Prenatal air pollution exposure induces sexually dimorphic fetal programming of metabolic and neuroinflammatory outcomes in adult offspring
Prenatal air pollution exposure induces sexually dimorphic fetal programming of metabolic and neuroinflammatory outcomes in adult offspring
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DOI：
10.1016/j.bbi.2013.10.029
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发表时间：
2014-03-01
影响因子：
15.1
通讯作者：
Bilbo, Staci D.
中科院分区：
文献类型：
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作者：
Bolton, Jessica L.;Auten, Richard L.;Bilbo, Staci D.
在发育的关键时期，环境中的化学品暴露可能会导致肥胖症的流行率不断上升。我们测试了一个假设，即产前暴露于柴油机尾气颗粒（DEP），空气污染的主要组成部分，将长期引发小胶质细胞，导致成年后暴露于高脂肪饮食后代谢和情感结果加剧。同期交配的小鼠母鼠在整个妊娠期间间歇性地暴露于溶剂（VEH）或DEP的呼吸道滴注。成年雄性和雌性后代，然后喂养低脂肪饮食（LFD）或高脂肪饮食（HFD）9周。与VEH暴露母鼠的雄性后代相比，DEP暴露母鼠的雄性后代在HFD上表现出夸大的体重增加、胰岛素抵抗和焦虑样行为，而雌性后代在产前治疗方面没有差异。此外，HFD诱导两种性别动物脂肪组织和大脑巨噬细胞浸润的证据，但这些细胞在DEP/HFD雄性动物中更特异性地活化。DEP/HFD雄性动物在海马中还表达了显著更高水平的小胶质细胞/巨噬细胞，但不是星形胶质细胞活化标志物，而雌性动物仅表现出HFD对星形胶质细胞活化标志物的抑制。在第二个实验中，DEP雄性后代在出生后第30天（P）对LPS激发产生了过度的外周IL-1 β反应，而它们的中枢IL-1 β反应与VEH雄性后代没有差异，这表明由于产前DEP暴露导致巨噬细胞启动。总之，产前空气污染暴露“程序”后代增加易感性饮食诱导的代谢，行为和神经炎症变化在成年期的性二态的方式。(C)2013 Elsevier Inc. All rights reserved.
Environmental chemical exposures during critical windows of development may contribute to the escalating prevalence of obesity. We tested the hypothesis that prenatal exposure to diesel exhaust particles (DEP), a primary component of air pollution, would prime microglia long-term, resulting in exacerbated metabolic and affective outcomes following exposure to a high-fat diet in adulthood. Time-mated mouse dams were intermittently exposed to respiratory instillations of either vehicle (VEH) or DEP throughout gestation. Adult male and female offspring were then fed either a low-fat diet (LFD) or high-fat diet (HFD) for 9 weeks. The male offspring of DEP-exposed dams exhibited exaggerated weight gain, insulin resistance, and anxiety-like behavior on HFD compared to the male offspring of VEH-exposed dams, whereas female offspring did not differ according to prenatal treatment. Furthermore, HFD induced evidence of macrophage infiltration of both adipose tissue and the brain in both sexes, but these cells were more activated specifically in DEP/HFD males. DEP/HFD males also expressed markedly higher levels of microglial/macrophage, but not astrocyte, activation markers in the hippocampus, whereas females exhibited only a suppression of astrocyte activation markers due to HFD. In a second experiment, DEP male offspring mounted an exaggerated peripheral IL-1 beta response to an LPS challenge at postnatal day (P)30, whereas their central IL-1 beta response did not differ from VEH male offspring, which is suggestive of macrophage priming due to prenatal DEP exposure. In sum, prenatal air pollution exposure "programs" offspring for increased susceptibility to diet-induced metabolic, behavioral, and neuroinflammatory changes in adulthood in a sexually dimorphic manner. (C) 2013 Elsevier Inc. All rights reserved.