假设，即白细胞介素-1β（IL-1β）是调节不良妊娠结局的关键炎症调节因子。
从胚胎第 14 天（E）到第 17 天，给怀孕的老鼠腹膜内注射 IL-1β（0、0.1、0.5 或 1μg）。采集胎盘和胎儿大脑进行形态学变化和 IL-1β信号标志物分析。
与未经处理的母鼠相比，IL-1β 母鼠注射导致胎盘和胎儿大脑中的 p-NF-κB 和 caspase-1 增加，但脾脏中并未持续增加，提示内源性 IL-1β 产生的诱导。这些发现通过 IL-1β 处理母鼠胎盘内 IL-1β 水平的增加得到了证实。母鼠全身给予 IL-1β 会抑制 Stat1 信号。IL-1β 处理引起的母体炎症分别使接受 0.5μg 和 1μg IL-1β 处理的母鼠的胎儿存活率降低到 80.6%和 58.9%。在胎盘方面，与对照组相比，IL-1β 处理剂量依赖性地破坏了合体滋养层结构，单核滋养层巨细胞数量减少，内皮细胞比例降低。在 E17 时收集的胎儿大脑中，皮质神经元形态存在剂量依赖性的 IL-1β 减少。
这项工作表明，全身注射 IL-1β 会导致胎盘和胎儿大脑的结构和功能发生剂量依赖性变化。
