Inflammation in rat pregnancy inhibits spiral artery remodeling leading to fetal growth restriction and features of preeclampsia.
Inflammation in rat pregnancy inhibits spiral artery remodeling leading to fetal growth restriction and features of preeclampsia.
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DOI：
10.1084/jem.20130295
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发表时间：
2014-01-13
期刊：
影响因子：
--
通讯作者：
Graham CH
中科院分区：
文献类型：
--
作者：
Cotechini T;Komisarenko M;Sperou A;Macdonald-Goodfellow S;Adams MA;Graham CH
异常的母体炎症导致TNF介导的胎儿生长受限和先兆子痫的一些特征，这些特征可以用一氧化氮模拟物硝酸甘油来改善。胎儿生长受限（FGR）和先兆子痫（PE）通常与母体异常炎症、螺旋动脉（SA）重构缺陷和子宫胎盘灌注改变有关。在这里，我们提供了一个新的机制之间的联系异常母体炎症和FGR的发展与PE的功能的证据。利用孕13.5-16.5天的孕鼠给予低剂量脂多糖（LPS）的模型，我们发现异常炎症导致由肿瘤坏死因子-α（TNF）介导的FGR。炎症也与滋养层浸润不足和SA重塑，以及改变子宫胎盘血流动力学和胎盘亚硝化应激有关。此外，炎症增加母体平均动脉压（MAP），并与肾结构改变和蛋白尿特征的PE。最后，透皮给药的一氧化氮（NO）模拟甘油三硝酸酯防止改变子宫胎盘灌注，LPS诱导的炎症，胎盘亚硝化应激，肾结构和功能的改变，MAP增加，和FGR。这些研究结果表明，母体炎症可通过一种涉及母体TNF水平升高的机制导致严重的妊娠并发症。我们的研究提供了一个理由，在治疗和/或预防炎症相关的妊娠并发症中使用的促炎剂或NO-模拟物。
Abnormal maternal inflammation leads to TNF-mediated fetal growth restriction and some features of preeclampsia that can be ameliorated with the nitric oxide mimetic nitroglycerin. Fetal growth restriction (FGR) and preeclampsia (PE) are often associated with abnormal maternal inflammation, deficient spiral artery (SA) remodeling, and altered uteroplacental perfusion. Here, we provide evidence of a novel mechanistic link between abnormal maternal inflammation and the development of FGR with features of PE. Using a model in which pregnant rats are administered low-dose lipopolysaccharide (LPS) on gestational days 13.5–16.5, we show that abnormal inflammation resulted in FGR mediated by tumor necrosis factor-α (TNF). Inflammation was also associated with deficient trophoblast invasion and SA remodeling, as well as with altered uteroplacental hemodynamics and placental nitrosative stress. Moreover, inflammation increased maternal mean arterial pressure (MAP) and was associated with renal structural alterations and proteinuria characteristic of PE. Finally, transdermal administration of the nitric oxide (NO) mimetic glyceryl trinitrate prevented altered uteroplacental perfusion, LPS-induced inflammation, placental nitrosative stress, renal structural and functional alterations, increase in MAP, and FGR. These findings demonstrate that maternal inflammation can lead to severe pregnancy complications via a mechanism that involves increased maternal levels of TNF. Our study provides a rationale for the use of antiinflammatory agents or NO-mimetics in the treatment and/or prevention of inflammation-associated pregnancy complications.
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