Dose-dependent structural and immunological changes in the placenta and fetal brain in response to systemic inflammation during pregnancy.
Dose-dependent structural and immunological changes in the placenta and fetal brain in response to systemic inflammation during pregnancy.
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DOI：
10.1111/aji.13248
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发表时间：
2020-07
期刊：
影响因子：
--
通讯作者：
Burd I
中科院分区：
文献类型：
--
作者：
Chudnovets A;Lei J;Na Q;Dong J;Narasimhan H;Klein SL;Burd I
母体全身炎症与新生儿不良后遗症有关。我们检验了 IL-1β 是不良妊娠结局的关键炎症调节因子的假设。从胚胎期 (E)14 至 E17，对怀孕小鼠进行腹腔注射 IL-1β（0、0.1、0.5 或 1 μg）。收获胎盘和胎儿大脑并分析形态变化和 IL-1β 信号标记。与未治疗的母鼠相比，母体注射 IL-1β 导致胎盘和胎儿脑中 p-NF-κB 和 caspase-1 增加，但在脾脏中不一致，表明诱导了内在 IL-1β 的产生。这些发现得到了 IL-1β 处理母鼠胎盘中 IL-1β 水平升高的证实。用 IL-1β 对母鼠进行全身治疗可抑制 Stat1 信号传导。在用 0.5 或 1 μg IL-1β 处理的母鼠中，IL-1β 处理引起的母体炎症使胎儿存活率分别降低至 80.6% 和 58.9%。与对照母鼠的胎盘相比，胎盘中迷路结构存在 IL-1β 剂量依赖性扭曲，单核滋养层巨细胞数量减少，内皮细胞比例减少。在 E17 收集的胎儿大脑中，皮质神经元形态出现 IL-1β 剂量依赖性减少。这项工作表明，全身性 IL-1β 注射会导致胎盘和胎儿大脑发生剂量依赖性结构和功能变化。
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.
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DOI：
10.4049/jimmunol.1601179
发表时间：
2017-01-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Brien ME;Duval C;Palacios J;Boufaied I;Hudon-Thibeault AA;Nadeau-Vallée M;Vaillancourt C;Sibley CP;Abrahams VM;Jones RL;Girard S
通讯作者：
Girard S
影响因子：
4.2
作者：
Bell, MJ;Hallenbeck, JM
通讯作者：
Hallenbeck, JM
影响因子：
2.5
作者：
CARNEY, EW;PRIDEAUX, V;ROSSANT, J
通讯作者：
ROSSANT, J
DOI：
10.1165/rcmb.2006-0116oc
发表时间：
2007-01-01
影响因子：
6.4
作者：
Bry, Kristina;Whitsett, Jeffrey A.;Lappalainen, Urpo
通讯作者：
Lappalainen, Urpo
影响因子：
9.8
作者：
Burd, Inna;Chai, Jinghua;Elovitz, Michal A.
通讯作者：
Elovitz, Michal A.