Maternal Smoking Dysregulates Protein Expression in Second Trimester Human Fetal Livers in a Sex-Specific Manner
Maternal Smoking Dysregulates Protein Expression in Second Trimester Human Fetal Livers in a Sex-Specific Manner
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DOI：
10.1210/jc.2014-3941
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发表时间：
2015-06-01
影响因子：
5.8
通讯作者：
Fowler, Paul A.
中科院分区：
文献类型：
--
作者：
Filis, Panagiotis;Nagrath, Nalin;Fowler, Paul A.
内容：母亲在怀孕期间吸烟对后代有不良影响目的：我们的目的是首次分析人类胎儿肝脏蛋白质组，以确定受母亲吸烟影响的途径。设计：从选择性中期妊娠终止中提取的胎肝蛋白（12-16周妊娠）根据性别和母亲吸烟情况分为四个平衡组。收集24个形态正常的胎儿进行终止非医疗原因和分析在阿伯丁大学和格拉斯哥。主要结果Measures：蛋白提取物进行了解决的2D-PAGE和SameSpots软件进行了分析。免疫途径分析被用来调查可能的作用，通过串联液相色谱/质谱鉴定的失调蛋白质。结果：一个或多个组（胎儿性别和/或母亲吸烟）之间的显着表达差异被发现在22个蛋白点。母亲吸烟影响蛋白质的翻译后蛋白质加工和分泌（ERP 29，PDIA 3），应激反应和解毒（HSP 90 AA 1，HSBP 1，ALDH 7A 1，CAT），和稳态（FTL 1，ECHS 1，GLUD 1，AFP，SDHA）的作用。虽然参与坏死和癌症发展的蛋白质在两种性别的影响，影响细胞内稳态，炎症，增殖和凋亡的途径在男性和途径影响葡萄糖代谢的影响在femines.Conclusions：胎儿肝脏表现出显着的性别差异在蛋白质水平上，这些都受到母亲吸烟。吸烟引起的产后疾病的基础很可能是由于不同途径的性别特异性影响。
Context: Maternal smoking during pregnancy has adverse effects on the offspring (eg, increased likelihood of metabolic syndrome and infertility), which may involve alterations in fetal liver function.Objective: Our aim was to analyze, for the first time, the human fetal liver proteome to identify pathways affected by maternal smoking.Design: Fetal liver proteins extracted from elective second trimester pregnancy terminations (12-16 weeks of gestation) were divided in four balanced groups based on sex and maternal smoking.Setting and Participants: Livers were collected from 24 morphologically normal fetuses undergoing termination for nonmedical reasons and analyzed at the Universities of Aberdeen and Glasgow.Main Outcome Measures: Protein extracts were resolved by 2D-PAGE and analyzed with SameSpots software. Ingenuity pathway analysis was used to investigate likely roles of dysregulated proteins identified by tandem liquid chromatography/ mass spectroscopy.Results: Significant expression differences between one or more groups (fetal sex and/or maternal smoking) were found in 22 protein spots. Maternal smoking affected proteins with roles in post-translational protein processing and secretion (ERP29, PDIA3), stress responses and detoxification (HSP90AA1, HSBP1, ALDH7A1, CAT), and homeostasis (FTL1, ECHS1, GLUD1, AFP, SDHA). Although proteins involved in necrosis and cancer development were affected in both sexes, pathways affecting cellular homeostasis, inflammation, proliferation, and apoptosis were affected in males and pathways affecting glucose metabolism were affected in females.Conclusions: The fetal liver exhibits marked sex differences at the protein level, and these are disturbed by maternal smoking. The foundations for smoke-induced post-natal diseases are likely to be due to sex-specific effects on diverse pathways.