Placental Malaria-Associated Inflammation Disturbs the Insulin-like Growth Factor Axis of Fetal Growth Regulation
Placental Malaria-Associated Inflammation Disturbs the Insulin-like Growth Factor Axis of Fetal Growth Regulation
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DOI：
10.1093/infdis/jiq080
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发表时间：
2011-02-15
影响因子：
6.4
通讯作者：
Rogerson, Stephen J.
中科院分区：
文献类型：
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作者：
Umbers, Alexandra J.;Boeuf, Philippe;Rogerson, Stephen J.
背景与胎盘疟疾相关的胎儿生长受限的发病机制在很大程度上是未知的。我们试图确定胎盘疟疾和相关炎症是否与胰岛素样生长因子（IGF）轴（胎儿生长的主要调节因子）紊乱有关。我们测量了88对分娩时母亲-新生儿血浆中的IGF-1和IGF-2浓度，并测量了巴布亚新几内亚一组患有和不患有胎盘疟疾的妇女脐带血浆中的IGF结合蛋白1和3（分别为IGFBP-1和IGFBP-3）。在配对的胎盘活检标本中检测IGF-1、IGF-2和IGF受体的信使RNA水平。与未感染的孕妇相比，患有胎盘恶性疟原虫感染和相关炎症的女性血浆样本中的IGF-1水平降低了28%（P = 0.007），其新生儿中的IGF-1水平降低了25%（P = 0.002）。与未感染的对照组相比，有炎症和无炎症的胎盘疟疾患者胎儿IGFBP-1水平升高（分别为P = 0.08和P = 0.006）。IGF-2和IGFBP-3血浆浓度和胎盘IGF配体和受体信使RNA转录水平在各组间相似。胎盘疟疾相关炎症干扰母体和胎儿IGF水平，IGF调节胎儿生长。这可能是胎盘疟疾导致胎儿生长受限的一种机制。
Background. The pathogenetic mechanisms of fetal growth restriction associated with placental malaria are largely unknown. We sought to determine whether placental malaria and related inflammation were associated with disturbances in the insulin-like growth factor (IGF) axis, a major regulator of fetal growth.Method. We measured IGF-1 and IGF-2 concentrations in plasma from 88 mother-neonate pairs at delivery and IGF binding proteins 1 and 3 (IGFBP-1 and IGFBP-3, respectively) in cord plasma from a cohort of Papua New Guinean women with and without placental malaria. Messenger RNA levels of IGF-1, IGF-2, and the IGF receptors were measured in matched placental biopsy specimens.Results. Compared with those for uninfected pregnancies, IGF-1 levels were reduced by 28% in plasma samples from women with placental Plasmodium falciparum infection and associated inflammation (P = .007) and by 25% in their neonates (P = .002). Levels of fetal IGFBP-1 were elevated in placental malaria with and without inflammation (P = .08 and P = .006, respectively) compared with uninfected controls. IGF-2 and IGFBP-3 plasma concentrations and placental IGF ligand and receptor messenger RNA transcript levels were similar across groups.Conclusion. Placental malaria-associated inflammation disturbs maternal and fetal levels of IGFs, which regulate fetal growth. This may be one mechanism by which placental malaria leads to fetal growth restriction.