Placental programming of anxiety in adulthood revealed by Igf2-null models
Placental programming of anxiety in adulthood revealed by Igf2-null models
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DOI：
10.1038/ncomms3311
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发表时间：
2013-08-01
影响因子：
16.6
通讯作者：
Humby, Trevor
中科院分区：
文献类型：
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作者：
Mikaelsson, Mikael Allan;Constancia, Miguel;Humby, Trevor
印记的、母体沉默的胰岛素样生长因子-2在胎儿和胎盘中表达，并已在动物模型中显示在胎儿和胎盘发育中起作用。在这里，我们将胎盘特异性P0转录物（胰岛素样生长因子-2-P0 KO）被设计为零的小鼠与所有四种胰岛素样生长因子-2转录物均被破坏的小鼠进行了比较，因此胎盘和胎儿中的胰岛素样生长因子-2均为零（胰岛素样生长因子-2-总KO）。这两种模型都导致宫内生长受限，但在胎儿需求和胎盘营养供应之间存在不平衡的情况（胰岛素样生长因子-2-P0 KO）和需求和供应更平衡的情况（胰岛素样生长因子-2-总KO）之间存在分离。对焦虑刺激的反应性增加，只在妊娠期间胎盘供应与胎儿营养需求不匹配的动物中表现出来。我们的研究结果进一步区分胎盘功能障碍和宫内生长受限，并揭示了胎盘在长期情绪行为规划中的作用。
Imprinted, maternally silenced insulin-like growth factor-2 is expressed in both the foetus and placenta and has been shown to have roles in foetal and placental development in animal models. Here we compared mice engineered to be null for the placenta-specific P0 transcript (insulin-like growth factor-2-P0 KO) to mice with disruptions of all four insulin-like growth factor-2 transcripts, and therefore null for insulin-like growth factor-2 in both placenta and foetus (insulin-like growth factor-2-total KO). Both models lead to intrauterine growth restriction but dissociate between a situation where there is an imbalance between foetal demand and placental supply of nutrients (the insulin-like growth factor-2-P0 KO) and one where demand and supply is more balanced (the insulin-like growth factor-2-total KO). Increased reactivity to anxiety-provoking stimuli is manifested later in life only in those animals where there is a mismatch between placental supply and foetal demand for nutrients during gestation. Our findings further distinguish placental dysfunction from intrauterine growth restriction and reveal a role for the placenta in long-term programming of emotional behaviour.